National Academies Press: OpenBook
« Previous: 1 HIV/AIDS in Injecting Drug Users
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

2
Treatment for Drug Dependence

The most effective way for IDUs to reduce their risk for contracting HIV through contaminated injecting equipment is to stop using drugs, and if that is not possible, to stop or reduce the frequency of injecting. Drug dependence treatment is therefore a critical HIV prevention strategy. It can interrupt HIV transmission by reducing drug-related HIV risk behavior, including frequency of drug use, injecting drug use, or sharing of injecting equipment. Although not the primary goal, drug treatment programs also have the potential to reduce risk behavior associated with the sexual transmission of HIV, such as sexual activity triggered by disinhibition or other drug effects, and engaging in sex in exchange for drugs or money. Beyond its effects on HIV transmission, drug dependence treatment can reduce other adverse health and social effects of drug abuse, including deaths from overdose and other drug-related causes of excess morbidity and mortality, and serve as an entry point into health and social services, including HIV/AIDS treatment (Sorenson and Copeland, 2000).

Drug dependence treatment can occur in a variety of settings, including inpatient, outpatient, and residential venues, and often blends different treatment approaches, including pharmacotherapy and psychosocial interventions. This chapter addresses the efficacy and effectiveness of pharmacotherapies—both agonist and antagonist agents for treating opioid1 depen-

1

“Opiates are a group of psychoactive substances derived from the poppy plant, that includes opium, morphine, codeine, and some others. The term ‘opiate’ is also used for the

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

dence, and pharmacotherapies for treating stimulant dependence (on cocaine or amphetamine-type drugs)—as well as psychosocial interventions. This chapter also examines the extent to which drug treatment provides IDUs with links to other health and social services.

The primary goal of drug abuse treatment is to reduce drug use. By doing so, it may also decrease injection drug use and other risk behaviors associated with drug use and provide a platform for providing other specific interventions directly targeting HIV transmission. Thus it may have direct, indirect, and facilitative effects on prevention of HIV transmission. As a result, the Committee first reviews the evidence regarding the effectiveness of drug treatment in reducing drug use and improving treatment-related outcomes, and then considers the impact of such treatment on HIV-related outcomes.

Efficacy refers to how well a treatment works under the best of circumstances, or in controlled clinical trials. Effectiveness refers to how well the treatment works in actual clinical practice. From a public health perspective, a particular treatment will have the greatest impact on HIV transmission if it is effective in reducing drug use and drug- and sex-related HIV risk behavior, and if it attracts and retains a large-enough proportion of drug-dependent individuals. Some treatments may be efficacious in controlled clinical trials but difficult to scale up for widespread, effective use in community settings. Other treatments may be efficacious but not attractive enough to patients to gain widespread acceptance. Although clinically efficacious treatments may reduce drug use and HIV transmission among drug-dependent patients who receive the treatment, unless these treatments are sufficiently widely disseminated, accessible, and attractive to the entire population of drug-dependent individuals, even the most efficacious treatment will not substantially reduce HIV transmission and other problems resulting from drug dependence in a country.

Social factors may also affect the willingness of drug-dependent patients to participate in efficacious treatments. Discrimination against patients receiving treatment for drug dependence and the stigma associated with drug dependence, as well as the monetary costs and other demands of treatment, can deter drug-dependent individuals from seeking or remaining

semisynthetic drug heroin that is produced from poppy compounds. The term ‘opioids’ refers to opiates and other semisynthetic and synthetic compounds with similar properties. Opioids are dependence producing substances, which elicit their effects by activating opioid receptors in the brain. Opioids are generally consumed by injection, oral ingestion or inhalation of the fumes produced by heating. Regular use of opioids can lead to opioid dependence” (WHO et al., 2004, p. 4).

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

in treatment (IOM, 1990). For drug abuse treatment to be most effective in reducing HIV transmission, it is essential that social policies encourage rather than discourage participation in treatment. In addition, consistent encouragement or even pressure to enter and remain in treatment from family members, friends, community leaders, or authorities can increase treatment engagement and contribute to successful treatment outcomes (IOM, 1990). The criminal justice system can also play an important role in getting drug users into treatment and outcomes by providing treatment as an alternative to incarceration, or as a condition of probation or parole (IOM, 1990).

THE COMMITTEE’S APPROACH TO EVALUATING THE STRENGTH OF THE EVIDENCE

A large number of systematic approaches to evaluating the quality and strength of scientific evidence are available. Many of these approaches, such as that used by the U.S. Preventive Services Task Force,2 rely on explicit criteria to assign a “grade” to the evidence. Others use a more qualitative approach. In evaluating the strength of the evidence on the effectiveness of HIV prevention strategies for IDUs, the Committee used a structured qualitative method based on an approach developed by the GRADE Working Group—a collaboration of researchers that aims to address problems with rating systems (GRADE Working Group, 2004).

The GRADE approach takes into account strength of study design, study quality, consistency of findings across studies, directness/relevance of outcome measures, and populations. In establishing causality, this approach grades randomized trials as strong, prospective cohort and case-control studies as moderate, and other observational studies and reports as modest (e.g., serial cross-sectional, ecologic) or weak (e.g., cross-sectional) (see Box 2.1 for a description of common research study designs). The approach downgrades studies for serious limitations on quality; important inconsistencies; sparse, indirect, or imprecise data; low follow-up rates; and a high probability of reporting bias. Studies are upgraded for strong evidence of an association, consistency of effect, demonstration of dose-response, and good analytic control of confounders. Combining these elements, the approach assigns evidence to one of four quality categories:

  • Strong: Further research is very unlikely to change confidence in the estimate of the effect.

2

The task force’s rating system for the strength of the evidence is available at: http://www.ahrq.gov/clinic/3rduspstf/ratings.htm.

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
  • Moderate: Further research is likely to have an important impact on confidence in the estimate of effect, and may change the estimate.

  • Modest: Further research is very likely to have an important impact on confidence in the estimate of effect, and likely to change the estimate.

  • Weak: Further research is very likely to change the estimate, and possibly the direction of a very uncertain estimate of effect.

The Committee considered other factors when rating the strength of evidence regarding an intervention. These included the total number of studies, their generalizability, the intervention’s applicability in practice, tradeoffs between benefits and harm, and acceptability to recipients. While considering all evidence as potentially policy relevant, the Committee sought to place greater weight on evidence of the highest quality in making its conclusions and recommendations.

EFFICACY AND EFFECTIVENESS OF PHARMACOTHERAPIES

This section first reviews evidence of effectiveness for opioid agonist therapies on (1) overall drug use and treatment-related outcomes; (2) drug-related HIV risk behavior; (3) sex-related HIV risk behavior; and (4) HIV incidence or seroconversion. The section considers factors that affect the impact of length of treatment, dosage, and adjunctive psychosocial therapy on the effectiveness of these treatments.

Opioid agonist medications have two primary clinical applications: they can be used on a limited basis to facilitate opioid detoxification,3 or they can be administered over a longer-period as a maintenance treatment (IOM, 1995). This report focuses on the latter application. The section also reviews evidence of unintended consequences of opioid agonist therapy, such as misuse and diversion of treatment medications into illicit channels. The section then examines evidence on the effectiveness of opioid antago-

3

Detoxification refers to medically supervised withdrawal from a substance until the person reaches a drug-free state. Pharmacological agents are often used during detoxification to alleviate client discomfort and to reduce potential complications. Opioid agonist medications can be used to help manage withdrawal symptoms during detoxification from opioids (IOM, 1990). When used to assist with detoxification, opioid agonist medications are provided tapered doses until the patient achieves a drug-free state (IOM, 1990, 1995). Detoxification alone is not considered an effective treatment (IOM, 1990). Studies show users have high rates of relapse to drug use when detoxification is not followed by further therapeutic intervention (IOM, 1990). Several other detoxification strategies can also be used including symptomatic treatment of withdrawal effects (e.g., with clonidine), or precipitated withdrawal without medication (IOM, 1995). This report does not address the relative advantages and disadvantages of these approaches.

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

BOX 2-1:

Definitions of Common Research Study Designs

Randomized control trial (RCT): An epidemiologic experiment in which subjects in a population are randomly allocated into groups, usually called “study” and “control” groups, to receive or not to receive an experimental preventive or therapeutic procedure, maneuver, or intervention. The results are assessed by rigorous comparison of rates of disease, death, recovery, or other appropriate outcome in the study and control groups, respectively. RCTs are generally regarded as the most scientifically rigorous method of hypothesis testing available in epidemiology.

Case-control study: A study that starts with the identification of persons with the disease (or other outcome variable) of interest, and a suitable control (comparison, reference) group of persons without the disease. The relationship of an attribute to the disease is examined by comparing the diseased and non-diseased with regard to how frequently the attribute is present or, if quantitative, the levels of the attributes, in each of the groups.

Cohort study: The analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of cohort study is observation of large numbers over a long period (commonly years) with comparison of incidence rates in groups that differ in exposure levels. The alternative terms for a cohort study, i.e., follow-up, longitudinal, and prospective study, describe an essential feature of the method, which is observation of the population for a sufficient number of person-years to generate reliable incidence or mortality rates in the population subsets. This generally implies study of a large population, study for a prolonged period (years), or both.

nist medication, which blocks the euphoric or rewarding effects of heroin or other opioids, and thus may help prevent resumption of opioid use. In addition, the Committee reviews the evidence of effectiveness for pharmacological treatments of stimulant dependence.

In reviewing pharmacological treatments for opioid and stimulant abuse, the Committee relied partly on several recent reviews and meta-analyses by the Cochrane Collaboration.4 The Committee also relied partly

4

The Cochrane Drugs and Alcohol Review Group is part of the Cochrane Collaboration, which was developed in the United Kingdom in 1992 with the goal of producing systematic reviews of the effects of various health care interventions that clinicians can use to guide their day-to-day practice. The review group conducts systematic reviews primarily of randomized clinical trials and controlled clinical trials of prevention, treatment, and rehabilitation interventions targeting drug dependence. The review group has published more than 30 reviews and 15 protocols. These are available at: http://alcalc.oxfordjournals.org/cgi/content/full/36/2/109; http://www.cochrane.org/newslett/DrugsandAlcoholAutumn2005.pdf.

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

Cross-sectional study: A study that examines the relationship between diseases (or other health-related characteristics) and other variables of interest as they exist in a defined population at one particular time. The presence or absence of disease and the presence or absence of the other variables (or, if they are quantitative, their level) are determined in each member of the study population or in a representative sample at one particular time. The relationship between a variable and the disease can be examined (1) in terms of the prevalence of disease in different population subgroups defined according to the presence or absence (or level) of the variables and (2) in terms of the presence or absence (or level) of the variables in the diseased vs. the non-diseased. Note that the disease prevalence rather than incidence is normally recorded in a cross-sectional study. The temporal sequence of cause and effect cannot necessarily be determined in a cross-sectional study.

Mathematical model: A representation of a system, process, or relationship in mathematical form in which equations are used to simulate the behavior of the system or process under study. The model usually consists of two parts: the mathematical structure itself, and the particular constants or parameters associated with them. A mathematical model is deterministic if the relations between the variables involved take on values not allowing for any play of chance. A model is said to be statistical, stochastic, or random, if random variation is allowed to enter the picture.

Ecological study: A study in which the units of analysis are populations or groups of people, rather than individuals. An ecological correlation is a correlation in which units studied are populations rather than individuals. Correlations found in this manner may not hold true for the individual members of these populations.

SOURCE: Verbatim definitions from A Dictionary of Epidemiology (Last, 1995).

on an earlier IOM report, Treating Drug Problems (1990). The Committee updated the search strategies used in the Cochrane reviews to identify critical studies published since those reviews occurred. (See Appendix B for more detail on the Committee’s review methodology.)

OPIOID AGONIST MAINTENANCE PHARMACOTHERAPY

Opioid agonist maintenance therapies prevent withdrawal symptoms, decrease craving, and—by creating cross-tolerance to these effects—block or diminish the effects of illicit opioid use. Use of these long-acting oral medications allows patients to stabilize physiologically so that they can reengage in normal life activities (WHO et al., 2004; IOM, 1990). Due to their long half life and resulting steady state, opioid agonists are not intoxicating and do not impair function when used at clinically appropriate and stable doses over time (IOM, 1990, 1995). This is a central phenomenon that distinguishes their therapeutic use from their misuse when injected,

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

and distinguishes agonist treatment agents from other opioids, such as heroin, that are misused for their consciousness-altering properties.

Many studies have examined the efficacy and effectiveness of opioid agonist maintenance therapies for treating opioid dependence. The Committee limited its review of evidence to the two most commonly used opioid agonist therapies, methadone and buprenorphine. Other pharmacological agonist agents have been used in some countries for both detoxification and maintenance therapy. Although many studies have demonstrated Levo-Alpha-Acetyl-Methadol’s (LAAM’s) effectiveness (see Clark et al., 2002) as a maintenance therapy for treating opioid dependence, reports of serious cardiac-related adverse events led to its withdrawal from the European market in 2001 (EMEA, 2001) and to extensive labeling changes for U.S. package inserts (U.S. FDA, 2001).5 Other opioid agonists, including prescription heroin (diacetylmorphine), tincture of opium, dihydrocodeine, and oral preparations of morphine, have been studied in limited settings but are not widely used (MacCoun and Reuter, 2001; WHO et al., 2004).

Effects on Drug Use and Treatment-Related Outcomes

A number of randomized clinical trials (RCTs) have shown the efficacy and effectiveness of methadone and buprenorphine maintenance therapies versus no opioid agonist treatment for drug and treatment-related outcomes. The evidence for each of these therapies is examined below.

Methadone

An extensive body of evidence spanning over three decades supports the efficacy of methadone maintenance as a treatment for opioid depen dence. In a recent Cochrane review (Mattick et al., 2003a), investigators conducted a meta-analysis of six RCTs comparing methadone maintenance treatment (MMT) with either placebo maintenance or other non-pharmacological therapy for heroin dependence.6 The six studies were conducted in diverse locations, including the United States, Sweden, Hong Kong, and Thailand. Two of the six trials were double-blinded and

5

Roxanne Laboratories, Inc., the manufacturer of ORLAAM ® (Levomethadyl hydrocholoride acetate) Oral Solution, 10 mg/mL, CII, announced that it was discontinuing sale and distribution of its product after the current inventory was depleted (Roxanne Laboratories, Inc., 2003).

6

Non-pharmacological control groups in the four non-placebo trials include those assigned to waitlist (Dole, 1969; Yancovitz, 1991), drug-free rehabilitation (Gunne and Gronbladh, 1981), or methadone detoxification (Vanichseni, 1991).

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

placebo-controlled (Newman and Whitehill, 1979; Strain et al., 1993). The overall methodological quality of the studies was good. The procedures for ensuring that researchers and participants remained unaware of the randomization assignments were inadequate in one study (Dole et al., 1969), not adequately described in four studies (Gunne and Gronbladh, 1981; Newman and Whitehill, 1979; Strain et al, 1993; Vanichseni et al., 1991), and good in another (Yancovitz, 1991). Sample sizes were sometimes small, with two studies enrolling only 32 and 34 participants (Dole et al., 1969; Gunne and Gronbladh, 1981). Sample sizes for the four remaining studies ranged from 100 to 301 patients. Dosage was considered adequate in all studies.

The Cochrane meta-analysis examined the impact of treatment on treatment retention, opioid drug use as measured by self-reports and urine analyses, criminal activity, and mortality. The meta-analysis showed that MMT was more effective than placebo and non-pharmacological treatments in retaining patients in treatment (3 RCTs; relative risk [RR]=3.05; 95% confidence interval [CI]: 1.75–5.35), and in reducing heroin use (3 RCTs; RR=0.32; 95% CI: 0.23–0.44). The review found a positive—although not statistically significant—effect on reducing criminal activity (3 RCTs’ RR=0.39; 95% CI: 0.12–1.25) and mortality (3 studies, 435 patients; RR=0.49; 95% CI: 0.06–4.23).

One RCT of MMT (Schwartz et al., 2006), published since the Cochrane review, supported these findings. The study randomly assigned a total of 319 participants on a 3:2 basis to interim methadone maintenance (with an individually determined dose and no regularly scheduled drug counseling) for 120 days (n=199), or a waiting list for community-based methadone treatment (n=120). Some 76 percent of those assigned to the interim methadone maintenance treatment entered comprehensive methadone treatment within 4 months, compared with some 21 percent (p<0.001) assigned to the waiting list. Interim methadone participants also reported significantly fewer days of heroin use (p<0.001), and had significantly fewer heroin-positive urine tests (<0.001). Self-reported crime was also significantly lower in the treatment. The finding that MMT reduces heroin use is consistent with the findings of the Cochrane review.

While RCTs have shown that MMT reduces heroin use and improves treatment retention, findings also suggest a positive effect of MMT on criminal behavior. As noted, the 2003 Cochrane review (Mattick et al., 2003a) found a positive but non-significant association between MMT and reductions in crime. Two quasi-experimental studies examining the effects of MMT program closures in California (Anglin et al., 1989; McGlothin and Anglin, 1981) found that MMT patients who were unable or unwilling to transfer to a private MMT program after a publicly funded MMT program was closed had higher rates of illicit drug use, arrest, and incarcera-

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

tion than patients in other locations who continued to receive MMT. Another study that followed a sample of opioid-dependent men enrolled in MMT found—when comparing pre- and post-admission periods—that retention in methadone treatment had a small but significant effect on criminal activity (Rothbard et al., 1999). Although these studies suggest that MMT has a positive impact on reducing crime, the results must be interpreted with caution because of the strong possibility of selection bias. That is, patients who enrolled in treatment might have reduced their criminal activity in any event, while patients who did not enroll might not have reduced their criminal activity even with treatment.

A number of studies have examined the impact of methadone treatment on mortality. As noted, the Cochrane review (Mattick et al., 2003a) on effectiveness of methadone maintenance found a trend suggesting that methadone had a protective effect on mortality, but it was not significant. Other non-experimental studies point to a reduction in mortality rates among people receiving opioid agonist treatment compared to out-of-treatment IDUs. For example, in a cohort study by Caplehorn et al. (1994), individuals who had left methadone maintenance treatment were three times more likely to die than those who were in treatment. Three studies by Fugelstad and colleagues (1995, 1997, 1998) found nearly all deaths of patients on methadone maintenance were due to disease already present prior to their entry to treatment (e.g., HIV), whereas the majority of heroin addicts out of treatment died as a result of overdose or violence. The significant limitation of non-experimental studies such as these is that self-selection bias could contribute to the findings of decreased mortality among people in treatment.

Buprenorphine

Another Cochrane review (Mattick et al., 2003b) examined the effectiveness of buprenorphine maintenance therapy vs. placebo or methadone maintenance therapy in retaining patients in treatment and reducing illicit drug use. The review considered 13 RCTs that met the inclusion criteria. All but one of the studies were double-blind, but only two were placebo-controlled (Johnson et al., 1995; Ling et al., 1998); most of the evidence came from comparing buprenorphine and methadone at varying dosage levels. The reviewers found that the methodological quality of the studies was high, except that 11 inadequately described how they concealed the allocation of treatment.

The authors found that high-dose buprenorphine maintenance was more efficacious than placebo and low-dose methadone in retaining individuals in treatment and reducing heroin use. However, high-dose buprenorphine had no advantage over high-dose methadone in retaining

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

patients, and was less efficacious than high-dose methadone in reducing heroin use.

Three RCTs of buprenorphine have been published since the 2003 Cochrane review, and their findings are consistent with that review. The first trial (Fudala et al., 2003) tested the efficacy and safety of buprenorphine and combined buprenorphine-naloxone7 treatment in a U.S. office-based setting. In this multicenter, randomized, placebo-controlled trial, 323 opioid-dependent individuals received one of three treatments: (1) sublingual buprenorphine (16 milligrams) with naloxone (4 milligrams) (n=109); buprenorphine alone (16 milligrams) (n=105); or daily placebo for 4 weeks (n=109). The primary outcome measures were opioid-negative urine samples and patients’ self-reported craving for opiates.

The researchers ended the placebo arm of the trial early because both the mono-buprenorphine tablet and the combination buprenorphine-naloxone tablet were more efficacious than placebo. The active treatment groups had higher percentages of opiate-free urine samples (17.8 percent for combined treatment and 20.7 percent for buprenorphine treatment) than the placebo group (5.8 percent; p<0.0001 for both comparisons). The active treatment groups also reported less craving for opiates than the placebo group. The later phase of the study showed that treatment was safe and well tolerated.

The second study was a randomized, double-blind, placebo-controlled trial in Norway (Krook et al., 2002). This 12-week study compared interim buprenorphine maintenance treatment versus placebo in patients on a waitlist for medication-assisted rehabilitation. Participants did not receive any psychosocial treatment as part of the study. Of 106 participants, 55 were randomized to receive a daily dose of 16 milligrams of buprenorphine, and 51 to placebo. Outcome measures included treatment retention, treatment compliance, self-reported drug abuse, well-being, and mental health status.

The average number of days in treatment was higher for the buprenorphine group (42 days) than the placebo group (14 days; p<0.0001). However, the attrition rate was significant for both groups, with 16 participants remaining in the buprenorphine group and 1 in the placebo group after 12 weeks. The authors attribute the retention problem to the lack of psychosocial support. The buprenorphine group also showed a larger drop in self-reported opioid use (p<0.001) and other drug and alcohol use (p<0.01), and a stronger increase in reported well-being (p<0.01) and life

7

Naloxone is an opioid antagonist similar to naltrexone. Naloxone was included to reduce or prevent potential diversion or misuse of buprenorphine by injection.

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

satisfaction (p<0.05). Although these findings are consistent with those of other trials, this trial did not use urine toxicology screening to verify self-reported drug use.

The third study (Kakko et al., 2003) was a randomized, placebo-controlled trial conducted in Sweden to assess the 1-year efficacy of buprenorphine combined with psychosocial therapy in treating heroin dependence. Subjects included 40 individuals who had been dependent on heroin for at least 1 year (all but one injected heroin), but who were not eligible for methadone maintenance treatment. (In Sweden at the time of the trial, individuals were eligible only after 4 years of multiple daily heroin use and more than three unsuccessful attempts at drug-free treatment.) Participants were randomly assigned (1:1) to daily buprenorphine (16 milligrams per day for 12 months, with supervised administration for 6 months and possible take-home doses after that), or to a tapered buprenorphine regimen for 6 days followed by placebo. As part of a relapse-prevention program, all patients received cognitive-behavioral group therapy and weekly individual counseling. Participants submitted urine samples for testing for illicit opiates, stimulants, cannabinoids, and benzodiazepines. The primary outcome measure was retention in treatment for 1 year.

Results from Kakko et al. (2003) showed 75 percent treatment retention in the buprenorphine treatment group and 0 percent in the placebo group (p=0.0001; risk ratio: 58.7; 95% CI: 7.4–467.4). The authors attribute the high attrition rate in part to criteria that required involuntary dismissal from treatment for anyone who continued using illicit drugs. All 20 patients in the placebo group had urine tests that were positive for illicit drug use, and none remained in treatment beyond 2 months. In the buprenorphine group, four were involuntarily discharged for positive urine toxicology tests, and one voluntarily dropped out of treatment. The authors also note that withdrawal symptoms and perceived lack of suppression of craving among participants in the placebo arm could have contributed to illicit drug use and dropout. Urine samples in the buprenorphine group were 74.8 percent (standard deviation 59.6 percent) negative, on average, for substances analyzed. Mortality was substantially higher in the control group: four people (20 percent) died in the control group, and none in the buprenorphine group. The authors conclude that buprenorphine combined with psychosocial treatment is highly efficacious and safe.


Based on this evidence, the Committee concludes:

Conclusion 2-1: Strong and consistent evidence from well-designed, randomized, controlled trials (some double-blind, placebo-controlled) shows that opioid agonist maintenance treatment—including methadone and buprenorphine—is more effec-

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

tive than placebo and non-pharmacological treatment in reducing illicit opioid use and increasing retention in drug-abuse treatment for opioid-dependent patients. When available and accessible, opioid agonist maintenance treatment attracts and retains in treatment a large proportion of opioid dependent patients and thus can have a substantial public health benefit in the population.


Conclusion 2-2: Moderate evidence from randomized controlled trials and quasi-experimental studies suggest that opioid agonist maintenance therapy is associated with reductions in criminal behavior. Modest evidence from studies suggest that agonist maintenance therapy lowers mortality risk for those who remain in treatment, but the possibility of self-selection bias cannot be excluded.

Effects on Non-Opioid Drug Use

Concomitant abuse of other drugs is a common problem for opioid-dependent individuals, including patients on methadone and buprenorphine maintenance treatment. Co-occurring drug use among opioid-dependent people can increase rates of morbidity and mortality and undermine the effectiveness of opioid addiction treatment (Backmund et al., 2003; Leri et al., 2003).

Cocaine use, in particular, is prevalent among opioid-dependent people. The estimated prevalence of cocaine use among heroin-dependent people not in treatment ranges from 30 to 80 percent (Haisin et al., 1988; Schottenfeld et al., 1993; Schutz et al., 1994; Frank and Galea, 1996; Grella et al., 1995, 1997 as cited in Leri et al., 2003). Studies have also found high rates of chronic or intermittent cocaine use among patients enrolled in methadone programs (Kosten et al., 1987, 1988; Magura et al., 1998; cited in Leri et al., 2003). The effects of co-occurring cocaine use are particularly serious (Leri et al., 2003). Cocaine is most often injected in this population, and because of its short half life, can be injected more often, producing more opportunities for syringe sharing and a higher risk of HIV infection and other infectious diseases (Leri et al., 2003). Furthermore, opioid addicts who use cocaine are also more likely to have poor treatment outcomes, such as high dropout rates, involuntary dismissal from treatment, and high rates of relapse (Leri et al., 2003).

Concomitant use of alcohol, benzodiazepines, barbiturate, cannabis, and other drugs among opioid-dependent populations is also prevalent (Fairbank et al., 1993; Darke et al., 1995; Rooney et al., 1999; Hser et al., 2001; Backmund et al., 2003). Use of these drugs is also concerning. For instance, consumption of opioids and psychotropic substances with

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

respirant-depressive effects, such as alcohol, benzodiazepines, barbiturates, can lead to overdoses that are sometimes fatal (Backmund et al., 2003).

Because opioid agonist treatment is not pharmacologically specific to non-opioid drugs, we would not expect to see an impact on adjunctive drug use without additional intervention. While some studies have examined whether opioid agonist maintenance therapy is associated with changes in patterns of stimulant or other drug use, many of these studies had limitations that made it difficult to interpret or generalize their results, such as cross-sectional design, short time period, reliance on self-reported data, small sample size, or a single study site (Magura et al., 1998). No recent reviews have examined whether opioid agonist treatment is associated with changes in patterns of stimulants or other drug use.

Nevertheless, understanding patterns of concomitant drug use among opioid-dependent people—including those enrolled in opioid agonist treatment—is important to understanding HIV-related risks and in designing appropriate interventions for these populations. As discussed later in this chapter, the addition of certain behavioral interventions to opioid agonist maintenance therapy has been effective in reducing overall drug use for patients who are co-dependent on stimulants and opioids.

Effects on HIV Risk Behavior and Seroconversion

Opioid agonist treatment may reduce the risk of HIV infection in several ways. By reducing the use of opioids, such treatment may also reduce how often individuals inject, and also how often they share injecting equipment. These impacts depend partly on whether individuals are using opioids only or also using other drugs that may be injected, such as cocaine and amphetamine-type stimulants. Agonist treatment may also reduce the need to engage in high-risk behavior, such as exchanging sex for money or drugs. Such treatment may further connect users of illicit drugs with health and social services, and make them more receptive to prevention messages (Gowing et al., 2004).

A recent Cochrane review (Gowing et al., 2004; summary in Gowing et al., 2005) examined the effects of opioid agonist treatments on drug-related and sex-related HIV risk behavior and HIV seroconversion. The authors identified 28 studies of methadone treatment that met the criteria for inclusion: these studies specifically examined HIV risk behavior or incidence in relation to opioid agonist treatment, and the study authors described the treatment regimen adequately.

Of the 28 studies, 2 were randomized controlled studies (Dolan et al., 2003; Sees et al. 2000), 3 were prospective cohorts (Kwiatkowski and Booth, 2001; Maddux and Desmond, 1997; Metzger et al., 1993), and 2 were case controls (Moss et al., 1994; Serpellini and Carrieri, 1994). The

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

remaining studies were classified as “other descriptive studies.”8 Because the methodologies of the studies varied, the authors limited their analysis to a descriptive review that compared outcomes of the studies. In its own review, the Committee gave the most weight to evidence from the 7 studies with the strongest study designs, including controlled clinical trials, prospective cohorts, and case-control studies.

Drug-Related HIV Risk Behavior

Frequency of injecting: Six of the 28 studies provided the proportion of participants reporting injecting drug use before and after methadone treatment.9 Eight studies offered data on the reported frequency of injection at baseline and follow-up,10 and 2 studies11 examined both the proportion and frequency of injection. One study was an RCT (Dolan et al., 2003), while the others were classified as descriptive. The studies varied in design, follow-up period, and method of reporting the frequency of injecting (such as frequency score, actual number of injections, and days of injecting use). However, they all showed statistically significant decrease in injecting behavior from baseline to follow-up—periods that ranged from 3 to 12 months (Gowing et al., 2004, 2005).

In the one RCT (Dolan et al., 2003), investigators studied whether MMT reduced heroin use and syringe sharing among opiate-dependent individuals in an Australian prison system from 1997 to 1998. Of 593 eligible prisoners seeking drug treatment, 382 were randomly assigned to MMT (30 milligrams per day initially, increased up to 60 milligrams) (n=191), or a waitlist control group (n=191). Researchers used toxicology tests of hair samples and self-reports to measure heroin use, and self-reports to measure drugs used and the frequency of injection and syringe sharing. Study subjects were interviewed at baseline and about 4 months later. At follow-up, 129 (68 percent) of the MMT group and 124 (65 percent) of the control group who had been in continuous custody were reinterviewed. Participants in the MMT group had significantly lower levels (p<0.001) of

8

If a controlled clinical trial collected data on HIV seroprevalence and risk behavior for secondary analysis (such as during a study primarily designed to test the efficacy of methadone versus buprenorphine on drug use), the Cochrane reviewers regarded these data as being derived from a descriptive study (Gowing et al., 2004).

9

RCT (Dolan et al., 2003); descriptive studies (Camacho et al., 1996; Chatham et al., 1999; Gossop et al., 2000; King et al., 2000; Magura et al., 1991).

10

RCT (Dolan et al., 2003); descriptive studies (Batki et al., 1989; Brooner et al., 1998; Camacho et al., 1996; Chatham et al., 1999; Kwiatkowski and Booth, 2001; Simpson et al., 1995; Strang et al., 2000).

11

Descriptive studies (Camacho et al., 1996; Chatham et al., 1999).

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

self-reported drug injection than controls in each of the three months before the follow-up interview. The treatment and control groups did not show significant differences in heroin use as measured by nanograms in hair, but the hair tests are not sensitive to differences in frequency of heroin use, so the lack of significant differences does not necessarily contradict the validity of the findings based on self-report.


Sharing of injecting equipment: Seven studies examined the proportion of participants who reported sharing injecting equipment before and after a period of MMT. Six of seven studies12 found a significant reduction in sharing between baseline and follow-up periods. The seventh study (King et al., 2000) found a non-significant reduction in reported syringe sharing (risk ratio 0.54; 95% CI: 0.23–1.27) (Gowing et al., 2004, 2005).

Four studies (Dolan et al., 2003; Metzger et al., 1993; Stark et al., 1996; Thiede et al., 2000) also provided data on sharing of injecting equipment among those who received MMT compared with those who received no methadone or only limited doses. In three studies (Dolan et al., 2003; Metzger et al., 1993; Stark et al., 1996), those receiving MMT were significantly less likely to report sharing injecting equipment. In the study with the strongest design, the RCT by Dolan et al. (2003), treated subjects had lower reported levels of syringe sharing at follow-up than controls (20 percent vs. 54 percent, p<0.001) (Gowing et al., 2004, 2005).


Drug-related risk scores: Four studies provided data on drug-related HIV risk scores before and after MMT.13 Three of the four studies (Abbott et al., 1998; Avants et al., 1998; Chatham et al., 1999) found significant decreases in drug-related HIV risk behavior before and after MMT. The fourth study (Sees et al., 2000), an RCT, found a non-significant reduction in mean risk scores between intake and the 6-month follow-up for both the MMT and 180-day methadone detoxification groups (Gowing et al., 2004, 2005).

A final study (Baker et al., 1995) compared drug risk scores for cohorts of IDUs who currently, previously, or never received MMT. The study found a significant reduction in risk-related scores for the group receiving MMT, compared with the latter two groups combined (the proxy for not in methadone treatment) (Gowing et al., 2004, 2005).

12

RCT (Dolan et al., 2003); descriptive studies (Camacho et al., 1996; Chatham et al., 1999; Gossop et al., 2000; King et al., 2000; Grella et al., 1996; Margolin et al., 2003).

13

These studies used rating scales such as the Risk Assessment Battery and the HIV Risk Taking Behavior Scale to derive both drug-related and sex-related HIV risk scores and an overall HIV risk score (Gowing et al., 2004, 2005). This section focuses on drug scores.

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

Based on this evidence, the Committee concludes:

Conclusion 2-3: Moderate to strong evidence from one RCT and a number of observational studies shows that patients receiving methadone maintenance treatment report reductions in several drug-related HIV risk behaviors, including frequency of injecting and sharing of injecting equipment. These patients also had lower summary scores of drug-related risk behavior compared with pretreatment levels.

Sex-Related HIV Risk Behavior

Because opioid agonist maintenance therapy is not designed to reduce sexual risk behavior, one would not expect to see an impact on such behavior use without additional intervention. However, the Cochrane review identified a number of observational studies that have examined the impact of MMT on sex-related risk behavior, including multiple sex partners, exchange of sex for drugs or money, and unprotected sex (Gowing et al., 2004, 2005).


Multiple sex partners and commercial sex: Four studies—classified as descriptive by Cochrane—provided data on the proportion of participants reporting multiple sex partners or exchanges of sex for drugs or money. In three of these studies (Camacho et al., 1996; Chatham et al., 1999; Grella et al., 1996), participants reported significantly fewer multiple partners or exchanges of sex for drugs or money after MMT than before treatment. In King et al. (2000), relatively few participants reported such behavior before or after MMT (Gowing et al., 2004, 2005).

Two studies reported on sex-related risk behavior among cohorts of IDUs either receiving or not receiving methadone treatment. In a prospective cohort study by Metzger et al. (1993), significantly more participants in the out-of-treatment cohort reported commercial transactions for sex in the 6 months before baseline than participants in the methadone treatment cohort (46 percent vs. 28 percent; p<0.01). The out-of-treatment group also reported a higher average number of sex partners (4.6 versus 2.3; p<0.01) during the same period.

In a cross-sectional study by Meandzija et al. (1994), participants in the methadone treatment cohort reported fewer sex partners in the past 30 days than out-of-treatment injection drug users, although the result was not statistically significant. The in-treatment cohort also reported a significantly lower frequency of exchanging sex for money or drugs during the past 30 days, compared with the out-of-treatment cohort (Meandzija 1994; Gowing et al., 2004, 2005). The Cochrane review (Gowing et al., 2004)

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

identified a third cohort study (Britton, 1994) that found differences in the number of sex partners between cohorts of drug users continuing in or stopping methadone. However, the review gave little weight to the findings because of the significant differences between the groups at baseline (Gowing et al., 2004, 2005).


Unprotected sex: The measure for assessing exposure to unprotected sex varied substantially across studies included in the Cochrane review. Six of the studies14 defined such exposure as the use of condoms in half or fewer sexual encounters. Four of these studies (Camacho et al., 1996; Chatham et al., 1999; Gossop et al., 2000; Margolin et al., 2003) found statistically significant reported reductions in unprotected sex, while two did not. In Grella et al. (1996), fewer participants reported unprotected sex at follow-up compared with baseline, but the finding was not significant. In King et al. (2000), the number of participants reporting unprotected sex actually rose slightly after treatment, but the finding was not significant.

Three studies compared condom use among groups of IDUs in or out of methadone treatment. One cohort study (Metzger et al., 1993) and one cross-sectional survey (Meandzija et al., 1994) found no significant differences in reported condom use between in-treatment and out-of-treatment groups. A third cohort study (Stark et al., 1996) found non-significant drops in reported condom use in the methadone treatment cohort compared with the out-of-treatment cohort (Gowing et al., 2004, 2005).


Sex-related risk: Four studies reported on sex-related risk scores. Two (Abbott et al., 1998; Avants et al., 1999) reported a significant reduction in sex-related risk from baseline to 6-month follow-up. A randomized controlled trial (Sees et al., 2000) found a reduction in sex-related scores, but it was not significant. A final study (Baker et al., 1995) found no difference in sex-related risk scores for IDUs in methadone treatment compared with IDUs who were previously in treatment or had no prior history of MMT (Gowing et al., 2004, 2005).

Based on this evidence, the Committee concludes:

Conclusion 2-4: Because opioid agonist maintenance therapy is not designed to reduce sex-related risk behavior, one would not expect to see a substantial impact on such behavior without additional intervention. Indeed, evidence from observational studies is

14

Descriptive studies: Camacho et al. (1996); Chatham et al. (1999); Gossop et al. (2000); Margolin et al. (2003); Grella et al. (1996); King et al. (2000).

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

weak and inconclusive on whether opioid agonist therapy alone is associated with reductions in high-risk sexual behavior. Some studies suggest that MMT is associated with small reductions—compared with pre-treatment baseline measures—in the number of sexual partners and exchanges of sex for money or drugs, but that it has virtually no effect on reported rates of unprotected sex.

HIV Seroconversion

Four studies in the 2004 Cochrane review specifically examined the impact of MMT on HIV seroconversion (Gowing et al., 2004, 2005). In a prospective cohort study, Metzger et al. (1993) followed 152 people in methadone treatment and 103 out-of-treatment opiate users in Philadelphia for 18 months. At baseline, the HIV seroprevalence rate was 10 percent for the in-treatment group and 16 percent for the out-of-treatment group. A follow-up study of HIV-negative participants over the next 18 months found a six-fold difference in seroconversion rates among those in treatment (3.5 percent) and out of treatment (22 percent). Of the participants, 46 percent (n=85) were in treatment during the entire 18-month period, 24 percent (n=45) attended treatment intermittently, and 30 percent (n=55) were not in treatment at any point. The odds of seroconversion were 7.63 among untreated subjects (95% CI: 1.99–29.27; p<0.01) and 1.08 (not significant) among intermittent-treatment subjects compared with subjects in continuous MMT. Untreated subjects were thus seven times more likely to seroconvert during the 18-month period than individuals who remained in treatment. These findings persisted in analysis controlling for confounders, although the possibility of self-selection bias exists.

Moss et al. (1994) followed a cohort of IDUs entering MMT or detoxification in San Francisco from 1985 to 1990. In a subsample of 681 who were HIV-negative at first visit and seen at least twice, 22 seroconverted. Using a case-control design and stratifying the sample by time spent in methadone treatment, the authors found that 11 of 145 (7.6 percent) who spent less than 12 months in treatment seroconverted, compared with 11 of 536 (2.1 percent) who spent more than 12 months in treatment (adjusted hazard ratio 4.0; p=0.002). A history of 1 or more years in methadone maintenance (per lifetime) was therefore a highly protective factor against HIV seroconversion. This effect persisted, in both men and women, after adjustment for race and other confounding factors. Nonetheless, the possibility of selection bias could not be ruled out.

Serpellini and Carrieri (1994) conducted a nested case-control study of seroconverters (cases) who were part of a cohort of 952 HIV-negative IDUs (controls) followed from 1985 to 1991, to assess the impact of MMT on HIV infection. The study included 40 cases and 40 controls. Controls were

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

matched with cases on sex, age, duration of drug use, and follow-up time. In multivariate analyses, lower daily dose and more time out of methadone treatment were associated with higher HIV seroconversion. Time spent in methadone treatment was the major determinant of remaining HIV-free; the model showed that the risk of becoming HIV infected increased 1.5 times for every 3 months (of the last 12) spent out of methadone treatment. The authors similarly found a significant inverse relationship between average daily methadone dose and HIV seroconversion.

Williams et al. (1992) conducted a follow-up study of a cohort of MMT clients in New Haven with a history of injecting drug use. The study followed 98 IDUs who were HIV-seronegative at baseline and who completed at least one follow-up visit for a mean of 39 months. Nine participants seroconverted during the follow-up period, and 89 remained seronegative. Stratified by time in treatment, subjects who remained on methadone treatment without interruption during the follow-up period were less likely to seroconvert than those in the interrupted-treatment group. One participant of the 56 in the continuous-treatment group seroconverted, compared with 8 of the 42 in the interrupted-treatment group (odds ratio [OR]=12.9; 95% CI: 1.6–584, p=0.0045). Because the follow-up period varied by group (averaging 29 months in the continuous-treatment group versus 53 months in the interrupted-treatment group), the seroconversion rate per person-year was computed for each group. The HIV-1 seroconversion rate was 0.7 per 100 person-years (95% CI: 0.1–5.3) for the continuous-treatment group, and 4.3 per 100 person-years (95% CI: 2.2–8.6) for the interrupted-treatment group. The difference between seroconversion rates in the two groups was not significant (Z=1.65; p=.10; two-sided). Continuous methadone treatment had a non-significant association with lower HIV seroconversion. However, the small sample size and the risk of selection bias arising from loss to follow-up are important limitations of this analysis.

Based on this evidence, the Committee concludes:

Conclusion 2-5: Modest evidence from prospective cohort and case-control studies shows that continuous opioid agonist maintenance treatment is associated with protection against HIV sero-conversion. This association persists after controlling for many confounders. These studies also show that the risk of HIV sero-conversion is inversely related to the length of time in treatment. However, the possibility of bias in these findings from self-selection cannot be ruled out: that is, patients who resist treatment or engage in risky behaviors may leave treatment, while patients with fewer HIV risk behaviors may stay in treatment longer.

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

Conclusion 2-6: Evidence regarding the effects of agonist maintenance therapy on HIV-related risk behavior and HIV seroconversion is based on studies of methadone conducted in developed countries. Other studies (reviewed in the previous section) found that buprenorphine has comparable efficacy in reducing dependence on illicit opioids. Nothing in the literature contradicts the logic that buprenorphine would exert an effect on HIV risk behavior and incidence comparable to that of methadone treatment. Nor does the literature suggest that the effectiveness of opioid agonist maintenance treatment would be diminished in developing countries.

Factors Affecting Outcomes of Opioid Agonist Treatment

As noted, studies have shown that opioid agonist treatment reduces illicit opioid use, improves retention in treatment, and reduces drug-related HIV risk behavior and incidence. Three major clinical factors that increase the likelihood of these positive outcomes are appropriate length of treatment, adequate dosage, and provision of psychosocial treatments along with maintenance medications.

Length of Treatment

The Committee identified four randomized controlled trials that compared methadone maintenance treatment with methadone-assisted detoxification. In all cases, maintenance treatment was found to be superior to detoxification in terms of treatment retention and heroin use. In the first RCT (Sees et al., 2000), investigators compared outcomes for opiate-dependent patients on MMT versus long-term (180-day) methadone-assisted detoxification. Results showed that patients in the MMT arm had improved treatment retention and lower heroin use than the detoxification group. Dropout rates were significantly higher in the detoxification arm than in the MMT arm. Drug-related HIV risk behavior, but not sex-related risk behavior, also declined more in the MMT group.

A second RCT conducted in Thailand found that patients assigned to MMT had greater likelihood of completing treatment and were less likely to use heroin than those assigned to a short-term (45-day) methadone detoxification arm (Vanichseni et al., 1991). A third RCT by Newman and Whitehill (1979) conducted in Hong Kong found that the MMT group had greater treatment retention than the control group, which was detoxified (dose of methadone was decreased by 1 milligram per day) and then maintained on placebo. At the end of 32 weeks, only 10 percent of the controls were still in treatment, compared with 76 percent of the MMT

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

group. At the end of 3 years, only 1 of the original 50 patients assigned to detoxification/placebo was still in treatment, while 56 percent of MMT patients remained in treatment.

Finally, Strain et al. (1993) found that patients on active maintenance therapy had higher treatment retention rates than those who entered a 35-day detoxification period and then remained on placebo. Illicit opiate use was also lower among patients on 50 milligrams of methadone per day, compared with those receiving 20 or 0 milligrams per day. In addition, as noted above, quasi-experimental studies examining the effects of program closures in California found higher rates of illicit drug use, arrest, and incarceration among those whose MMT was terminated (even after prolonged MMT) than among comparison samples in other locations who continued to receive MMT during the same period (Anglin et al., 1989; McGlothin and Anglin, 1981).

Based on this evidence, the Committee concludes:

Conclusion 2-7: Strong evidence from several large, randomized clinical trials shows that continuous agonist maintenance therapy is associated with longer treatment retention—and reductions in illicit opioid use and relapse to opioid dependence—than short-term use of these agents. Furthermore, modest evidence from quasi-experimental studies also suggests that discontinuation of agonist maintenance therapy is associated with higher rates of readdiction and criminal behavior. Agonist maintenance therapies are effective while they are provided, and no evidence suggests a benefit to early termination. Thus, reasonable clinical guidance is to continue such therapies as long as they are associated with positive effects.

Dosage

Regulations and clinical practice standards for long-term opioid maintenance therapy vary widely (Faggiano et al., 2003). However, strong evidence from a variety of sources shows that methadone maintenance is a dose-dependent treatment; that is higher doses of opioid agonist therapies are more efficacious than moderate and lower doses in managing opioid dependence.

In a recent Cochrane review (Faggiano et al., 2003), the authors examined results from 21 studies (10 randomized controlled trials and 11 controlled prospective studies), to compare the effectiveness of MMT at different doses. The results of this review support the conclusion that high dosages of 60–100 milligrams per day of methadone are more effective than low doses (1–39 milligrams per day) and moderate doses (40–59 milligrams per

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

day) in retaining patients in treatment and reducing the use of heroin during treatment. A study by Strain and colleagues (1999) also illustrates that benefits increase with higher doses. An RCT comparing the clinical efficacy of moderate-dose (40–50 milligrams per day) vs. high-dose (80–100 milligrams per day) methadone maintenance found that while both groups decreased their illicit opioid use, the high-dose methadone group had significantly greater decreases.

Although high doses show the greatest benefits, low-dose or “low-threshold” methadone programs have been used in some places, notably in Amsterdam, to encourage more opiate-dependent people to enter treatment. The Amsterdam programs made methadone easily accessible (e.g., through use of mobile vans, absence of waiting lists) and acceptable to users (e.g., by allowing participation regardless of illicit drug use, offering services in a supportive way, and making it easy to enter or leave the program) (van Ameijden et al., 1999). The goal of the program was to stabilize drug users by preventing withdrawal symptoms in the hopes that they will gradually move toward more intensive treatment for drug dependence (Hartgers et al., 1992). The low-threshold programs in Amsterdam succeeded in bringing 60–70 percent of heroin-dependent individuals into methadone treatment (Termorshuizen et al., 2005). One follow-up study of the programs found, however, that low-threshold programs did not provide any protective effect against HIV seroconversion (Hartgers et al., 1992). Length of time participating in the low threshold program was positively correlated with HIV infection; that is, long-term participants had a higher prevalence of HIV infection than short-term or irregular participants (Hartgers et al., 1992). While there are many confounders to this study, the study provides no evidence that the low-dose programs decrease HIV transmission risk.

While fewer studies compare higher and lower doses of buprenorphine, dose-ranging studies show dose-dependent effects of buprenorphine on heroin use in heroin-dependent patients. Animal and human laboratory studies also show dose-dependent effects of buprenorphine on heroin self-administration. Some randomized controlled trials show greater reductions in illicit opioid use associated with higher daily doses of buprenorphine (12–16 milligrams), compared with lower doses (2–4 milligrams) (Ling et al., 1998; Johnson et al., 1995; Schottenfeld et al., 1993, 1997).

The optimal doses for individuals are the joint decision of clinicians and patients. However, clinicians, policymakers, and regulators should consider the strong dose-response effects of opioid agonist therapies when developing guidelines, and avoid setting arbitrary dosage limits.

Based on this evidence, the Committee concludes:

Conclusion 2-8: Strong evidence from randomized, double-blind clinical trials, shows that buprenorphine and methadone mainte-

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

nance treatments have greater efficacy at higher doses. Thus, reasonable clinical guidelines would recommend raising the dose until optimal effects occur, rather than setting arbitrary limits. Studies systematically examining dosing show greater efficacy up to 100 milligrams per day of methadone, and up to 16 milligrams per day of buprenorphine. Doses up to 160 milligrams per day of methadone, and up to 24 milligrams per day of buprenorphine, have been shown to be safe in patients whose dose has been gradually titrated to these levels over a sufficient period of time.

Combined Psychosocial and Agonist Maintenance Treatment for Opiate Dependence

As noted, studies have shown the effectiveness of opioid agonist maintenance therapy in retaining patients in treatment, reducing illicit opiate use, reducing drug-related HIV risk behavior, and protecting against HIV seroconversion. Many developed countries provide MMT in conjunction with some form of psychosocial support, which may also be legally mandated. The Committee reviewed evidence of the effectiveness and added benefit of psychosocial treatments offered with agonist maintenance treatment programs.


Drug use and treatment outcomes: A 2004 Cochrane review (Amato et al., 2004) examined evidence on the effectiveness of psychosocial interventions combined with opioid agonist maintenance treatment, versus opioid agonist maintenance treatment alone. The 12 studies identified for the review covered eight different psychosocial interventions used with agonist maintenance treatment. The authors classified these psychosocial interventions into several categories: behavioral interventions (biofeedback, cognitive behavioral therapy, community reinforcement, and contingency management), psychoanalytic treatments (subliminal stimulation and supportive-expressive therapy), structured counseling, and interpersonal psychotherapy. The review authors concluded that psychosocial interventions added some benefit to opioid agonist maintenance treatment in reducing heroin use, but not in retaining individuals in treatment.

The Committee found the overall evidence in the Cochrane review weak, owing to the poor methodological quality of all but 1 of the 12 studies,15 and the heterogeneity of the interventions and outcomes. Fur-

15

The Cochrane review group classified 10 of the 12 studies as having a moderate risk of bias, and 1 as having a high risk of bias (Amato et al., 2004).

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

thermore, only 1 of the 12 studies addressed the question: Do psychosocial interventions add to the efficacy of opioid agonist maintenance treatment? The remaining 11 studies compared either (1) groups receiving combined psychosocial and agonist maintenance treatment vs. groups receiving psychosocial treatment alone; or (2) groups receiving agonist maintenance treatment with standard drug counseling vs. groups receiving “enhanced” psychosocial services. These study designs did not directly answer the question.

The 1 study (McLellan et al., 1993) of the 12 that was most relevant was an RCT that examined whether the addition of counseling, medical care, and psychosocial services improved the outcomes of opiate-dependent persons enrolled in methadone maintenance treatment. Participants (92 male veterans who were injecting opiate users) were randomly assigned to one of three conditions: (1) minimum methadone services (MMS)—methadone alone (at least 60 milligrams per day) with no other services (n=32); (2) standard methadone services (SMS)—the same dose of methadone plus counseling (n=29); (3) enhanced methadone services (EMS)—the same dose of methadone plus counseling, onsite medical and psychiatric services, employment counseling, and family therapy (n=31).

While MMS was associated with reductions in opiate use, 69 percent of the participants in this group had to be “protectively transferred” to a “treatment-as-usual” condition (which included counseling, thereby approximating the SMS treatment in the trial), because of continued use of opiates or cocaine or the occurrence of several medical or psychiatric emergencies. This result was significantly different from that of the 41 percent of participants in the SMS treatment condition and the 19 percent of participants in EMS who met the criteria for protective transfer. Because patients in SMS were receiving the equivalent of the treatment-as-usual services, and those in EMS were receiving enhanced services, they were not actually transferred.

At the end of the 6-month follow-up period, the 10 individuals who remained in the MMS group showed statistically significant improvement in the drug-use factor score, and the number of days of opiate use, but not on other outcomes. Patients enrolled in the SMS had significantly better outcomes, with significant decreases in both opiate and cocaine use, and some positive but weaker changes in alcohol, legal, family, and psychiatric measures. Finally, EMS patients had the best outcomes, with statistically significant improvement in drug and alcohol use, employment status, illegal activities, family relations, and psychiatric status. Patients assigned to the MMS group who were protectively transferred (n=22) showed significant reductions in cocaine and opiate use after 4 weeks.

When assessing the relative efficacy of the treatments, the investigators excluded individuals in the MMS group who moved to standard treatment

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

as a result of protective transfer (n=22). In this “as-treated” analysis, 30 percent of the remaining 10 MMS patients were abstinent from opiates and cocaine at 24 weeks, compared with 55 and 68 percent in the SMS and EMS groups, respectively. However, the Committee’s “intent-to-treat”16 reanalysis—which reclassifies individuals in the MMS who were protectively transferred as “treatment failures,” and includes them in the overall calculation—shows that the proportion of patients who were abstinent from opiates and cocaine at 24 weeks is actually 9 percent (3/32), versus 55 and 68 percent in the SMS and EMS groups. Based on their analysis, the study authors concluded that counseling improved treatment, and that the addition of other onsite psychosocial services was even more beneficial. The Committee’s intent-to-treat reanalysis suggests that the additional benefit of psychosocial services to agonist maintenance treatment is even greater than reported in the original study.

Because virtually all methadone maintenance programs in the United States and other developed countries provide at least some psychosocial intervention (usually drug counseling) in conjunction with agonist treatment, there has been little or no opportunity to further evaluate this issue in these countries. However, developing countries with plans to implement opioid agonist treatment programs can evaluate the effectiveness of adding psychosocial interventions. Furthermore, some developed countries do not require counseling along with buprenorphine maintenance treatment that is provided in office-based settings. Thus investigators in the developed countries may also be able to evaluate these issues. Understanding whether psychosocial interventions in general—and which psychosocial interventions and for which patients in particular—are most effective when combined with agonist maintenance therapy is critical, particularly in countries with constraints on resources and skilled labor.

Based on this evidence, the Committee concludes:

Conclusion 2-9: Most studies have examined the effectiveness of opioid agonist treatment combined with psychosocial treatment, partly because legal mandates in developed countries often require counseling as an integral part of such therapy. As a result,

16

The intention-to-treat principle (Hill, 1961) requires that data from all study participants be used in the analysis, regardless of whether they received the assigned treatment or adhered to the protocol (i.e., complied with treatment). The advantage of intent-to-treat analyses is that it provides an unbiased information on the effects of the treatment, rather than biased information resulting from analyses only on a compliant subsample. Although intent to treat analyses are the gold standard in reporting results of RCTs, they are rarely done because of the difficulty in following up on individuals who drop out of treatment early or violate the protocol (Nich and Carroll, 2002).

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

the additional benefit of adding psychosocial programs to agonist maintenance treatment for opioid-dependent individuals has not been well-studied. Modest evidence from one randomized controlled trial showed that drug counseling plus agonist maintenance treatment is superior to agonist maintenance treatment alone with respect to opiate-dependence outcomes, and that additional onsite psychosocial services further improve outcomes, but more research is needed.

HIV-related outcomes: The Committee identified some studies that examined the effect of psychosocial interventions among patients enrolled in opioid agonist treatment on HIV risk behavior. Four studies included in a meta-analysis (Prendergast et al., 2001), which evaluated the efficacy of combining psychosocial interventions with drug abuse treatment to reduce risk of HIV infection, provided inconclusive results (Courtnage, 1991; Harris et al., 1998; Schilling et al., 1991; Sorensen et al., 1994).

Avants and colleagues (2004) conducted an RCT of the efficacy of a 12-session harm reduction group (HRG) intervention for IDUs that focused on reducing both sex and drug-related HIV risks. Two hundred and twenty patients were randomized to receive either the HRG or a standard care, which included 2 hours of counseling per month and a single risk reduction session. The study found that during treatment, HRG participants were more likely to be abstinent from cocaine and had fewer reports of high-risk sexual behavior. After treatment, HRG patients scored higher on a knowledge test about sex-related risks, and reported higher self-efficacy17 in high-risk sexual situations. Patients in both groups reported lower injecting drug use and needle sharing.

Baker and colleagues (1993) conducted a randomized trial of a six-session relapse prevention program vs. a brief intervention (one-session motivational interview and self-help booklet) and a control condition among 95 IDUs enrolled in a methadone program. The investigators found that the relapse prevention program was slightly more effective in reducing reported needle sharing during relapse periods. There were no differences between the brief intervention and control groups.

Another study evaluated a voluntary AIDS prevention program for patients attending three methadone maintenance clinics in New York City (Magura et al., 1991). The program included AIDS education seminars,

17

“Perceived self-efficacy is defined as people’s beliefs about their capabilities to produce designated levels of performance that exercise influence over events that affect their lives. Self-efficacy beliefs determine how people feel, think, motivate themselves and behave” (Bandura, 1994).

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

peer support groups, and HIV counseling and testing. Patients at clinic 1 received all three components, while patients at clinic 2 were not offered HIV testing, and patients at clinic 3 (control) had no special interventions. At the 2-month follow-up, participation in the AIDS education component was associated with greater knowledge of HIV risks and improved reported attitudes toward the use of condoms. Participation in the peer group was associated with improved reported attitudes toward condom use and a reported increase in the use of condoms. Learning that one was HIV-negative was associated with reduced injection-related risks and improved reported self-efficacy. However, the potential for self-selection bias and the low rates of participation (25 percent attended AIDS education, and a lower percentage attended peer groups and was tested) limit the usefulness of the results.

Overall, these studies suggest that psychosocial interventions with patients on methadone help reduce HIV risk behavior, but methodological limitations make the results difficult to interpret.

Based on this evidence, the Committee concludes:

Conclusion 2-10: Few studies have specifically examined the impact of adjunctive psychosocial interventions on HIV risk behavior among patients on opioid agonist maintenance therapy. Weak evidence from several studies suggest that some psychosocial interventions for patients enrolled in such therapy can be effective in reducing sexual and drug-related HIV risk behavior, but more research is needed.

Unintended Consequences of Opioid Agonist Maintenance Therapy

Despite the many benefits of opioid agonist treatments, the medications used for maintenance treatment can be abused. Thus, weighing the risks of expanding access to treatment—notably, the potential for greater misuse and diversion into illicit markets—against the benefits is important. Methadone diversion is associated with a risk of methadone overdose if the methadone is used by individuals who are not tolerant of the dose. Methadone overdose can also occur if methadone doses are too high or increased too rapidly at the start of treatment (Schottenfeld, 2004). Because buprenorphine is a partial agonist, the risk of overdose is considerably lower, but buprenorphine overdose deaths have been reported, particularly when buprenorphine is used along with benzodiazepines (Kintz, 2001; Reynaud et al., 1998).

Although diverted methadone or buprenorphine may be used in a quasi-therapeutic manner to prevent or treat withdrawal symptoms, both medications may also be injected, and thus contribute to the risks of HIV transmis-

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

sion associated with injecting drug use. Injection of dissolved buprenorphine tablets has been associated with serious adverse effects, including abscesses and optic neuritis (Auriacombe et al., 2004), acute hepatitis among hepatitis C-infected individuals (Berson et al., 2001), and fatalities when combined with benzodiazepines (Kintz, 2001). Arterial ischemia has been reported on rare occasions when buprenorphine is accidentally injected into an artery (Gouny et al., 1999). Injection of methadone can also lead to serious problems and death (Lintzeris et al., 1999; Heinemann et al., 2000; Hopwood et al., 2003).

A number of studies have examined methadone diversion and abuse, particularly in the United States, Europe, and Australia, where methadone has been used for some time. Two recent studies in the United States and in Australia found that large increases in physician prescriptions of methadone tablets for pain management were followed by increased reports of methadone diversion and abuse. The predominant use of methadone tablets in diversion and abuse cases in both areas suggests that methadone tablets were being diverted from the analgesic market rather than from patients attending methadone clinics, with the former providing methadone in syrup or wafer form (Cicero and Inciardi, 2005; Williamson et al., 1997). Germany also experienced an increase in methadone-related overdose deaths, which investigators suggested was due to implementation of a more generous methadone take-home policy for those on maintenance therapy (Heinemann et al., 2000).

Diversion and misuse of buprenorphine have also been observed after its widespread diffusion, particularly in France.18 France launched an aggressive buprenorphine maintenance therapy program in 1996, in response to a rapid expansion of reported IDU-related HIV cases (Carrieri et al., 2003). The program, which allows general practitioners to prescribe high-dose buprenorphine maintenance treatment, treats an estimated 80,000 addicts (Carrieri et al., 2003).

One study examining illicit drug use and injection practices among patients enrolled in either methadone or buprenorphine maintenance treatment in France found that about 35 percent reported having used an illicit substance, 26 percent reported having injected drugs, and 15 percent reported having injected the agonist drug (buprenorphine or methadone) while in treatment. Risk of injection rose with the dose of buprenorphine, but this was not observed in patients on methadone treatment (Guichard et

18

In response to concerns about diversion and misuse of buprenorphine, France is considering a controversial proposal to reclassify buprenorphine as a narcotic. The effect that this measure, if implemented, would have on treatment access and availability is unclear. [Online]. Available: http://opiateaddictionrx.info/whatsnew.asp?id=1186 [accessed July 31, 2006].

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

al., 2003). Despite the relatively high prevalence of injection buprenorphine abuse among these patients, it is not clear whether buprenorphine maintenance increased the risks in these patients. It is possible that maintenance treatment may have reduced overall injection drug use in the population treated as well as the frequency or dangers associated with injection drug use even in those who continued injection drug use while being maintained on buprenorphine.

In a cross-sectional study of a sample of IDUs recruited from pharmacies, needle-exchange programs, and vending machine sites in France, 34 percent of respondents reported occasionally injecting buprenorphine, and 24 percent reported injecting only buprenorphine in the past 6 months (Obadia et al., 2001). In a cohort study of 114 HIV-infected IDUs, 28 percent reported buprenorphine injection misuse during the study period. Analysis showed that buprenorphine injectors were more likely to be multiple drug users and depressed, and less likely to be receiving antiretroviral treatment (Carrieri et al., 2003). In another study, nearly 50 percent of drug addicts interviewed in a cross-sectional survey reported injecting buprenorphine (Varescon et al., 2002).

One major strategy for reducing misuse and diversion of buprenorphine has been the development of a tablet combining buprenorphine and the opioid antagonist naloxone (Suboxone). The combination drug is currently being used in several countries. When the combination tablet is taken sublingually as prescribed, all the buprenorphine but very little naloxone is absorbed, so the naloxone does not have any clinical effects or interfere with the effects of buprenorphine (Kosten et al., 1990; Mendelson et al., 1999). However, when the buprenorphine/naloxone combination is dissolved and then injected, the naloxone takes full effect and will precipitate withdrawal symptoms for people who are dependent on heroin or other opioids (Mendelson et al., 1999; Elkader and Sproule, 2005). By causing withdrawal in heroin-dependent individuals, the combination drug offers better protection against misuse than the mono-buprenorphine tablet, but it is not a foolproof solution (Comer and Collins, 2002). When injected, the naloxone reduces the pleasurable or reinforcing effects of the buprenorphine only partially (Comer and Collins, 2002). And because buprenorphine binds more tightly to opiate receptors than naloxone, injected naloxone may not precipitate withdrawal in buprenorphine-dependent individuals (Kosten et al., 1990; Mendelson et al., 1999). As a result, the combination product may be abused, especially by individuals who are not physically dependent on heroin or other opioids, or by individuals who are physically dependent on buprenorphine.

There are clear societal-level tradeoffs between making opioid agonists more available, less costly to administer, and less burdensome on patients (such as through take-away doses and physician prescriptions) and reduc-

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

ing diversion and misuse. Specifically, increasing the number or proportion of opioid dependent individuals who are treated with opioid agonist maintenance treatment and increasing the retention of these patients in treatment increases the public benefits of opioid agonist maintenance treatment with regard to reductions of illicit opioid use, drug-related HIV risk behaviors, and HIV transmission.

A recent study in Australia (Ritter and Di Natale, 2005) examined this tradeoff by comparing methadone take-away policies and rates of methadone injection across six states. The study found that states with more restrictive take-away policies had lower reported rates of methadone injection. However, the investigators also found that methadone injection rates varied substantially among states with similar take-away policies. Factors that appear to be important include not only take-away policies but also drug preference, drug availability, treatment availability, and the amount of treatment coverage. This study illustrates the importance of taking into account both the benefits and the risks when making policy decisions on access to opioid agonist treatments.

Based on this evidence, the Committee concludes:

Conclusion 2-11: Strategies to limit diversion of opioid agonist medications—such as limiting the number of physicians who can prescribe the medication or directly observing patients while they ingest the medication—may increase the costs of treatment, and the costs to and burdens on patients, and may thus limit the dissemination of opioid agonist maintenance treatment. Countries’ policies and regulations regarding opioid agonist maintenance treatment should balance the potentially competing goals of increasing the accessibility and utilization of opioid agonist maintenance treatment and reducing the likelihood of diversion of agonist maintenance medications.

OPIOID ANTAGONIST PHARMACOTHERAPY

Opioid antagonist medication is another treatment option for opioid-dependent individuals who will not accept or cannot access opioid agonist maintenance therapy. Naltrexone is the most commonly used and widely studied opioid antagonist medication used to help the individual maintain long-term abstinence from opioids following detoxification.19 Studies show high relapse rates among opioid-dependent patients who simply undergo

19

The shorter-acting opioid antagonist medication, naloxone, is widely used to treat overdose.

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

detoxification and are not provided additional pharmacological or psychosocial treatments (IOM, 1990). Moreover, by lowering tolerance, detoxification appears to raise risks of overdose mortality among those who resume opioid use (Strang et al., 2003). As discussed later in this chapter, psychosocial interventions have little efficacy for opioid-dependent patients who are not receiving pharmacotherapy.

Oral naltrexone provides relatively long-lasting (up 1–3 days depending on dose) blockade of euphoric or rewarding effects of heroin or other opioids, and thus may help prevent resumption of opiate use (O’Brien and Kampman, 2004). New long-acting, injectable formulations of naltrexone produce adequate opioid blockade for up to 1 month (Dunbar et al., 2006). Before beginning naltrexone treatment, patients must be detoxified (medically withdrawn from heroin or other opioids), because naltrexone will precipitate severe withdrawal symptoms in people physically dependent on opioids (O’Brien and Kampman, 2004). Naltrexone binds tightly to opiate receptors, but does not activate them or have any rewarding, mood-altering, or euphoric effects, or lead to withdrawal symptoms when it is discontinued (O’Brien and Kampman, 2004). Because naltrexone’s blockade of opiate effects can be overridden by sufficiently large doses of opioids, naltrexone decreases but does not eliminate the risk of opioid overdose (O’Brien and Kampman, 2004). Patients who discontinue naltrexone are at greater risk for overdose if they resume opioid use (O’Brien and Kampman, 2004; Digiusto et al., 2004).

Despite strong pharmacological evidence and theoretical potential for naltrexone, evidence regarding its efficacy in controlled clinical trials is inconclusive. High attrition (premature discontinuation of treatment) is common with naltrexone treatment, and that complicates evaluation of its efficacy (Minozzi et al., 2006). The effectiveness of naltrexone in clinical practice, and consequently also the impact of naltrexone treatment for reducing drug use and HIV transmission on a large scale in the population of opioid-dependent individuals, has also been limited by high attrition, the relatively limited patient appeal of naltrexone, and the need for medically supervised withdrawal and a period of sustained abstinence before treatment begins (Kirchmayer et al., 2003).

In a recent Cochrane review (Minozzi et al., 2006), investigators conducted a meta-analysis of 10 RCTs comparing the efficacy of naltrexone treatment vs. placebo and other psychosocial treatments in preventing relapse in opioid-dependent persons after detoxification. Some of the studies compared naltrexone plus behavioral therapy with placebo plus behavioral therapy, or with behavioral therapy alone.

Four of the studies were conducted in the United States, two in Israel, and one each in Spain, China, Russia, and Germany. Two studies had adequate allocation concealment (Krupitsky et al., 2004; Lerner et al.,

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

1992). Seven of the ten trials were double-blind controlled trials (Curran and Savage, 1976; Guo et al., 2001; Hollister, 1978; Krupitsky et al., 2004; Lerner et al., 1992; San et al., 1991; Shufman et al., 1994), and three were not (Cornish et al., 1997; Ladewig, 1990; Rawson et al., 1979). Naltrexone dosage and frequency of administration varied by study.

All trials were conducted on an outpatient basis. The mean duration of trial length was 6 months, with a range of 1 to 10 months. The meta-analysis did not include data from one of the larger studies (Hollister et al., 1978) because the authors did not specify the number of participants in each treatment group.

Primary outcomes examined in the Cochrane meta-analysis included successful retention in treatment, opioid use during treatment, and relapse rates at follow-up. Secondary outcomes included side effects and reincarcerations during the study period. The analysis found that naltrexone treatment combined with psychosocial therapy was more efficacious than placebo alone, or placebo plus psychosocial, in reducing heroin use during treatment (RR 0.72; 95% CI: 0.58–0.90). However, the statistical significance of the results disappeared in comparisons of naltrexone therapy alone vs. placebo (RR 0.79; 95% CI: 0.59–1.06). Naltrexone plus psychosocial therapy was more effective than psychosocial treatment alone in preventing reincarceration during the study period (RR 0.50; 95% CI: 0.27–0.91). Naltrexone did not have a statistically significant benefit on retention in treatment, side effects, or relapse results at follow-up for any of the comparisons.

Johansson and colleagues (2006) conducted a recent meta-analysis of 15 RCTs comparing naltrexone with control populations. The authors found significant heterogeneity in the efficacy of naltrexone across trials. Treatment retention was the key explanatory variable for this heterogeneity. While naltrexone-treated groups had significantly fewer opioid-positive urine tests than controlled counterparts, this effect was only seen in the patient subgroup with high treatment retention. Contingency management20 (see next section on psychosocial interventions) was found to increase both retention and naltrexone use.

One RCT published since these reviews examined the efficacy of naltrexone with and without fluoxetine in preventing relapse among 280 heroin addicts in St. Petersburg, Russia. All patients received drug counseling and had involvement from parents or significant others. At 6 months,

20

Contingency management entails consistently rewarding patients (e.g., with monetary vouchers or other salient positive reinforcers) who remain abstinent or successfully complete other verifiable treatment objectives, and withholding rewards when a patient does not abstain (or successfully accomplish other specified objectives).

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

the number of people in the naltrexone treatment group who remained in treatment and were relapse-free was two to three times greater than the number of patients in the naltrexone placebo group (OR=3.5; 95% CI: 1.96–6.12). Adding fluoxetine did not improve outcomes. Retention was still a problem in this study, but reportedly less than in prior U.S. studies. The study found a decrease in HIV risk behaviors, psychiatric symptoms, and overall adjustment among patients who remained in treatment and did not relapse, although the possibility of self-selection bias cannot be excluded because follow-up was possible on only 40 percent of those who dropped out of treatment.

Several studies evaluating naltrexone in special populations—including patients on supervised probation (Cornish et al., 1997), or opioid-addicted physicians or lawyers (Tennant et al., 1984; Washton et al., 1984) whose ability to continue to work is contingent on abstinence—provide evidence that naltrexone may be efficacious under certain circumstances. Naltrexone has also been suggested as a potential intervention option in Russia, because opioid agonist maintenance treatment is illegal, and because many heroin addicts are young people who live with their parents who can oversee their medication adherence (Krupitsky et al., 2004, 2006). These studies suggest that naltrexone may be efficacious when used in circumstances where patients’ medication adherence and treatment retention can be closely monitored and facilitated.

Some studies also suggest that the efficacy of naltrexone can improve when it is combined with behavioral family therapy (O’Farrell and Fals-Stewart, 2002; Krupitsky et al., 2006) or contingency management (Carroll et al., 2002). New long-acting, injectable formulations may also improve the efficacy and effectiveness of naltrexone in clinical practice, as patients would be protected for several weeks after the last injection, providing enough time for clinics to reengage patients in treatment and provide the next dose before they relapse (Dunbar et al., 2006). However, the efficacy of these formulations has not yet been systematically evaluated.

Based on this evidence, the Committee concludes:

Conclusion 2-12: While there is strong pharmacologic evidence that naltrexone blocks opiate effects, its efficacy in controlled clinical trials is inconclusive. Efficacy and effectiveness studies of naltrexone treatment have been limited by problems with high patient attrition and the limited appeal of naltrexone. Studies suggest that naltrexone may be efficacious when used in circumstances where patients’ medication adherence and treatment retention can be closely monitored and facilitated.

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

PHARMACOTHERAPIES FOR STIMULANT DEPENDENCE

No pharmacological treatments have been found to be consistently efficacious in treating stimulant dependence. The National Institute on Drug Abuse in the United States is conducting a major research effort to identify effective pharmacotherapies for cocaine dependence (Vocci and Elkashef, 2005). Several studies suggest that disulfiram, an aversive drug therapy used to help prevent relapse among alcoholics, has potential as a treatment for cocaine use (Suh et al., 2006; Vocci and Elkashef, 2005). A number of randomized controlled trials of disulfiram support its efficacy in reducing cocaine and alcohol use and improving treatment retention among non-alcoholic cocaine-dependent and cocaine-alcohol dependent people (Higgins et al., 1993; Carroll et al., 1998, 2000). A recent study found that the benefits of disulfiram were strongest for cocaine users who did not have concurrent alcohol dependence, or who fully abstained from drinking during treatment (Carroll et al., 2004). Disulfiram has also been shown to reduce cocaine use among cocaine-dependent people enrolled in opioid agonist therapy, suggesting the possibility of combining pharmacotherapies (Petrakis et al., 2000; George et al., 2000). However, potential liver toxicity, nerve toxicity, and serious safety concerns about disulfiram-alcohol interactions, especially if cocaine is also used, may limit its use (Chick, 1999; Enghusen et al., 1992; Suh et al., 2006). Disulfiram is not approved by the U.S. Food and Drug Administration or other regulatory agencies for treatment of cocaine dependence.

Several other medications, including baclofen, modafinil, tiagabine, and topiramate, have also shown initial efficacy in reducing cocaine use in controlled clinical trials of cocaine-dependent patients. However, confirmatory trials are needed to replicate these results (Vocci and Elkashef, 2005). Current evidence does not support the clinical use of dopamine agonists, carbamazepine, and antidepressants for treating cocaine dependence (Soares et al., 2003; Lima Reisser et al., 2002; Lima et al., 2003).

Compared with the extensive research on pharmacotherapies for treating heroin and cocaine dependence, research on pharmacotherapies for dependence on amphetamine-type stimulants (e.g., methamphetamine) has only recently increased (Colfax and Shoptow, 2005). While several observational studies have examined the effects of stimulants prescribed to treat methamphetamine use, the only RCT testing the efficacy of a stimulant agent, dextroamphetamine, found no significant difference between the treatment and placebo arms, although both reduced their methamphetamine use (Colfax and Shoptow, 2005). A Phase II trial to treat methamphetamine dependence with buproprion, an antidepressant, is under way (Colfax and Shoptow, 2005). Phase I trials of vigabatrin, an anticonvulsant, showed decrease use of methamphetamine among those completing the trial, but attrition was high (Colfax and Shoptow, 2005). Randomized

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

controlled trials of other pharmacological agents21 found no effects on the use of methamphetamine or amphetamine-type stimulants (Srisurapanont et al., 2001; Rawson et al., 2002; Colfax and Shoptaw, 2005). Because of the widespread problem of methamphetamine abuse in many areas of the world, particularly Southeast Asia, additional research on pharmacotherapies for stimulant abuse is needed.

Based on this evidence, the Committee concludes:

Conclusion 2-13: No pharmacotherapy has been found to be consistently efficacious in treating stimulant dependence. There is modest to moderate evidence for the efficacy of disulfiram in reducing cocaine use, but liver toxicity, nerve toxicity and serious safety concerns related to potential disulfiram-alcohol-cocaine interactions may limit its value as a potential treatment. There is weak evidence regarding the efficacy of other pharmacological treatments for treating cocaine dependence. Research on pharmacotherapies for amphetamine-type stimulants has been limited and no effective therapies have been identified. More research is needed to further develop and define effective approaches to treat stimulant dependence.

EFFICACY AND EFFECTIVENESS OF PSYCHOSOCIAL INTERVENTIONS

A second major approach to drug treatment involves psychosocial interventions, which include a broad range of psychological and behavioral strategies, used either alone or in combination with pharmacotherapies and other medical or social interventions (Mayet et al., 2004). Psychosocial interventions may be provided with varying levels of intensity and frequency, for varying durations, and using a variety of approaches in outpatient treatment programs, partial hospital programs, in-hospital or residential programs. Psychosocial interventions may be delivered in individual or group settings, and may also include family members in the treatment in order to address family functioning (e.g., behavioral family therapy). Because proven pharmacological interventions are only available for treatment of opioid dependence22 and not for stimulants or other injectable drug

21

Agents that have been tested include: fluoxetine, a serotonin reuptake inhibitor; imipramine and desipramine, tricyclic antidepressants; amlodipine, a calcium channel blocker; and ondansetron, a seotonergic antagonist (Srisurapanont et al., 2001; Colfax and Shoptaw, 2005).

22

The focus of this report is on injecting drug users, and opiates are the only injectable drugs for which pharmacological treatments are available.

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

classes, psychosocial approaches are the primary treatment option for individuals dependent on these substances.

In this section, the Committee reviews the evidence regarding the effectiveness of the major psychosocial approaches to drug dependence treatment. These include four specific behavioral interventions (contingency management, community reinforcement approach, cognitive behavioral therapy, and motivational interviewing) as well as a collection of program models that include therapeutic communities, narcotics or drug anonymous programs (12-step programs), and chemical dependency programs (see Box 2.2 for a description of interventions). Evaluations of psychosocial programs are complicated by the significant heterogeneity of interventions and patient populations across sites.

Behavioral Interventions

Contingency Management

Contingency management (CM) has been extensively studied and shown to be effective in the treatment of stimulant-dependent individuals. CM relies on a variety of rewards, including monetary vouchers that can be redeemed for goods and services if the patient’s urine tests are free of illicit drugs, social rewards, or for methadone-maintained patients with co-occurring stimulant dependence, take-home methadone doses contingent on abstinence. When monetary vouchers are provided, the voucher amount typically rises with the number of consecutive drug-free urine tests, but starts over at a low amount if a person has a drug-positive test. The cumulative sum of the vouchers can reach several thousand dollars for long periods of abstinence. A lower-cost alternative—in which patients can draw from a prize lottery—has also been evaluated and is discussed below (Peirce et al., 2006; Petry and Martin, 2002).

A number of studies have shown the efficacy of CM for drug use and other outcomes among individuals with primary dependence on stimulants (Higgins et al., 1991, 1993, 1994, 2000; Petry et al., 2004), and among individuals who are dependent on both opiates and stimulants and receiving methadone (Piotrowski et al., 1999; Schottenfeld et al., 2005; Peirce et al., 2006). A lower-cost, prize-based CM procedure has also been found efficacious in treating primary cocaine dependence (Peirce et al., 2006) and cocaine dependence in opioid-dependent patients treated with methadone maintenance (Petry and Martin, 2002).

While researchers have studied the efficacy of CM among cocaine users extensively, the approach has not been as well-studied among users of other stimulants, such as methamphetamine. One study conducted in the United States found that CM interventions were efficacious in reducing metham-

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

BOX 2-2

Psychosocial Interventions for Drug Dependence Treatment

Specific Behavioral Interventions


Contingency management (CM) entails consistently rewarding patients (e.g., with monetary vouchers or other salient positive reinforcers) who remain abstinent or successfully complete other verifiable treatment objectives, and withholding rewards when a patient does not abstain (or successfully accomplish other specified objectives) (Higgins et al., 1991, 1993, 1994, 2000).

Cognitive behavioral therapy (CBT) teaches patients to recognize the environmental, interpersonal, stress-related, and psychological triggers—or cues—that lead to craving or relapse and to make lifestyle changes that support abstinence. Patients are also taught to identify the behavioral chains that lead to relapse and the coping skills to manage craving without relapse, and to avoid high-risk situations (Carroll et al., 1994).

Community reinforcement approach (CRA) is based on the theory that certain drug-related reinforcers (e.g., the positive drug effects or the social relationships organized around drug use) and a lack of non-drug-related alternatives maintains dependence. Thus, behavioral counseling is used to help patients develop or enhance rewarding activities, work, friendships, and other social interactions unrelated to drug use. The counseling also incorporates all the components of cognitive behavioral therapy. Patients are also provided vocational counseling and job-seeking skills, and helped to obtain employment or engage in other productive, nondrug-related activities (Higgins et al., 1991, 1993, 1994, 2000).

Motivational interviewing (MI) is a brief intervention that helps patients identify and resolve areas of ambivalence about continuing or ceasing drug use, thereby enhancing their desire or motivation to change. This strategy is based on the

phetamine use. In this randomized controlled trial (Shoptaw et al., 2005), 162 methamphetamine-dependent gay and bisexual men in Los Angeles were randomly assigned to one of four treatment conditions for 16 weeks. These conditions included standard cognitive behavioral therapy (CBT, n=40), contingency management (n=42), combined CBT and CM (n=40), and culturally adapted CBT (n=40). The study showed that interventions that included CM were most effective in retaining patients in treatment and reducing methamphetamine use. The CM condition produced the most methamphetamine-free urine samples, compared with standard CBT, followed by CBT plus CM, and then culturally adapted CBT.

Another recent RCT study evaluated the efficacy of sertraline23 and

23

Sertraline (Zoloft®) is a selective serotonin reuptake inhibitor commonly used to treat depression.

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

theory that there are five stages that people progress or cycle through in the process of achieving steady change: precontemplation (prior to recognition of problems associated with drug use or prior to beginning to think about stopping), contemplation (considering the benefits and losses of continuing drug use or stopping drug use), preparation for change, action (taking steps to stop drug use and then stopping use), and maintenance (preventing relapse) (Miller and Rollnick, 1992).

Matrix model is a manual-based treatment protocol that includes 16 weeks of CBT, family education groups, social support groups, and individual counseling, combined with weekly testing for alcohol and other drugs (Rawson et al., 2004).


Program Models


Therapeutic community model began in California in the 1950s and uses a structured residential community, organized around a peer hierarchy (with successful residents taking on increasing leadership roles) to confront patients about maladaptive behaviors and encourage and teach patients to cope with disappointments, loss, anger and other stressors without resorting to drug use or other maladaptive behaviors (IOM, 1990).

Chemical dependency model derives from a hospital-based approach to treating alcoholism that emphasizes 12-step recovery, developed in Minnesota in the 1960s, and therefore often referred to as the Minnesota model (IOM, 1990).

12-step recovery approaches (e.g., Narcotics Anonymous) use peer-led recovery groups to encourage addicts to acknowledge their addiction, recognize addiction as a disorder with medical, psychological, and spiritual components; these groups support addicts to take steady steps toward recovery by following the guiding principles initially established for Alcoholics Anonymous (IOM, 1990).

contingency management for the treatment of methamphetamine dependence among a group of male and females from the west coast of the United States (Shoptaw et al., 2006). Participants (n=229) were randomized to one of four conditions for 12 weeks: (1) sertraline (50 milligrams twice a day) plus CM (n=61); (2) sertraline only (n=59); (3) placebo plus CM (n=54); or (4) placebo only (n=55). The findings did not support the use of sertraline, however, they did support the use of CM for treating methamphetamine dependence. The study found that a significantly higher proportion of participants in the CM conditions achieved three weeks of methamphetamine abstinence than those in the non-CM conditions

Although there is strong evidence regarding the efficacy of CM for treating cocaine dependence and moderate evidence from two RCTs of its efficacy for treating methamphetamine dependence, it has not been found to be efficacious for individuals who are addicted to opiates alone and who

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

are not enrolled in agonist maintenance treatment. One study (Katz et al., 2002) that examined the use of CM for treating opiate-dependent individuals not on methadone had negative findings. This study compared two groups of opiate-dependent individuals referred from local detoxification units who were randomly assigned to either a voucher (n=29) or a no-voucher (n=23) condition. Both groups also received intensive cognitive behavioral therapy. Participants assigned to voucher could receive more than $1,000 for submitting urine samples that were both opiate and cocaine free.

The study found no differences between the voucher and no-voucher groups in treatment retention, number of opiate and cocaine-negative urines, or longest periods of abstinence. Retention in both groups averaged less than 40 days, of 180 days of treatment planned. The average maximum period of consecutive abstinence in both groups was less than 17 days, and only 21 percent of patients assigned to vouchers (and 9 percent of those assigned to the no-voucher control) remained abstinent for four or more weeks. Given the efficacy of CM in treating stimulant dependence (see below), and when combined with opioid agonist maintenance for treating co-occurring cocaine and opioid dependence, these negative findings point to the difficulty of treating opioid-dependent patients without opioid agonist maintenance treatment.

Cognitive Behavioral Therapy

In CBT, patients are taught to recognize the antecedents of drug use (e.g., environmental, interpersonal, stress-related, and psychological triggers—or cues—that lead to craving or relapse) and consequences of drug use and to learn skills and make behavioral changes to achieve and sustain abstinence. Patients are taught to identify the behavioral chains that lead to relapse, encouraged to make lifestyle changes that promote abstinence and avoid high-risk situations, and taught the coping skills to manage craving without relapse. Cognitive behavioral therapy has been evaluated for the treatment of a variety of addictive disorders, including alcohol, cocaine, nicotine, and marijuana dependence. Findings from several RCTs provide support for the efficacy of CBT for treating cocaine dependence, although differences in the outcome measures utilized, comparison treatments, and study methodologies complicate systematic comparison (Maude-Griffin et al., 1998; Monti et al., 1997; McKay et al., 1997; Carroll et al., 1994). A recent RCT found CBT to be more efficacious than interpersonal psychotherapy in reducing cocaine use (Carroll et al., 2004). Results of several RCTs indicate that CBT effects persist after cessation of counseling (Rawson et al., 2002; O’Malley et al., 1996; Carroll et al., 1994 2000).

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Community Reinforcement Approach

Most studies of the community reinforcement approach have been conducted with cocaine-dependent individuals and have bundled CRA counseling with contingency management and disulfiram treatment for individuals with co-occurring alcohol problems (Higgins et al., 1991, 1993, 1994, 2000). One RCT found that CRA (including CM) was more efficacious than CM alone in retaining individuals in treatment and keeping them abstinent from cocaine (Higgins et al., 2003; Roozen et al., 2004), supporting the efficacy of the CRA counseling components over and above CM.

Motivational Interviewing

Motivational interviewing uses an empathic, non-confrontational approach to increase patients’ recognition of the harmful effects or consequences of their drug use and their motivation and resolve to reduce or abstain from drugs (Miller and Rollnick, 1992). Motivational interviewing or motivational enhancement treatment has been investigated as a brief, stand-alone treatment for problem drinking and alcohol dependence. Several RCTs support its efficacy for reducing heavy drinking in problem drinkers who are not alcohol dependent and indicate that its efficacy for treating alcohol dependence is comparable to CBT or 12-step facilitation, a counseling approach designed to encourage patients to become involved in and utilize effectively 12-step recovery groups (Sellman et al., 2001; Project MATCH Research Group, 1998; Burke et al., 2003). Motivational interviewing has not been as thoroughly investigated for treating stimulant or opioid dependence, and promising findings from preliminary studies (Stotts et al., 2001; Secades-Villa et al., 2004) have not yet been validated with larger RCTs (Rohsenow et al., 2004).

Individual Counseling Promoting Utilization of 12-Step Recovery Programs and Involvement in the Tasks and Goals of 12-Step Recovery Programs

Twelve-step facilitation and the individual drug counseling utilized in the National Institute on Drug Abuse (NIDA) multi-site, randomized clinical trial of psychosocial treatments for cocaine dependence promote involvement in 12-step recovery programs and utilization of the strategies, goals, and principles of these recovery groups. In the NIDA multi-site cocaine collaborative treatment study, adding individual counseling to group drug counseling improves outcomes (addiction severity index composite score and length of time abstinent) for cocaine users compared to patients receiving group counseling only or group counseling combined with indi-

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

vidual cognitive therapy or individual interpersonal therapy (Crits-Christoph et al., 1999).

Matrix Model

The matrix model is an intensive program that combines several of the above treatments. It is a manual-based treatment protocol that includes 16 weeks of CBT, family education groups, social support groups, and individual counseling, combined with weekly testing for alcohol and other drugs.

In the largest clinical trial (Rawson et al., 2004) of treatment for methamphetamine dependence, 978 participants were randomly assigned to either treatment as usual or a 16-week treatment based on the matrix model at eight community outpatient settings in the western United States. Because the intention was to compare the matrix model with real-world treatment, the treatment-as-usual programs were not standardized. Instead, they encompassed a range of programs with varying approaches and intensity, including a “best available option” and a “minimal contact program.”

Overall, participants assigned to the matrix model attended more treatment sessions (except at a drug-court site) and remained in treatment significantly longer (five of the eight sites). Participants assigned to the matrix model provided more methamphetamine-free urine samples during treatment (except at the drug-court site) and had longer periods of methamphetamine abstinence. However, the differences in the number of methamphetamine-free urine samples were significant at only one site, and the differences in duration of abstinence were significant at only two sites. Participants at all sites showed significant improvement in drug use and functioning scores at discharge and 6 months post-admission follow-up, compared with baseline levels. The matrix approach was not superior on these measures.

Based on this evidence, the Committee concludes:

Conclusion 2-14: Strong evidence from a significant number of well-done randomized, controlled trials shows that CM is associated with longer retention in treatment and time abstinent from stimulants among individuals who are primarily dependent on stimulants, and among individuals who are dependent on both stimulants and opiates and enrolled in agonist maintenance therapy. CM has not been found to be efficacious for individuals who are addicted to opiates but who are not enrolled in agonist maintenance therapy. While most studies have examined the efficacy of CM for cocaine users, two randomized clinical trials show that CM is effective in reducing methamphetamine use.

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

Conclusion 2-15: There is modest evidence of efficacy of several other behavioral approaches to addressing stimulant abuse. These include combined individual drug counseling and intensive group drug counseling, cognitive behavioral therapy, and community reinforcement combined with contingency management. There is weak evidence regarding the effectiveness of motivational interviewing and the matrix model for treatment of stimulant or other drug dependence. No psychosocial intervention alone (in the absence of pharmacotherapies) has been shown to be consistently efficacious in treating opioid dependence.

Therapeutic Communities, Narcotics or Drug Anonymous Programs, and Chemical Dependency Programs

The Committee also reviewed evidence regarding the effectiveness of Narcotics Anonymous (NA) and other self-help or 12-step recovery programs; therapeutic communities (TC), which involve longer-term residential treatment; and chemical dependency programs, which are 12-day or 28-day inpatient and residential approaches (IOM, 1990). The Committee recognizes that many individuals who have achieved lasting recovery from addiction to heroin or other opioids and other drugs have used NA, chemical dependency programs, or TC to initiate and support their recovery. Nevertheless, the efficacy and effectiveness NA—alone or in combination with other approaches—has not been systematically evaluated.

A 1990 IOM report, Treating Drug Problems, reached the following conclusion about NA: “There are virtually no data to answer critical questions regarding independent self-help fellowship groups such as Narcotics Anonymous and Cocaine Anonymous” (p. 135). This report also noted that NA and other Drug Anonymous groups are often “in essence part of the environmental baseline over which the incremental effects of the more formal treatments must be measured” (p. 135).

High relapse rates following detoxification—even when patients are given drug counseling and referred to NA—suggest that for the vast majority of addicts, any given episode of detoxification, drug-free counseling, or NA is not likely to lead to sustained abstinence or recovery. Over time, repeated relapse and treatment episodes may lead to sustained recovery for a growing number of individuals, but data from long-term, naturalistic follow-up studies of treated addicts document the risks of addiction and the difficulties of achieving sustained recovery.

Hser and colleagues (2001) reported the status of 581 heroin-addicted men more than 30 years after their admission to compulsory drug abuse treatment. Nearly half of the men had died within this period—most as a result of drug overdose, suicide, violence, accidents, infections, or chronic

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

liver disease. The mortality rate greatly exceeded that expected for men in their 20s and 30s at the time of the cohort assembly. After more than 30 years, only 23 percent of the men were not using illicit opiates. Reflecting the persistence of addiction and the high risk of relapse, only about one of six of those who were continuing to use 20 years after admission—and about the same proportion of those who had been abstinent for less than 5 years at that time—were abstinent after another 10 years. One-quarter of those who had been abstinent for more than 15 years at the 20-year follow-up also relapsed over the next 10 years.

It is important to distinguish TC from long-term detention or imprisonment. There are limited or no data from controlled clinical trials regarding the efficacy of long-term detention for preventing post-detention relapse. Naturalistic studies from many countries report exceedingly high relapse rates following prison release. For instance, relapse rates among inmates in government-run drug rehabilitation centers in Malaysia reportedly range from 70 to 90 percent (Reid et al., 2005; Scorzelli, 1992). In contrast, however, follow-up studies of patients treated in a TC consistently report that longer time in treatment is associated with higher proportion of patients abstinent at follow-up (IOM, 1990). This may be due to self-selection: that is, patients with poor prognosis may drop out of treatment early, while patients with good prognosis may stay in treatment.

The major limitation in evaluating the effects of TC relative to other treatments is the high attrition rate. As noted in the 1990 IOM report, “Conclusions about the effectiveness of TCs are limited by the difficulties of applying standard clinical trial methodologies to a complex, dynamic treatment milieu and a population resistant to following instructions. Randomized trials or natural experiments in the community, which would permit a well-controlled comparison of clients admitted to TC treatment versus an equivalent group … are not feasible or appropriate; when attempted, such experimental protocols have failed” (see Bale et al., 1980, p. 153).

Consequently, data on the effectiveness of TCs are derived mainly from prospective cohort studies of patients entering TCs or other types of drug treatment. Most such studies show a strong association between length of time in treatment and better outcomes at long-term follow-up (IOM, 1990). Patients staying in TCs longer than 90 days have better treatment outcomes (in terms of drug use, employment, and criminal activity), and the longer patients remain in treatment beyond 90 days, the better the outcomes. Data from the U.S.-based Treatment Outcome Prospective Study indicated that staying 1 year or more in a TC was significantly associated with better drug, employment, and criminal activity outcome measures at 1-year post-treatment follow-up. Data from the Drug Abuse Treatment Outcome Studies, a longitudinal study of 96 treatment programs in the United States, also

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

supported a relationship between treatment duration and improved outcomes. Data collected at 5-year follow-up showed that staying more than 6 months in long-term residential treatment was associated with significant reductions in drug use and illegal activities, and significant increases in full-time employment (Hubbard et al., 2003).

Thus findings from these prospective cohort studies regarding the effectiveness of chemical dependency outpatient treatments are similar to the findings for TCs: “Clients who remain in treatment longer have better outcomes at follow-up than shorter term clients” (IOM, 1990, p. 168).

Based on this evidence, the Committee concludes:

Conclusion 2-16: There is relatively weak evidence regarding the effectiveness of therapeutic communities, chemical dependency programs, and drug anonymous treatments, but these are important treatment options for opioid-dependent individuals who will not accept or cannot access opioid agonist maintenance treatment, or for individuals dependent on other classes of drugs.


Conclusion 2-17: Studies have found that length of time in treatment in therapeutic communities, chemical dependency, or outpatient programs is the strongest predictor of positive treatment outcomes. However, the possibility of self-selection bias cannot be excluded.

Effects of Psychosocial Interventions on HIV-Related Outcomes

Stimulant-addicted individuals are at high risk for HIV transmission, primarily because of sexual risk behavior, including high-risk sex associated with stimulant use, and—for those who inject stimulants—injecting drug use. The Committee identified two reviews and meta-analyses that specifically examined the impact of psychosocial interventions on the HIV-related risks of injecting drug users. Both these studies suggest that psychosocial interventions have some positive effect on behavioral change (Prendergast et al., 2001; Gibson et al., 1998). However, it is difficult to interpret the findings of these reviews because the studies included different types of psychosocial interventions, drug users (stimulant and opiate users), and patient populations (residential, outpatient, methadone-maintained).

The recent meta-analysis by Prendergast and colleagues (2001) on the efficacy of adding psychosocial interventions targeting HIV risk reduction to drug counseling identified 18 studies comparing an intervention group and a comparison group. The results of the meta-analysis suggest that these added interventions may reduce overall HIV risk behavior and sexual risk behavior, and may increase HIV risk-reduction skills. However, the conclu-

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

sions of the review are weakened because of the heterogeneity of the interventions and the patient populations. Some studies included methadone-maintained patients, others included patients in hospital or residential programs, and still others included patients in outpatient programs.

Gibson et al. (1998) similarly reviewed 19 studies examining the effectiveness of individual counseling, HIV testing, group interventions, street outreach, and social intervention designed to change behavioral norms. The results of this analysis also pointed to a beneficial effect of psychosocial interventions on behavioral change. Again, however, the results of the analysis are limited because of the heterogeneous interventions and patient populations.

As noted, one study by Shoptaw and colleagues (2005) examined the effect of CM, standard CBT, and an intervention that integrates CBT with culturally tailored counseling targeting sexual risk behavior among methamphetamine-addicted men who have sex with men (gay-specific CBT, or GCBT) in the United States. Participants in the culturally adapted GCBT had statistically significant reductions in unprotected receptive anal intercourse in the first 4 weeks of treatment. Participants in all treatment conditions reported significantly reduced levels of unprotected anal intercourse and the number of sex partners from baseline to 16 weeks. Decreases in reported sexual risk behavior were maintained at 6-month and 12-month follow-ups. The study detected no statistically significant differences between groups.

Based on this evidence, the Committee concludes:

Conclusion 2-18: Weak to modest evidence shows that targeted psychosocial interventions are effective in reducing sex-related HIV risk behavior among stimulant-dependent individuals.

LINKS TO HEALTH AND SOCIAL SERVICES

Drug treatment services are often provided in specialized drug treatment clinics, that are typically separate from other health and social services (WHO et al., 2004). Opioid agonist treatments, particularly methadone, are highly regulated in many countries and administration may be limited primarily to licensed narcotic treatment programs. Some countries, particularly in Western Europe, have made physician office-based treatment of opioid agonist treatments widely available. Other drug treatment programs (e.g., chemical dependency, therapeutic communities) provided in outpatient, inpatient, or residential settings may incorporate or provide referrals to additional medical or social services, but the availability of these services varies substantially across sites (IOM, 1990).

Few studies have specifically examined whether participation in drug-

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

dependence treatment leads to increases in the use of needed health and social services. Several studies from the United States have examined whether delivery of outpatient primary care at the site of drug-dependence treatment reduces expensive visits to the emergency department and inpatient hospitalization, both of which are indicators of poor access to care and/or poor quality of care (Samet et al., 2001). A study by Friedmann et al. (2006) found that onsite primary care in drug treatment programs reduced emergency department and hospital use among patients in methadone maintenance and long-term residential programs. Laine and colleagues (2001) retrospectively examined the association between outpatient medical and drug abuse care with later hospitalizations. Both HIV-seropositive and HIV-negative IDUs receiving regular medical and drug abuse care had the lowest adjusted odds ratio (AOR) for hospitalization (AOR=0.76; 95% CI: 0.67–0.85 and AOR=0.73; 95% CI: 0.68–0.79, respectively), compared with IDUs receiving one type of care (medical or drug abuse) or no care. Turner and colleagues (2003) found that among HIV-infected drug users, the odds of repeated emergency department visits were increased for those not receiving long-term drug treatment (methadone maintenance or drug-free treatment).

In another study, Friedmann and colleagues (2003) examined whether onsite primary care influenced addiction severity and medical outcomes. Findings showed that after 12 months, patients who attended programs with onsite primary care had lower addiction severity compared with patients attending programs with no primary care. There was no significant difference in medical outcomes.

Finally, Laine et al. (2005) examined the association of services in drug-treatment clinics with repeated emergency department use. Repeated visits to emergency departments were less likely when medical services were provided onsite in low- to moderate-volume treatment clinics. In the United States, a multi-site research demonstration project is currently examining programs integrating buprenorphine maintenance treatment into HIV care settings, as certified primary care physicians can now prescribe buprenorphine.

Because of the high prevalence of HIV among injecting drug users, researchers have examined whether directly administered antiretroviral therapy (DAART) provided at methadone clinics could improve treatment adherence and outcomes among HIV-seropositive IDUs. A study by Lucas et al. (2006) at a methadone clinic in Baltimore in the United States showed that after 12 months, DAART participants were significantly more likely to achieve viral suppression than HIV-seropositive IDU patients receiving methadone, IDUs not receiving methadone, and non-IDU patients. Antiretroviral therapy was available to all patients. The results also suggest that DAART was feasible and acceptable to patients in a methadone clinic

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

setting. Furthermore, DAART has proven quite inexpensive and feasible in low-resource settings (IOM, 2005). A study by Moatti and colleagues (2000) in France showed that active IDUs were some five times more likely to be non-adherent in their HIV treatment than IDUs on buprenorphine maintenance treatment and former IDUs. There was no significant difference between the adherence of IDUs on buprenorphine and former IDUs.

Another reason for more closely integrating ART and opioid agonist maintenance treatment is that the two sets of drugs often have serious interactions that require careful dose adjustments and monitoring. There is a significant literature documenting interactions between opioid agonist maintenance drugs and other drugs, particularly those involving metabolism by liver cytochrome P450 3A4 such as antiretroviral medications. Several studies have demonstrated that some of the drugs used to treat HIV and associated illnesses affect metabolism of opioid agonist maintenance medications (Iribarne et al., 1998; McCance-Katz et al., 2001, 2003, 2006). Some antiretroviral medications increase the metabolism of methadone, and initiation of treatment with these medications in methadone maintained patients may lead to withdrawal symptoms if the methadone dose is not increased (McCance-Katz et al., 2003, 2006). Other antiretrovirals may inhibit metabolism of methadone or buprenorphine and lead to increased levels of the maintenance medication (McCance-Katz et al., 2003, 2006); in this case, if patients experience sedation, the opioid maintenance medication dosage may need to be reduced slightly. Opioid agonist maintenance medications may also interfere with the metabolism of the antiretroviral medication, necessitating adjustments of the antiretroviral medication dosage (McCance-Katz et al., 2006). Given the high prevalence of HIV among IDUs, such interactions need to be taken into consideration and may require additional monitoring.

These findings indicate that IDUs can benefit from further integration of or referrals to primary care, HIV care, and other social services. The model combining DAART with opioid agonist therapy suggests that it is beneficial and should be studied further. WHO et al. (2004) suggests that a clear and coherent service plan is required to address the large scale of problems and resource constraints in many countries facing an IDU-driven HIV epidemic. They suggest broad community-based programs should be explored as one option.

Based on this evidence, the Committee concludes:

Conclusion 2-19: Drug treatment services are not always well integrated with other health and social programs for drug users. Modest evidence from studies in the United States shows that providing basic primary care services as part of drug treatment reduces emergency department use and hospitalization among

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

IDUs (which are indicators of poor access to or quality of care). Evidence also indicates that providing directly administered anti-retroviral therapy to HIV-seropositive IDUs can improve adherence and treatment outcomes, but it is important to monitor potential drug interactions between antiretroviral medications and opioid agonist maintenance drugs. These findings indicate that IDUs can benefit from integrated drug treatment, HIV care, and other health and social services.

RECOMMENDATIONS

Based on its review of the evidence, the Committee makes the following recommendations:

Recommendation 2-1: Given the strong evidence of its effectiveness in treating opioid dependence, opioid agonist maintenance treatment should be made widely available where feasible. Such programs should include:

  • The necessary infrastructure to make treatment widely available (e.g., clinics, trained health workers) and a strategy to ensure sustainability.

  • Assurance of adequate dosage and treatment duration.

  • A balance between strategies to decrease diversion of treatment medication and strategies to disseminate the treatment.

  • An evaluation component to monitor treatment implementation, quality, and outcomes.

  • Monitoring of potential drug interactions between antiretroviral medications and opioid agonist maintenance drugs for HIV-infected IDUs.

Recommendation 2-2: Given the potential benefits and lack of harmful effects, the following treatments should also be made available as part of a multi-component treatment system, where feasible, but should include a rigorous evaluation component:

  • Naltrexone treatment for opioid-dependent patients interested in abstinence-oriented treatment.

  • Specific behavioral treatments (contingency management, cognitive behavioral therapy, community reinforcement approach, motivational interviewing, and individual drug counseling) for treating stimulant dependence.

  • Chemical dependency treatment, therapeutic communities, and Drug Anonymous groups for patients dependent on any drug class who are interested in abstinence-oriented treatment.

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

FUTURE RESEARCH

There is strong and consistent evidence that opioid agonist maintenance treatment reduces illicit opioid use and drug-related HIV risk factors, and modest evidence that such treatment protects against HIV infection. There is also strong evidence that higher doses of methadone and buprenorphine are more effective than lower doses in reducing illicit opioid use, and that longer duration of treatment is associated with greater treatment benefits. However, the optimal level of psychosocial interventions for patients receiving opioid agonist maintenance treatment, for patients with different treatment needs, and for reducing HIV risk behavior have not been established. These important areas require further research. While all opioid agonist medications used can be abused, research is also needed to evaluate the best strategies for reducing diversion and abuse while facilitating widespread coverage of patients in need of treatment. During the scaling up process for disseminating opioid agonist maintenance treatment and when opioid agonist maintenance treatment is widely available in a country, treatment outcomes are likely to vary across programs and sites and, within sites, among patients with differing characteristics. Health service delivery research can play an important role in identifying program characteristics or components associated with improved (or adverse) outcomes and also in identifying patient subgroups who respond well to standard interventions or who require additional treatments.

A variety of other approaches are often used to treat opioid dependence. However, the evidence regarding the efficacy and effectiveness of opioid antagonist maintenance treatment, specifically naltrexone, is weak to modest, and the evidence for psychosocial interventions alone in treating opioid dependence is weak. Little research has been done to evaluate the effectiveness of naltrexone treatment or psychosocial interventions alone for reducing HIV risk behavior or HIV transmission associated with opioid dependence. Nevertheless, some patients respond to these treatments, and some will not accept or cannot access opioid agonist maintenance treatment. These considerations support the importance of additional research aimed at identifying patient characteristics that could be used to predict good response to antagonist maintenance treatment or psychosocial treatments alone, or that could be used to improve the efficacy of these treatments.

Similar considerations apply to stimulant dependence, where there is an urgent need to develop and evaluate effective treatments. No pharmacological treatment has been consistently found efficacious in treating dependence on amphetamine-type stimulants. Strong evidence supports the efficacy of contingency management, but the feasibility and acceptability of this treatment in clinical practice settings is problematic. The evidence sup-

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

porting the efficacy of several other psychosocial treatments for stimulant dependence is modest. As with psychosocial treatments for opioid dependence, no studies have evaluated the effectiveness of psychosocial treatments other than contingency management for reducing HIV risk behavior or HIV transmission. Given the rising prevalence of amphetamine-type stimulant abuse worldwide, and its association with HIV transmission, studies of treatments for stimulant dependence are critical.

Recommendation 2-3: Given the relative weakness of the evidence, further research should occur on the following issues related to treatment for drug dependence:

  • The additional benefits and cost-effectiveness of adding psychosocial interventions to opioid agonist maintenance treatment for opiate-dependent people in high-risk countries, and the relative effectiveness of those interventions in particular cultural contexts and for particular patient subgroups.

  • Pharmacotherapies for stimulant abuse, particularly amphetamine-type stimulants which have emerged as a major problem in many parts of the world.

  • The effectiveness of naltrexone for different patient populations and in different settings.

  • The relative effectiveness of various psychosocial interventions in treating opiate dependence in places where opioid agonist maintenance therapy is not available or accessible.

  • Developing cost-effective and feasible alternatives to voucher-based contingency management approaches for treating stimulant dependence.

  • Effective strategies for reducing sex-related risk behavior of IDUs in treatment.

  • Optimal strategies for linking drug dependence treatment with health and social services.

CONCLUSION

In this chapter, the Committee reviewed the evidence of effectiveness of drug dependence treatment in reducing drug-use, drug- and sex-related HIV risk behaviors, and HIV seroconversion. The Committee’s findings and recommendations for policymakers and clinicians are summarized as follows:


For injecting opioid users seeking treatment: Opioid agonist maintenance treatment is the only consistently effective treatment for opioid dependence. Studies show that it reduces illicit opioid use, injection-related HIV risk

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

behaviors, and risk of HIV seroconversion among people with opioid dependence. Given the strong evidence of its effectiveness, opioid agonist maintenance treatment should be made widely available where feasible. The medication should be provided in sufficiently high doses and for a sufficient duration for therapeutic effects to occur. Programs should include adequate infrastructure, a plan for sustainability, and balance between strategies to decrease potential diversion and strategies to disseminate the treatment. Pharmacological treatments for opioid dependence do not have reliable or sustained effects on non-opiate use or on high-risk sexual behaviors. Clinicians and policymakers hoping to affect these behaviors will require other interventions and services to effect those changes.

Opioid antagonist medication is another pharmacological treatment option for opioid-dependent individuals who will not accept or cannot access opioid agonist maintenance therapy. Despite strong pharmacologic evidence and theoretical potential of naltrexone in blocking opiate effects, its efficacy in controlled clinical trials is inconclusive. Naltrexone is likely to be most successful for patients whose medication adherence and treatment retention can be closely monitored and facilitated. Additional research needs to be done regarding the effectiveness of naltrexone for different patient populations and in different settings.

Psychosocial interventions alone have not been shown to be consistently effective in treating opioid dependence. More research is needed on the additional benefits and cost-effectiveness of adding psychosocial interventions to opioid agonist maintenance treatment for opiate-dependent people in high-risk countries, and the relative effectiveness of those interventions in particular cultural contexts and for particular patient subgroups. More research is also needed on the relative effectiveness of various psychosocial interventions in treating opiate dependence in situations where opioid agonist maintenance therapy is not available.


For injecting non-opiate users seeking treatment: No pharmacotherapies have been found to be consistently efficacious in treating stimulant dependence. Contingency management is an efficacious treatment for stimulant dependence, but additional research is needed on the feasibility of its application outside of research settings. There is modest evidence of efficacy of other several behavioral or psychotherapeutic approaches in addressing stimulant abuse, including individual drug counseling and intensive group drug counseling, cognitive behavioral therapy, and community reinforcement combined with contingency management. Those seeking effective interventions for non-opioid users should consider behavioral or psychosocial interventions, but funders and policymakers are urged to collect rigorous evaluation data on those options if they are selected. Additional research should be done regarding pharmacotherapies for stimulant abuse,

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

particularly amphetamine-type stimulants, which have emerged as a major problem in many parts of the world. More research is also needed on developing cost-effective and feasible alternatives to voucher-based contingency management approaches for treating stimulant dependence outside of the research setting.


For injecting drug users not enrolled in treatment: The effectiveness of various strategies for drug users not in treatment, namely sterile syringe access programs and outreach and education, are discussed in Chapter 3.

Not all treatment options will work for all individuals. Specific treatments and their intensity, frequency, duration, and location would ideally be matched to the needs of individual patients. Patient-specific factors include the type and severity of abuse/addiction, co-occurring psychiatric or other drug disorders, co-morbid medical problems, treatment readiness and motivation, employment, family and social support, and involvement in the criminal justice system. These factors also affect treatment response, and studies need to evaluate whether differences in treatment outcomes result from differences in treatment or the characteristics of patients. Some studies suggest that matching specific treatment services to patients’ needs improves outcomes (Carise et al., 2005; Gurel et al., 2005). While policymakers should invest resources in the most effective and cost-effective treatments, it is important to have a range of treatment options available.

REFERENCES

Abbott PJ, Weller S, Delaney H, Moore B. 1998. Community reinforcement approach in the treatment of opiate addicts. American Journal of Drug and Alcohol Abuse. 24(1):17–30.

Amato L, Minozzi S, Davoli M, Vecchi S, Ferri M, Mayet S. 2004. Psychosocial combined with agonist maintenance treatments versus agonist maintenance treatments alone for treatment of opioid dependence. The Cochrane Database of Systematic Reviews. (4):CD004147.

Anglin MD, Speckart GR, Booth MW, Ryan TM. 1989. Consequences and costs of shutting off methadone. Addictive Behaviors. 14(3):307–326.

Auriacombe M, Fatséas M, Dubernet J, Daulouède JP, Tignol J. 2004. French field experience with buprenorphine. American Journal on Addictions. 13:S17–S28.

Avants SK, Margolin A, Kosten TR, Rounsaville BJ, Schottenfeld RS. 1998. When is less treatment better? The role of social anxiety in matching methadone patients to psychosocial treatments. Journal of Consulting and Clinical Psychology. 66(60):924–931.

Avants SK, Margolin A, Sindelar JL, Rounsaville BJ, Schottenfeld R, Stine S, Cooney NL, Rosenheck RA, Li SH, Kosten TR. 1999. Day treatment versus enhanced standard methadone services for opioid-dependent patients: A comparison of clinical efficacy and cost. American Journal of Psychiatry. 156(1):27–33.

Avants SK, Margolin A, Usubiaga MH, Doebrick C. 2004. Targeting HIV-related outcomes with intravenous drug users maintained on methadone: A randomized clinical trial of a harm reduction group therapy. Journal of Substance Abuse Treatment. 26:67–78.

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

Backmund M, Schutz CH, Meyer K, Eichenlaub D, Soyka M. 2003. Alcohol consumption in heroin users, methadone-substituted and codeine-substituted patients-frequency and correlates of use. European Addiction Research. 9:45–50.

Baker A, Heather N, Wodak A, Dixon J, Holt P. 1993. Evaluation of a cognitive-behavioural intervention for HIV prevention among injecting drug users. AIDS. 7(2):247–256.

Baker A, Kochan N, Dixon J, Wodak A, Heather N. 1995. HIV risk-taking behaviour among injecting drug users currently, previously and never enrolled in methadone treatment. Addiction. 90:545–554.

Bale RN, Van Stone WW, Kuldau JM, Engelsing TM, Elashoff RM, Zarcone VP Jr. 1980. Therapeutic communities vs methadone maintenance. A prospective controlled study of narcotic addiction treatment: Design and one-year follow-up. Archives of General Psychiatry. 37(2):179–193.

Bandura, A. 1994. Self-efficacy. In Ramachaudran VS, ed., Encyclopedia of Human Behavior Volume 4, pp. 71–81. New York: Academic Press. Reprinted in Friedman H, ed., 1998. Encyclopedia of Mental Health. San Diego: Academic Press.

Batki SL, Sorenson JL, Gibson DR, Maude-Griffin P. 1989. HIV-infected IV drug users in methadone treatment: Outcome and psychological correlates—a preliminary report. NIDA Research Monograph Series. 95:405–406.

Berson A, Gervais A, Cazals D, Boyer N, Durand F, Bernuau J, Marcellin P, Pegott C, Valla D, Pessayre D. 2001. Hepatitis after intravenous buprenorphine misuse in heroin addicts. Journal of Hepatology. 34:346–350.

Britton BM. 1994. The privatization of methadone maintenance: Changes in risk behavior associated with cost related detoxification. Addiction Research. 2(2):171–181.

Brooner R, Kidorf M, King V, Beilenson P, Svikis D, Vlahov D. 1998. Drug abuse treatment success among needle exchange participants. Public Health Reports. 113:483–489.

Burke BL, Arkowitz H, Menchola M. 2003. The efficacy of motivational interviewing: A meta-analysis of controlled clinical trials. Journal of Consulting and Clinical Psychology. 71:843–861.

Camacho LM, Barthoomew NG, Joe GW, Cloud MA, Simpson DD. 1996. Gender, cocaine and during-treatment HIV risk reduction among injection opioid users in methadone maintenance. Drug and Alcohol Dependence. 41:1–7.

Caplehorn JR, Dalton MS, Cluff MC, Petrenas AM. 1994. Retention in methadone maintenance and heroin addicts’ risk of death. Addiction. 89(2):203–209.

Carise D, Gurel O, McLellan AT, Dugosh K, Kendig C. 2005. Getting patients the services they need using a computer-assisted system for patient assessment and referral— CASPAR. Drug and Alcohol Dependence. 80(2):177–189.

Carrieri MP, Rey D, Loundou A, Lepeu G, Sobel A, Obadia Y. 2003. Evaluation of buprenorphine maintenance treatment in a French cohort of HIV-infected injecting drug users. Drug and Alcohol Dependence. 72(1):13–21.

Carroll, KM, Rounsaville BJ, Gordon LT, Nich C, Jatlow PM, Bisighini RM, Gawin FH. 1994. One year follow-up of psychotherapy and pharmacotherapy for cocaine dependence: Delayed emergence of psychotherapy effects. Archives of General Psychiatry. 51(12):989–997.

Carroll KM, Nich C, Ball SA, McCance-Katz E, Rounsaville BJ. 1998. Treatment of cocaine and alcohol dependence with psychotherapy and disulfiram. Addiction. 93:713–728.

Carroll KM, Nich C, Ball SA, McCance-Katz ER, Frankforter TF, Rounsaville BJ. 2000. One-year follow-up of disulfiram and psychotherapy for cocaine-alcohol abusers: Sustained effects of treatment. Addiction. 95:1335–1349.

Carroll KM, Sinha R, Nich C, Babuscio T, Rounsaville BJ. 2002. Contingency management to enhance naltrexone treatment of opioid dependence: A randomized clinical trial. Experimental and Clinical Pharmacology. 10(1):54–63.

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

Carroll KM, Renton LR, Ball SA, Nich C, Frankforter TL, Shi J, Rounsaville BJ. 2004. Efficacy of disulfiram and cognitive behavior therapy in cocaine-dependent outpatients: A randomized placebo-control trial. Archives of General Psychiatry. 61:264–272.

Chatham LR, Hiller ML, Rowan-Szal GA, Joe GW, Simpson DD. 1999. Gender differences at admission and follow-up in a sample of methadone maintenance clients. Substance Use and Misuse. 34(8):1137–1165.

Chick J. 1999. Safety issues concerning the use of disulfiram in treating alcohol dependence. Drug Safety. 20(5): 427–435.

Cicero TJ, Inciardi JA. 2005. Diversion and abuse of methadone prescribed for pain management. Journal of the American Medical Association. 293(3):297–298.

Clark N, Lintzeris N, Gijsbers A, Whelan G, Dunlop A, Ritter A, Ling W. 2002. LAAM maintenance vs methadone maintenance for heroin dependence. The Cochrane Database of Systematic Reviews. (2):CD002210.

Colfax G, Shoptaw S. 2005. The methamphetamine epidemic: Implications for HIV prevention and treatment. Current HIV/AIDS Reports. 2:194–199.

Comer SD, Collins ED. 2002. Self-administration of intravenous buprenorphine and the buprenorphine/naloxone combination by recently detoxified heroin abusers. Journal of Pharmacology and Experimental Therapeutics. 303(2):695–703.

Cornish JW, Metzger D, Woody GE, Wilson D, McLellan AT, Vandergrift B, O’Brien CP. 1997. Naltrexone pharmacotherapy for opioid dependent federal probationers. Journal of Substance Abuse Treatment. 14(6):529–534.

Courtnage PA. 1991. HIV/AIDS risk reduction through treatment of cocaine-dependent methadone patients: A multiaxial intervention. Dissertation Abstracts International. 52(11B), 0630.

Crits-Christoph P, Siquieland L, Blaine J, Frank A, Luborsky L, Onken LS, Muenz LR, Thase ME, Weiss RD, Gastfriend DR, Woody GE, Barber JP, Butler SF, Daley D, Salloum I, Biship S, Najavits LM, Lis J, Mercer D, Griffin ML, Moras K, Beck AT. 1999. Psychosocial treatments for cocaine dependence. Archives of General Psychiatry. 56:493–502.

Curran S, Savage C. 1976. Patient response to naltrexone: Issues of acceptance, treatment effects, and frequency of administration. NIDA Research Monograph. (9):67–69.

Darke SG, Ross JE, Hall WD. 1995. Benzodiazepine use among injecting heroin users. The Medical Journal of Australia. 162(12):645–647.

Digiusto E, Shakeshaft A, Ritter A, O’Brien S, Mattick RP; The NEPOD Research Group. 2004. Serious adverse events in the Australian National Evaluation of Pharmacotherapies for Opioid Dependence (NEPOD). Addiction. 99:450–460.

Dolan KA, Shearer J, MacDonald M, Mattick RP, Hall W, Wodak AD. 2003. A randomized controlled trial of methadone maintenance treatment versus wait list control in an Australian prison system. Drug and Alcohol Dependence. 72:59–65.

Dole VP, Robinson JW, Orraca J, Towns E, Searcy P, Caine E. 1969. Methadone treatment of randomly selected criminal addicts. New England Journal of Medicine. 280(25):1372– 1375.

Dunbar JL, Turncliff RZ, Dong Q, Silverman BL, Ehrich EW, Lasseter KC. 2006. Single- and multiple-dose pharmacokinetics of long-acting injectable naltrexone. Alcoholism, Experimental and Clinical Research. 30(3):480–490.

Elkader A, Sproule B. 2005. Buprenorphine: Clinical pharmacokinetics in the treatment of opioid dependence. Clinical Pharmacokinetics. 44(7):661–680.

EMEA (European Agency for the Evaluation of Medicinal Products). 2001. EMEA Public Statement on the Recommendation to Suspend Marketing Authorization for ORLAAM (levacetylmethadol) in the European Union. [Online]. Available: http://www.emea.eu.int/pdfs/human/press/pus/877601en.pdf [accessed June 30, 2006].

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

Enghusen Poulsen H, Loft S, Andersen JR, Andersen M. 1992. Disulfiram therapy—adverse drug reactions and interactions. Acta Psychiatrica Scandinavica Suppl. 369:59–65.

Faggiano F, Vigna-Taglianti F, Versino E, Lemma P. 2003. Methadone maintenance at different dosages for opioid dependence. The Cochrane Database of Systematic Reviews. (3):CD002208.

Fairbank JA, Dunteman GH, Condelli WS. 1993. Do methadone patients substitute other drugs for heroin? Predicting substance use at 1-year follow-up. American Journal of Drug and Alcohol Abuse. 19(4):465–474.

Frank B, Galea J. 1996. Cocaine trends and other drug trends in New York City, 1986-1994. Journal of Addictive Diseases. 15:1–12

Friedmann PD, Zhang Z, Hendrickson J, Stein MD, Gerstein DR. 2003. Effect of primary medical care on addiction and medical severity in substance abuse treatment programs. Journal of General Internal Medicine. 18:1–8.

Friedmann PD, Hendrickson JC, Gerstein DR, Zhang Z, Stein MD. 2006. Do mechanisms that link addiction treatment patients to primary care influence subsequent utilization of emergency and hospital care? Medical Care. 44(1):8–15.

Fudala PJ, Bridge TP, Herbert S, Williford WO, Chiang CN, Jones K, Collins J, Raisch D, Casadonte P, Goldsmith RJ, Ling W, Malkerneker U, McNicholas L, Renner J, Stine S, Tusel D; Buprenorphine/Naloxone Collaborative Study Group. 2003. Office-based treatment of opiate addiction with a sublingual-tablet formulation of buprenorphine and naloxone. New England Journal of Medicine. 349(10):949–958.

Fugelstad A, Rajs J, Bottiger M, de Verdier MG. 1995. Mortality among HIV-infected intravenous drug addicts in Stockholm in relation to methadone treatment. Addiction. 90:711–716.

Fugelstad A, Annell A, Rajs J, Agren G. 1997. Mortality and causes and manner of death among drug addicts in Stockholm during the period 1981–1992. Acta Psychiatrica Scandinavica. 96:169–175.

Fugelstad A, Agren G, Romelsjo A. 1998. Changes in mortality, arrests, and hospitalizations in nonvoluntarily treated heroin addicts in relation to methadone treatment. Substance Use & Misuse. 33(14):2803–2817.

George TP, Chawarski MC, Pakes JA, Carroll KM, Kosten TR, Schottenfeld RS. 2000. Disulfiram versus placebo for cocaine dependence in buprenorphine-maintained subjects: A preliminary trial. Biological Psychiatry. 47:1080–1086.

Gibson DR, McCusker J, Chesney M. 1998. Effectiveness of psychosocial interventions in preventing HIV risk behaviour in injecting drug users. AIDS. 12(8):919–929.

Gossop M, Marsden J, Steward D, Rolfe A. 2000. Patterns of improvement after methadone treatment: 1 year follow-up results from the National Treatment Outcome Research Study (NTORS). Drug Alcohol Dependency. 60:275–286.

Gouny P, Gaitz JP, Vayssairat M. 1999. Acute hand ischemia secondary to intra-arterial buprenorphine injection: Treatment with iloprost and dextran-40—a case report. Angiology. 50:605–606.

Gowing LR, Farrell M, Bornemann R, Ali R. 2004. Substitution treatment of injecting opioid users for prevention of HIV infection. The Cochrane Database of Systematic Reviews. (4):CD004145.

Gowing LR, Farrell M, Bornemann R, Sullivan LE, Ali RL. 2005. Brief report: Methadone treatment of injecting opioid users for prevention of HIV infection. Journal of General Internal Medicine. 20:1–3.

GRADE Working Group. 2004. Grading quality of evidence and strength of recommendation. British Medical Journal. 328:1490–1498.

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

Grella CE, Anglin MD, Wugalter SE. 1995. Cocaine and crack use and HIV risk behaviors among high-risk methadone maintenance clients. Drug and Alcohol Dependence. 37: 15–21.

Grella CE, Anglin MD, Annon JJ. 1996. HIV risk behaviors among women in methadone maintenance treatment. Substance Use and Misuse. 31(3):277–301.

Grella CE, Anglin MD, Wugalter SE. 1997. Patterns and predictors of cocaine and crack use by clients in standard and enhanced methadone maintenance treatment. American Journal of Drug and Alcohol Abuse. 23:15–42.

Guichard A, Lert F, Calderon C, Gaigi H, Maguet O, Soletti J, Brodeur JM, Richard L, Benigeri M, Zunzunegui MV. 2003. Illicit drug use and injection practices among drug users on methadone and buprenorphine maintenance treatment in France. Addiction. 98(11):1585–1597.

Gunne LM, Gronbladh L. 1981. The Swedish methadone maintenance program: A controlled study. Drug and Alcohol Dependence. 7(3):249–256.

Guo S, Jiang Z, Wu Y. 2001. Efficacy of naltrexone hydrochloride for preventing relapse among opiate-dependent patients after detoxification. Hong Kong Journal of Psychiatry. 11(4):2–8.

Gurel O, Carise D, Kendig C, McLellan AT. 2005. Developing CASPAR: A computer-assisted system for patient assessment and referral. Journal of Substance Abuse Treatment. (3):281–289.

Haisin DS, Grant BF, Endicott J, Hartford TC. 1988. Cocaine and heroin dependence compared in polydrug abusers. American Journal of Public Health. 8:567–569.

Harris RM, Bausell RB, Scott DE, Hetherington SE, Kavanagh KH. 1998. An intervention for changing high-risk HIV behaviors of African-American, drug dependent women. Research in Nursing and Health. 21:239–250.

Hartgers C, van den Hoek A, Krijnen P, Coutinho RA. 1992. HIV prevalence and risk behavior among injecting drug users who participate in “low-threshold” methadone programs in Amsterdam. American Journal of Public Health. 82(4):547–551.

Heinemann A, Iwersen-Bergmann S, Stein S, Schmoldt A, Puschel K. 2000. Methadone-related fatalities in Hamburg 1990–1999: Implications for quality standards in maintenance treatment? Forensic Science International. 113:449–455.

Higgins ST, Budney AJ, Bickel WK, Hughes JR, Foerg F, Fenwick W. 1991. A behavioral approach to achieving initial cocaine abstinence. American Journal of Psychiatry. 148:1218–1224.

Higgins ST, Budney AJ, Bickel WK, Hughes JR, Foerg F, Badger G. 1993. Achieving cocaine abstinence with a behavioral approach. American Journal of Psychiatry. 150:763–769.

Higgins ST, Budney AJ, Bickel WK, Foerg FE, Donham R, Badger GJ. 1994. Incentives improve outcome in outpatient behavioral treatment of cocaine dependence. Archives of General Psychiatry. 51:568–576.

Higgins ST, Wong CJ, Badger GJ, Ogden DE, Dantona RL. 2000. Contingent reinforcement increases cocaine abstinence during outpatient treatment and 1 year of follow-up. Journal of Consulting and Clinical Psychology. 68:64–72.

Higgins ST, Sigmon SC, Wong CJ, Heil SH, Badger GJ, Donham R, Dantona RL, Anthony S. 2003. Community reinforcement therapy for cocaine dependent outpatients. Archives of General Psychiatry. 60(10):1043–1052.

Hill AB. 1961. Principles of Medical Statistics. New York: Oxford University Press.

Hollister LE. 1978. Clinical evaluation of naltrexone treatment of opiate-dependent individuals. Report of the National Research Council Committee on Clinical Evaluation of Narcotic Antagonists. Archives of General Psychiatry. 35(3):335–340.

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

Hopwood M, Southgate E, Kippax S, Bammer G, Isaac-Toua G, MacDonald M. 2003. The injection of methadone syrup in New South Wales: Patterns of use and increased harm after partial banning of injecting equipment. Australian and New Zealand Journal of Public Health. 27:551–555.

Hser YI, Hoffman V, Grella CE, Anglin MD. 2001. A 33-year follow-up of narcotics addicts. Archives of General Psychiatry. 58(5):503–508.

Hubbard RL, Craddock SG, Anderson J. 2003. Overview of 5-year follow-up outcomes in the drug abuse treatment outcome studies (DATOS). Journal of Substance Abuse Treatment. 25:125–134.

IOM (Institute of Medicine). 1990. Treating Drug Problems: Volume 1. Washington, DC: National Academy Press.

IOM. 1995. Federal Regulation of Methadone Treatment. Washington, DC: National Academy Press.

IOM. 2005. Scaling Up Treatment for the Global AIDS Pandemic. Washington, DC: The National Academies Press.

Iribarne C, Berthou F, Carlhant D, Dreano Y, Picart D, Lohezic F, Riche C. 1998. Inhibition of methadone and buprenorphine N-dealkylations by three HIV-1 protease inhibitors. Drug Metabolism and Disposition. 26(3):257–260.

Johansson BA, Berglund M, Lindgren A. 2006. Efficacy of maintenance treatment with naltrexone for opioid dependence: A meta-analytical review. Addiction. 101:491–503.

Johnson RE, Eissenberg T, Stitzer ML, Strain EC, Liebson IA, Bigelow GE. 1995. A placebo controlled clinical trial of buprenorphine as a treatment for opioid dependence. Drug and Alcohol Dependence. 40(1):17–25.

Kakko J, Svanborg KD, Kreek MJ, Heilig M. 2003. 1-year retention and social function after buprenorphine-assisted relapse prevention treatment for heroin dependence in Sweden: A randomised, placebo-controlled trial. Lancet. 361(9358):662–668.

Katz EC, Chutuape MA, Jones HE, Stitzer ML. 2002. Voucher reinforcement for heroin and cocaine abstinence in an outpatient drug-free program. Experimental and Clinical Pharmacology. 10(2):136–143.

King VL, Kidorf MS, Stoller KB, Brooner RK. 2000. Influence of psychiatric comorbidity on HIV risk behaviors: Changes during drug abuse treatment. Journal of Addictive Diseases. 19:65–83.

Kintz P. 2001. Deaths involving buprenorphine: A compendium of French cases. Forensic Science International. 121:6–69.

Kirchmayer U, Davoli M, Verster A. 2003. Naltrexone maintenance treatment for opioid dependence. The Cochrane Database of Systematic Reviews. (2):CD001333.

Kosten TR, Rounsaville BJ, Kleber HD. 1987. A 2.5-year follow-up of cocaine use among treated opioid addicts. Have our treatments helped? Archives of General Psychiatry. 44:281–284.

Kosten TR, Rounsaville BJ, Kleber HD. 1988. Antecedents and consequences of cocaine abuse among opioid addicts. A 2.5-year follow-up. Journal of Nervous and Mental Disorders. 176(3):176–181.

Kosten TR, Krystal JH, Charney DS, Price LH, Morgan CH, Kleber HD. 1990. Opioid antagonist challenges in buprenorphine maintained patients. Drug and Alcohol Dependence 25(1):73–78.

Krook AL, Brors O, Dahlberg J, Grouff K, Magnus P, Roysamb E, Waal H. 2002. A placebo-controlled study of high dose buprenorphine in opiate dependents waiting for medication-assisted rehabilitation in Oslo, Norway. Addiction. 97(5):533–542.

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

Krupitsky EM, Zvartau EE, Masalov DV, Tsoi MV, Burakov AM, Egorova VY, Didenko TY, Romanova TN, Ivanova EB, Bespalov AY, Verbitskaya EV, Neznanov NG, Grinenko AY, O’Brien CP, Woody GE. 2004. Naltrexone for heroin dependence treatment in St. Petersburg, Russia. Journal of Substance Abuse Treatment. 26:285–294.

Krupitsky EM, Zvartau EE, Masalov DV, Tsoy MV, Burakov AM, Egorova VY, Didenko TY, Romanova TN, Ivanova EB, Bespalov AY, Verbitskaya EV, Neznanov NG, Grinenko AY, O’Brien CP, Woody GE. 2006. Naltrexone with or without fluoxetine for preventing relapse to heroin addiction in St. Petersburg, Russia. Journal of Substance Abuse Treatment. In press, corrected proof. [Available online July 24, 2006].

Kwiatkowski CF, Booth RE. 2001. Methadone maintenance as HIV risk reduction with street-recruited injecting drug users. Journal of Acquired Immune Deficiencies Syndromes. 26(5):483–489.

Ladewig D. 1990. Naltrexone—an effective aid in the psychosocial rehabilitation process of former opiate dependent patients. Therapeutische Umschau. 47(3):247–250.

Laine C, Hauck WW, Gourevitch, Rothman J, Cohen A, Turner BJ. 2001. Regular outpatient medical and drug abuse care and subsequent hospitalization of persons who use illicit drugs. Journal of the American Medical Association. 285(18):2355–2362.

Laine C, Lin YT, Hauck WW, Turner BJ. 2005. Availability of medical care services in drug treatment clinics associated with lower repeated emergency department use. Medical Care. 43(10):985–995.

Last J. 1995. A Dictionary of Epidemiology. 3rd edition. New York: Oxford University Press.

Leri F, Bruneau J, Stewart J. 2003. Understanding polydrug use: Review of heroin and cocaine co-use. Addiction. 98:7–22.

Lerner A, Sigal M, Bacalu A, Shiff R, Burganski I, Gelkopf M. 1992. A naltrexone double-blind placebo controlled study in Israel. Israel Journal of Psychiatry and Related Sciences. 29(1):36–43.

Lima MS, Reisser Lima AAP, Soares BGO, Farrell M. 2003. Antidepressants for cocaine dependence. The Cochrane Database of Systematic Reviews. (2):CD002950.

Lima Reisser A, Lima MS, Soares BGO, Farrell M. 2002. Carbamazepine for cocaine dependence. The Cochrane Database of Systematic Reviews. (2):CD002023.

Ling W, Charuvastra C, Collins JF, Batki S, Brown Jr. LS, Kintaudi P, Wesson DR, McNicholas L, Tusel DJ, Malkerneker U, Renner Jr. JA, Santos E, Casadonte P, Fye C, Stine S, Wang RIH, Segal D. 1998. Buprenorphine maintenance treatment of opiate dependence: A multicenter, randomized clinical trial. Addiction. 93(4):475–486.

Lintzeris N, Lenne M, Ritter A. 1999. Methadone injecting in Australia: A tale of two cities. Addiction. 94:1175–1178.

Lucas GM, Mullen BA, Weidle PJ, Hader S, MCaul ME, Moore RD. 2006. Directly administered antiretroviral therapy in methadone clinics is associated with improved HIV treatment outcomes, compared with outcomes among concurrent comparison groups. Clinical Infectious Diseases. 42:1628–1635.

MacCoun R, Reuter P. 2001. Drug War Heresies: Learning from Other Vices, Times, and Places. Cambridge, UK: Cambridge University Press.

Maddux JF, Desmond DP. 1997. Outcomes of methadone maintenance 1 year after admission. Journal of Drug Issues. 27(2):225–238.

Magura S, Siddiqi Q, Shapiro J, Grossman JI, Lipton DS, Marion IJ, Weisenfeld L, Amann KR, Koger J. 1991. Outcomes of an AIDS prevention program for methadone patients. International Journal of Addiction. 26(6):629–655.

Magura S, Kang SY, Nwakeze PC, Demsky S. 1998. Temporal patterns of heroin and cocaine use among methadone patients. Substance Use and Misuse. 33(12):2441–2467.

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

Margolin A, Avants SK, Warburton LA, Hawkins KA, Shi J. 2003. A randomized clinical trial of a manual-guided risk reduction intervention for HIV-positive injection drug users. Health Psychology. 22(2):223–228.

Mattick RP, Breen C, Kimber J, Davoli M. 2003a. Methadone maintenance therapy versus no opioid replacement therapy for opioid dependence. The Cochrane Database of Systematic Reviews. (2):CD002209.

Mattick RP, Kimber J, Davoli M. 2003b. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. The Cochrane Database of Systematic Reviews. (2):CD002207.

Maude-Griffin PM, Hohenstein JM, Humfleet GL, Reilly PM, Tusel DJ, Hall SM. 1998. Superior efficacy of cognitive-behavioral therapy for crack cocaine abusers: Main and matching effects. Journal of Consulting and Clinical Psychology. 66:832–837.

Mayet S, Farrell M, Ferri M, Amato L, Davoli M. 2004. Psychosocial treatment for opiate abuse and dependence. The Cochrane Database of Systematic Reviews. (4):CD004330.

McCance-Katz EF, Rainey PM, Friedland G, Kosten TR, Jatlow P. 2001. Effect of opioid dependence pharmacotherapies on zidovudine disposition. American Journal of Addictions. 10(4):296–307.

McCance-Katz EF, Rainey PM, Friedland G, Jatlow P. 2003. The protease inhibitor lopinavirritonavir may produce opiate withdrawal in methadone-maintained patients. Clinical Infectious Diseases. 37(4):476–482.

McCance-Katz EF, Rainey PM, Smith P, Morse GD, Friedland G, Boyarsky B, Gourevitch M, Jatlow P. 2006. Drug interactions between opioids and antiretroviral medications: Interaction between methadone, LAAM, and delavirdine. American Journal on Addictions. 15(1):23–34.

McGlothin WH, Anglin MD. 1981. Shutting off methadone: costs and benefits. Archives of General Psychiatry. 38:885–892.

McKay JR, Alterman AI, Cacciola JS, Rutherford MJ, O’Brien CP, Koppenhaver J. 1997. Group counseling versus individualized relapse prevention aftercare following intensive outpatient treatment for cocaine dependence. Journal of Consulting and Clinical Psychology. 65:778–788.

McLellan AT, Arndt IO, Metzger DS, Woody GE, O’Brien CP. 1993. The effects of psychosocial services in substance abuse treatment. Journal of the American Medical Association. 269(15):1953–1959.

Meandzija B, O’Connor PG, Fitzgerald B, Rounsaville BJ, Kosten TR. 1994. HIV infection and cocaine use in methadone maintained and untreated intravenous drug users. Drug and Alcohol Dependence. 36:109–113.

Mendelson J, Jones RT, Welm S, Baggott M, Fernandez I, Melby AK, Nath RP. 1999. Buprenorphine and naloxone combinations: The effects of three dose ratios in morphine-stabilized, opiate-dependent volunteers. Psychopharmacology. 141(1):37–46.

Metzger DS, Woody GE, McLellan AT, O’Brien CP, Druley P, Navaline H, DePhilippis D, Stolley P, Abrutyn E. 1993. Human immunodeficiency virus seroconversion among intravenous drug users in- and out-of-treatment: An 18-month prospective follow-up. Journal of Acquired Immune Deficiency Syndromes. 6(9):1049–1056.

Miller WR, Rollnick S. 1992. Motivational Interviewing: Preparing People to Change Addictive Behavior. New York: Guilford Press.

Minozzi S, Amato L, Vecchi S, Davoi M, Kirchmayer U, Verster A. 2006. Oral naltrexone maintenance treatment for opioid dependence. The Cochrane Database of Systematic Reviews. (1):CD001333.

Moatti JP, Carrieri MP, Spire B, Gastaut JA, Cassuto JP, Moreau J, Manif 2000 study group. 2000. Adherence to HAART in French HIV-infected injecting drugs users: The contribution of buprenorphine drug maintenance treatment. AIDS. 14(2):151–155.

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

Monti PM, Rohsenow DJ, Michalec E, Martin RA, Abrams DB. 1997. Brief coping skills treatment for cocaine abuse: Substance abuse outcomes at three months. Addiction. 92:1717–1728.

Moss AR, Vranizan K, Gorter R, Bacchetti P, Watters J, Osmond D. 1994. HIV seroconversion in intravenous drug users in San Francisco, 1985–1990. AIDS. 8(2):223–231.

Newman RG, Whitehill WB. 1979. Double-blind comparison of methadone and placebo maintenance treatments of narcotic addicts in Hong Kong. Lancet. 2(8141):485–488.

Nich C, Carroll KM. 2002. “Intention-to-treat” meets “missing data”: Implications of alternate strategies for analyzing clinical trials data. Drug and Alcohol Dependence. 68: 121–130.

Obadia Y, Perrin V, Feroni I, Vlahov D, Moatti JP . 2001. Injecting misuse of buprenorphine among French drug users. Addiction. 96(2):267–272.

O’Brien C, Kampman K. 2004. Opioids: Antagonists and partial agonists. In: The American Psychiatric Association Textbook of Substance Abuse Treatment. 3rd edition. Washington, DC: American Psychiatric Press, Inc. Pp. 305–319.

O’Farrell TJ, Fals-Stewart W. 2002. Behavioral couples and family therapy for substance abusers. Current Psychiatry Reports. 4(5):371–376.

O’Malley SS, Jaffe AJ, Chang G, Rode S, Schottenfeld R, Meyer RE, Rounsaville B. 1996. Six month follow-up of naltrexone and psychotherapy for alcohol dependence. Archives of General Psychiatry. 53:217–224.

Peirce JM, Petry NM, Stitzer ML, Blaine J, Kellogg S, Satterfield F, Schwartz M, Krasnansky J, Pencer E, Silva-Vazquez L, Kirby KC, Royer-Malvestuto C, Roll JM, Cohen A, Copersino ML, Kolodner K, Li R. 2006. Effects of lower-cost incentives on stimulant abstinence in methadone maintenance treatment: A national drug abuse treatment clinical trials network study. Archives of General Psychiatry. 63(2):201–208.

Petrakis IL, Carroll KM, Gordon LT, Nich C, McCance-Katz E, Rounsaville BJ. 2000. Disulfiram treatment for cocaine dependence in methadone-maintained opioid addicts. Addiction. 95:219–228.

Petry NM, Martin B. 2002. Low-cost contingency management for treating cocaine- and opioid-abusing methadone patients. Journal of Consulting and Clinical Psychology. 70:398–405.

Petry NM, Tedford J, Austin M, Nich C, Carroll KM, Rounsaville BJ. 2004. Prize reinforcement contingency management for treating cocaine users: How low can we go, and with whom? Addiction. 99:349–360.

Piotrowski NA, Tusel DJ, Sees KL, Reilly PM, Banys P, Meek P, Hall SM. 1999. Contingency contracting with monetary reinforcers for abstinence from multiple drugs in a methadone program. Experimental and Clinical Psychopharmacology. 7(4):399–411.

Prendergast ML, Urada D, Podus D. 2001. Meta-analysis of HIV risk reduction interventions with drug abuse treatment programs. Journal of Consulting and Clinical Psychology. 69(3):389–405.

Project MATCH Research Group. 1998. Matching alcoholism treatments to patient heterogeneity: Treatment main effects and matching effects on drinking during treatment. Journal of Studies on Alcohol. 59:631–639.

Rawson RA, Glazer M, Callahan EJ, Liberman RP. 1979. Naltrexone and behaviour therapy for heroin addiction. NIDA Research Monograph Series. 25:26–43.

Rawson RA, Gonzales R, Brethen P. 2002. Treatment of methamphetamine use disorders: An update. Journal of Substance Abuse Treatment. 23:145–150.

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

Rawson RA, Marinelli-Casey P, Anglin MD, Dickow A, Frazier Y, Gallagher C, Galloway GP, Herrell J, Huber A, MacCann MJ, Obert J, Pennell S, Reiber C, Vandersloot D, Zweben J; Methamphetamine Treatment Project Corporate Authors. 2004. A multi-site comparison of psychosocial approaches for the treatment of methamphetamine dependence. Addiction. 99:708–717.

Reid G, Kamarulzaman, Sran SK. 2005. Rapid Situational Assessment of Malaysia. [Online]. Available: http://chr.asn.au/freestyler/gui/files//Rapid%20Situation%20Assessment%20of%20Malaysia1.pdf [accessed June 28, 2006].

Reynaud M, Petit G, Potard D, Couty P. 1998. Six deaths linked to concomitant use of buprenorphine and benzodiazepines. Addiction. 93:1385–1392.

Ritter A, Di Natale R. 2005. The relationship between take-away methadone policies and methadone diversion. Drug and Alcohol Review. 24:347–352.

Rohsenow DJ, Monti PM, Martin RA, Colby SM, Myers MG, Gulliver SB, Brown RA, Mueller TI, Gordon A, Abrams DB. 2004. Motivational enhancement and coping skills training for cocaine abusers: Effects on substance use outcomes. Addiction. 99(7): 862–874.

Rooney S, Kelly G, Bamford L, Sloan D, O’Connor JJ. 1999. Co-abuse of opiates and benzodiazepines. Irish Journal of Medical Science. 168(1):36–41.

Roozen HG, Boulogne JJ, van Tulder MW, van den Brink W, De Jong CAJ, Kerkhof AJFM. 2004. A systematic review of the effectiveness of the community reinforcement approach in alcohol, cocaine and opioid addiction. Drug and Alcohol Dependence. 74:1–13.

Rothbard A, Alterman A, Rutherford M, Liu F, Zelinski S, McKay J. 1999. Revisiting the effectiveness of methadone treatment on crime reductions in the 1990s. Journal of Substance Abuse Treatment. 16(4):329–335.

Roxanne Laboratories, Inc. 2003. Product Discontinuation Notice. ORLAAM ® (Levomethadyl hydrochloride acetate) Oral Solution, 10 mg/mL, CII. [Online]. Available: http://www.fda.gov/cder/drug/shortages/orlaam.htm [accessed August 28, 2006].

Samet JH, Friedmann P, Saitz R. 2001. Benefits of linking primary medical care and substance abuse services: Patient, provider, and societal perspectives. Archives of Internal Medicine. 161:85–91.

San L, Pomarol G, Peri JM, Olle JM, Cami J. 1991. Follow-up after a six-month maintenance period on naltrexone versus placebo in heroin addicts. British Journal of Addiction. 86(8):983–990.

Schilling RF, El-Bassel N, Schinke SP, Gordon K, Nichols S. 1991. Building skills of recovering women drug users to reduce heterosexual AIDS transmission. Public Health Reports. 106:297–304.

Schottenfeld RS. 2004. Opioids: Maintenance treatment. The American Psychiatric Publishing Textbook of Substance Abuse Treatment. 3rd edition. Galanter M, Kleber H, eds. Washington, DC: American Psychiatric Publishing, Inc.

Schottenfeld RS, Pakes J, Ziedonis D, Kosten TR. 1993. Buprenorphine: Dose-related effects on cocaine and opioid use in cocaine-abusing opioid-dependent humans. Biological Psychiatry. 34(1–2):66–74.

Schottenfeld RS, Pakes J, Oliveto A, Ziedonis D, Kosten TR. 1997. Buprenorphine vs methadone maintenance treatment for concurrent opioid dependence and cocaine abuse. Archives of General Psychiatry. 54:713–720.

Schottenfeld RS, Chawarski MC, Pakes JR, Pantalon MV, Carroll KM, Kosten TR. 2005. Methadone versus buprenorphine with contingency management or performance feedback for cocaine and opioid dependence. American Journal of Psychiatry. 162(2): 340–349.

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

Schutz CG, Vlahov D, Anthony JC, Graham NM. 1994. Comparison of self-reported injection frequencies for past 30 days and 6 months among intravenous drug users. Journal of Clinical Epidemiology. 47:191–195.

Schwartz RP, Highfield DA, Jaffe JH, Brady JV, Butler CB, Rouse CO, Callaman JM, O’Grady KE, Battjes RJ. 2006. A randomized controlled trial of interim methadone maintenance. Archives of General Psychiatry. 63(1):102–109.

Scorzelli JF. 1992. Has Malaysia’s antidrug effort been effective. Journal of Substance Abuse Treatment. 9(2):171–176.

Secades-Villa R, Fernande-Hermida JR, Arnaez-Montaraz C. 2004. Motivational interviewing and treatment retention among drug user patients: A pilot study. Substance Use and Misuse. 39(9):1369–1378.

Sees KL, Delucchi KL, Masson C, Rosen A, Clark HW, Robillard H, Banys P, Hall SM. 2000. Methadone maintenance vs 180-day psychosocially enriched detoxification for treatment of opioid dependence: A randomized controlled trial. Journal of the American Medical Association. 283(10):1303–1310.

Sellman JD, Sullivan PF, Dore GM, Adamson SJ, MacEwan I. 2001. A randomized controlled trial of Motivational Enhancement Therapy (MET) for mild to moderate alcohol dependence. Journal of Studies on Alcohol. 62:389–396.

Serpellini G, Carrieri MP. 1994. Methadone treatment as a determinant of HIV risk reduction among injecting drug users: A nested case-control study. AIDS Care. 6(2):215–220.

Shoptaw S, Reback CJ, Peck JA, Yang X, Rotheram-Fuller E, Larkins S, Veniegas RC, Freese TE, Hucks-Ortiz C. 2005. Behavioral treatment approaches for methamphetamine dependence and HIV-related sexual risk behaviors among urban gay and bisexual men. Drug and Alcohol Dependence. 78:125–134.

Shoptaw S, Huber A, Peck J, Yang X, Liu J, Dang J, Roll J, Shapiro B, Rotheram-Fuller E, Ling W. 2006. Randomized, placebo-controlled trial of sertraline and contingency management for the treatment of methamphetamine dependence. Drug and Alcohol Dependence. 85(1):12–18.

Shufman EN, Porat S, Witzum E, Gandacu C, Bar-Hamburger R, Ginath Y. 1994. The efficacy of naltrexone in preventing reabuse of heroin after detoxification. Biological Psychiatry. 35(12):935–945.

Simpson DD, Joe GW, Rowan-Szal G, Greener J. 1995. Client engagement and change during drug abuse treatment. Journal of Substance Abuse. 7:117–134.

Soares BGO, Lima MS, Lima Reisser A, Farrell M. 2003. Dopamine agonists for cocaine dependence. The Cochrane Database of Systematic Reviews. (2):CD003352.

Sorenson JL, Copeland AL. 2000. Drug abuse treatment as an HIV prevention strategy: A review. Drug and Alcohol Dependence. 59:17–31.

Sorensen JL, London J, Heitzmann C, Gibson DR, Morales E, Dumontet R, Acree M. 1994. Psychoeducational group approach: HIV risk reduction in drug users. AIDS Education and Prevention. 6:95–112.

Srisurapanont M, Jarusuraisin N, Kittirattanapaiboon P. 2001. Treatment for amphetamine dependence and abuse. The Cochrane Database of Systematic Reviews. (4):CD003022.

Stark K, Muller R, Bienzle U, Guggenmoos-Holzmann I. 1996. Methadone maintenance treatment and HIV risk-taking behaviour among injecting drug users in Berlin. Journal of Epidemiology and Community Health. 50:534–537.

Stotts AL, Schmitz JM, Rhoades HM, Grabowski J. 2001. Motivational interviewing with cocaine-dependent patients: A pilot study. Journal of Consulting and Clinical Psychology. 69(5):858–862.

Strain EC, Stitzer ML, Liebson IA, Bigelow GE. 1993. Dose-response effects of methadone in the treatment of opioid dependence. Annals of Internal Medicine. 119:23–27.

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×

Strain EC, Bigelow GE, Liebson IA, Stitzer ML. 1999. Moderate- vs high-done methadone in the treatment of opioid dependence: A randomized trial. Journal of the American Medical Association. 281(11):1000–1005.

Strang J, Marsden J, Cummins M, Farrell M, Finch E, Gossop M, Stewart D, Welch S. 2000. Randomized trial of supervised injectable versus oral methadone maintenance: Report of feasibility and 6-month outcome. Addiction. 95(11):1631–1645.

Strang J, McCambridge J, Best D, Beswick T, Bearn J, Rees S, Gossop M. 2003. Loss of tolerance and overdose mortality after inpatient opiate detoxification: Follow up study. British Medical Journal. 326:959–960.

Suh JJ, Pettinati HM, Kampman KM, O’Brien CP. 2006. The status of Disulfiram: A half century later. Journal of Clinical Psychopharmacology. 26(3):290–302.

Tennant FS, Rawson RA, Cohen AJ, Mann A. 1984. Clinical experience with naltrexone in suburban opioid addicts. Journal of Clinical Psychiatry. 45(9 pt 2):42–45.

Termorshuizen F, Krol A, Prins M, Geskus R, van den Brink W, van Ameijden EJ. 2005. Prediction of relapse to frequent heroin use and the role of methadone prescription: An analysis of the Amsterdam Cohort Study among drug users. Drug and Alcohol Dependence. 79(2):231–240.

Thiede H, Hagan H, Murrill CS. 2000. Methadone treatment and HIV and hepatitis B and C risk reduction among injectors in the Seattle area. Journal of Urban Health. 77(3): 331–345.

Turner BJ, Laine C, Yang CP, Hauck WW. 2003. Effects of long-term, medically supervised, drug-free treatment and methadone maintenance treatment on drug users’ emergency department use and hospitalization. Clinical Infectious Diseases. 37(Suppl 5):S457.

U.S. FDA (Food and Drug Administration). 2001, March. Index of Safety-Related Drug Labeling Changes Summaries Approved by the FDA Center for Drug Evaluation and Research (CDER). Medwatch. [Online]. Available: http://www.fda.gov/medwatch/safety/2001/mar01.htm [accessed June 30, 2006].

van Ameijden EJ, Langendam MW, Coutinho RA. 1999. Dose-effect relationship between overdose mortality and prescribed methadone dosage in low-threshold maintenance programs. Addictive Behaviors. 24(4):559–563.

Vanichseni S, Wongsuwan B, Choopanya K, Wongpanich K. 1991. A controlled trial of methadone maintenance in a population of intravenous drug users in Bangkok: Implications for prevention of HIV. International Journal of Addictions. 26(12):1313–1320.

Varescon I, Vidal-Trecan G, Nabet N, Boissonnas A. 2002. Buprenorphine abuse: High dose intravenous administration of buprenorphine. L’Encéphale. 5(Pt 1):397–402.

Vocci FJ, Elkashef A. 2005. Pharmacotherapy and other treatments for cocaine abuse and dependence. Current Opinion in Psychiatry. 18:265–270.

Washton AM, Pottash AC, Gold MS. 1984. Naltrexone in addicted business executives and physicians. Journal of Clinical Psychiatry. 45(9 pt 2):39–41.

WHO (World Health Organization), United Nations Office on Drugs and Crime, and Joint United Nations Programme on HIV/AIDS. 2004. Substitution Maintenance Therapy in the Management of Opioid Dependence and HIV/AIDS Prevention: Position Paper. Geneva, Switzerland: WHO.

Williams AB, McNelly EA, Williams AE, D’Aquila RT. 1992. Methadone maintenance treatment and HIV type 1 seroconversion among injecting drug users. AIDS Care. 4(1): 35–41.

Williamson PA, Foreman KJ, White JM, Anderson G. 1997. Methadone-related overdose deaths in South Australia 1984–1994. Medical Journal of Australia. 166: 302–305.

Yancovitz SR, Des Jarlais DC, Peyser NP, Drew E, Friedmann P, Trigg HL, Robinson JW. 1991. A randomized trial of an interim methadone maintenance clinic. American Journal of Public Health. 81(9):1185–1191.

Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 74
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 75
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 76
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 77
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 78
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 79
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 80
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 81
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 82
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 83
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 84
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 85
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 86
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 87
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 88
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 89
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 90
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 91
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 92
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 93
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 94
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 95
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 96
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 97
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 98
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 99
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 100
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 101
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 102
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 103
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 104
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 105
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 106
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 107
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 108
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 109
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 110
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 111
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 112
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 113
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 114
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 115
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 116
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 117
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 118
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 119
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 120
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 121
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 122
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 123
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 124
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 125
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 126
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 127
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 128
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 129
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 130
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 131
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 132
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 133
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 134
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 135
Suggested Citation:"2 Treatment for Drug Dependence." Institute of Medicine. 2007. Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence. Washington, DC: The National Academies Press. doi: 10.17226/11731.
×
Page 136
Next: 3 Sterile Needle and Syringe Access and Outreach and Education »
Preventing HIV Infection Among Injecting Drug Users in High-Risk Countries: An Assessment of the Evidence Get This Book
×
Buy Paperback | $83.00 Buy Ebook | $64.99
MyNAP members save 10% online.
Login or Register to save!
Download Free PDF

Drug dependence is a complex, chronic, relapsing condition that is often accompanied by severe health, psychological, economic, legal, and social consequences. Injecting drug users are particularly vulnerable to HIV and other bloodborne infections (such as hepatitis C) as a result of sharing contaminated injecting equipment. All drug-dependent individuals, including injecting drug users (IDUs), may be at increased risk of HIV infection because of high-risk sexual behaviors. There are an estimated 13.2 million injecting drug users (IDUs) world-wide—78 percent of whom live in developing or transitional countries. The sharing of contaminated injecting equipment has become a major driving force of the global AIDS epidemic and is the primary mode of HIV transmission in many countries. In some cases, epidemics initially fueled by the sharing of contaminated injecting equipment are spreading through sexual transmission from IDUs to non-injecting populations, and through perinatal transmission to newborns. Reversing the rise of HIV infections among IDUs has thus become an urgent global public health challenge—one that remains largely unmet.

In response to this challenge, the Institute of Medicine convened a public workshop in Geneva in December 2005 to gather information from experts on IDU-driven HIV epidemics in the most affected regions of the world with an emphasis on countries throughout Eastern Europe, the Commonwealth of Independent States, and significant parts of Asia. Experts from other regions also provided information on their experiences in preventing HIV infection among IDUs. This report provides a summary of the workshop discussions.

Preventing HIV Infection among Injecting Drug Users in High Risk Countries describes the evidence on the intermediate outcomes of drug-related risk and sex-related risk prior to examining the impact on HIV transmission. This report focuses on programs that are designed to prevent the transmission of HIV among injecting drug users. These programs range from efforts to curtail non-medical drug use to those that encourage reduction in high-risk behavior among drug users. Although the report focuses on HIV prevention for IDUs in high-risk countries, the Committee considered evidence from countries around the world. The findings and recommendations of this report are also applicable to countries where injecting drug use is not the primary driver, but in which injection drug use is nevertheless associated with significant HIV transmission.

  1. ×

    Welcome to OpenBook!

    You're looking at OpenBook, NAP.edu's online reading room since 1999. Based on feedback from you, our users, we've made some improvements that make it easier than ever to read thousands of publications on our website.

    Do you want to take a quick tour of the OpenBook's features?

    No Thanks Take a Tour »
  2. ×

    Show this book's table of contents, where you can jump to any chapter by name.

    « Back Next »
  3. ×

    ...or use these buttons to go back to the previous chapter or skip to the next one.

    « Back Next »
  4. ×

    Jump up to the previous page or down to the next one. Also, you can type in a page number and press Enter to go directly to that page in the book.

    « Back Next »
  5. ×

    Switch between the Original Pages, where you can read the report as it appeared in print, and Text Pages for the web version, where you can highlight and search the text.

    « Back Next »
  6. ×

    To search the entire text of this book, type in your search term here and press Enter.

    « Back Next »
  7. ×

    Share a link to this book page on your preferred social network or via email.

    « Back Next »
  8. ×

    View our suggested citation for this chapter.

    « Back Next »
  9. ×

    Ready to take your reading offline? Click here to buy this book in print or download it as a free PDF, if available.

    « Back Next »
Stay Connected!