Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter.
Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.
Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.
OCR for page 26
1
Introduction
Drug addiction' is a highly complex process that involves physiological,
behavioral, psychological, and social components. Similarly, its treatment usually
takes a multifaceted approach. Methods of treating drug addiction include
pharmacotherapy (the use of medications), psychotherapy (group and individual
counseling) and social support (such as in the form of employment opportunities
and education).
Pharmacotherapy has not received broad support from the federal govern-
ment, nor has the private sector been active in developing anti-addiction
medications. There are many reasons for the apparent lack of support of and
activity in this kind of drug development. Clearly, the absence of a large, vocal
advocacy group that would voice strong support and lobby for treatment funding
and research contributes to the lack of federal leadership and the dearth of anti-
addiction medications. But, it should be recognized that drug addiction is a
disease thriller, l991:one that is widespread in the United States (there are an
estimated 0.5-l million heroin-dependent individuals and 2.1 million cocaine-
dependent individuals) and shows no signs of abating according to national
surveys (Hunt and Rhodes, 1992; Kreek, 1992; Johnston et al., 1994a,b~and
like people with any other medical condition, drug addicted individuals deserve
to be considered as candidates for medications.
'Drug addiction is defined as the compulsive use of a drug despite adverse
consequences. This report focuses on opiate and cocaine addictions and does not address
alcohol and nicotine addictions.
26
OCR for page 27
INTRODUCTION
27
In 1990, the Medications Development Division (MDD) of the National
Institute on Drug Abuse (NIDA) was established to support research and
development and to work with the private sector to secure Food and Drug
Administration (FDA) marketing approval for new medications to treat drug
addiction (see mission statement in Appendix B).
This report of the Institute of Medicine (IOM) Committee to Study
Medication Development and Research at the National institute on Drug Anuse
focuses on pharmacotherapy for the treatment of drug addiction for several
reasons:
· Phannacotherapy for opiate addiction is successful, and it seems
reasonable to assume that effective medications could be useful in treating
cocaine addiction.
.
Pharmacotherapies will expand the range of treatment options
available to physicians and treatment programs (U.S. Congress, Senate,
1989).
.
· Pharmacotherapies might enhance other treatment modalities.
Pharmacotherapy might permit more cost-effective outpatient
approaches.
Additionally, Congress has specifically required the committee to determine the
current conditions for developing anti-addiction medications. The need for
pharmacotherapy is further driven by the public-health, economic, and criminal
repercussions of illicit drug use (particularly use of opiates and cocaine). The
committee focused its attention on medications to treat opiate and cocaine
addictions, although it recognizes that the two addictive drugs that are most
important with respect to morbidity, mortality, and economic costs are alcohol
and nicotine.
This chapter examines the magnitude of the illicit drug-use problem and its
effects on society. Chapter 2 examines the state of scientific knowledge
concerning the mechanisms of drub addiction and the difficulty of developing
A, ., . _
anti-addiction medications. the work of NIDA's MDD is discussed in Chapter
3. Chapters 4-9 focus on the disincentives faced by the pharmaceutical industry
in developing anti-addiction medications-treatment financing, physician training
and education, federal and state regulation, and market issues- and present policy
and legislative solutions.
PUBLIC-HEALTH REPERCUSSIONS OF ILLICIT DRUG USE
Drug addiction has both individual and societal ramifications. Overall
societal trends in drug-addiction policy have ranged from minimal libertarian
OCR for page 28
28
DEVELOPMENT OF MEDICATIONS
approaches in the middle 1800s to medical and criminal approaches that have
alternated in emphasis since the late 1800s (IOM, 1990~. Current government
approaches are both medical and criminal, involving federal expenditures for
drug enforcement and interdiction and federal, state, and private expenditures for
drug treatment and drug-addiction research (IOM, 1990~.
Historical analysis has demonstrated that policy trends are driven by various
factors, including the social class of drug-users, prevailing perceptions regarding
the causes of drug addiction (e.g., personal choice, physiological dependence,
moral weakness, and genetic predisposition), the limited availability of effective
treatments (e.g., methadone), and the relation of the costs of drug-related
violence to the Fublic-health costs of drug addiction. Increasingly violence itself
is being viewed as a public-health problem as evidenced by increasing public
support of antiviolence initiatives in the agencies of the Department of Health
and Human Services (DHHS), such as the Centers for Disease Control and
Prevention (CDC). This shin coincides with a well-defined relationship between
drug addiction and the acquired immune deficiency syndrome (AIDS) epidemic;
mounting data on the role of drug addiction in the alarming rise of tuberculosis
(TB), particularly the often intractable and deadly drug-resistant form; and the
increase in the number of drug-exposed infants. Thus, the development of anti-
addiction medications to treat illicit drug use has ramifications not only for
addicted individuals, but also for society at large.
Health Consequences: Violence
Violence is now accepted as one of the major public-health problems facing
the United States2, and the CDC has given the prevention of violence one of its
highest priorities (Koop and Lundberg, 1992; Rosenberg et al., 1992; Schneider
et al., 1992~. Violence and illicit drug use are inextricably linked through several
scenarios: the "turf battles" of drug sale and drug distribution, the criminal and
open violent behavior prompted by the need for money to support drug use, and
the violence (often domestic) associated with the pharmacological effects of some
drugs on the drug-addicted individual (BJS, 1992; Marwick, 1992~. In the illegal
drug business, violence is systemic and is the typical interaction used to protect
and expand markets and deal with competitors, with buyers or sellers suspected
of cheating, and with police or witnesses (BJS, 19921.
2Violence has many causes, including the direct behavioral disinhibiting effects of
alcohol. Of state prison inmates surveyed who were convicted of committing homicide,
25 percent reported being under the influence of alcohol at the time of the offense (BJS,
1993~.
OCR for page 29
INTRODUCTION
29
In the circular nature of the drug-crime relationship, persons with criminal
records are more likely than persons without criminal records to report being
drug-users, and drug-users report greater involvement with crime (BJS, 1992~.
In a 1991 survey of state-prison inmates, 28 percent of inmates incarcerated for
violent crimes reported committing the crimes while under the influence of
drugs, and 27 percent reported committing robbery to obtain money to buy drugs
(BJS, 1993~. Data from the 1991 Drug Use Forecasting Program (a 24-city
program involving interviews and urine-tests of a sample of arrested persons)
indicate that 65 percent of males arrested for robbery and 48 percent of males
arrested for homicide had evidence of illicit drug use in their urine (NIJ, 1992~.
Data on arrested females show even higher percentages 76 percent arrested for
robbery, 50 percent arrested for assault, and 65 percent arrested for homicide had
evidence of illicit drug use in their urine (NIJ, 1992~. Cocaine was the most
prevalent drug, with percentages as high as 62 percent of arrested males in
Manhattan and Philadelphia (NIJ, 1992~. Violence and drug use are also
connected through drugs' pharmacological activity-especially that of such
stimulants as cocaine, crack cocaine, phencyclidine (PCP), and ampheta-
mines-which can produce irritability, paranoia, and a"need for action" that
increases the likelihood of violence (Miller et al., 1991; BJS, 1992; Marwick,
1992~. The links between violence and drug addiction add to the seriousness of
the public-health need for effective treatment of drug addiction.
Health Consequences: AIDS
Injection of illicit drugs is the second most common risk behavior associated
with the spread of AIDS, and in some sections of the U.S. recent data show that
heterosexual drug users account for the largest group of new AIDS cases (CDC,
1994; Goldstein, 1994~. More than one-third (37 percent) of AIDS cases reported
from June 1993 through June 1994 were related to injection of illicit drugs
through the sharing of contaminated injection equipment, through heterosexual
contact with an injecting drug-user (IDU), or through maternal injection of drugs
(Table 1.1) (CDC, 1994~. In women, the percentages of AIDS cases involving
injection of illicit drugs are alarmingly high. Of the 51,235 female AIDS cases
reported to CDC through June 1994 almost half (24,660 cases) were attributable
to injection of illicit drugs and another 19 percent (9,976 cases) to sex with
infected IDU partners (CDC, 1994~. The current prevalence of the human
immunodeficiency virus (HIV) in the estimated 1.1-1.8 million IDUs is unknown
(OTA, 1990~. However, of those in treatment programs, an estimated
61,000-398,000 IDUs are infected with HIV; the estimates vary in different
regions of the United States and reach a high of 65 percent in New York City
(OTA, 1990; Hahn et al., 1989~.
OCR for page 30
30
DEVELOPMENT OF MEDICATIONS
TABLE 1.1 AIDS Cases Related to Injection of Illicit Drugs (Percentage of total cases)
Exposure Category Cases Reported Cumulative Total
June 1993-June 1994 Reported
Injecting drug use:
Men
Women
Heterosexual contact with an
injecting drug user:
17,441 (20.5)
6,138 (7)
73,705 (18.3)
24,660 (6)
Men959 (1) 4,263 (1)
Women2,197 (3) 9,976 (2.5)
Men who have sex with men
and inject drugs4,165 (5) 25,447 (6)
Pediatric cases (<13 years old):
Mother who is an injecting
drug user
Mother who has sex with
an injecting drug user
Total cases related to injecting
drug use
284 (0.3)2,192 (0.5)
1 37 (0.2)969 (0.2)
3 1,321 (37)141,212 (35)
Total cases reported 85,260 401,749
SOURCE: CDC, 1994.
AIDS and illicit drug use are linked not only by injection drug use, but also
through an increase in high-risk sexual behaviors and perinatal transmission of
HIV. Such behaviors include exchange of sex for drugs, unprotected sex and
multiple partners, and prostitution to gain money to buy drugs (Turner et al.,
1989~. Heroin and cocaine alone or in combination are the most common
injectable drugs, although some injection of amphetamines has also been reported
(OTA, 1990~. Of the 5,734 cases of AIDS in children under 13 years old
reported to CDC through June 1994,89 percent are attributable to perinatal HIV
transmission (CDC, 1994~. Most (55 percent) of the pediatric AIDS cases are
associated with injection of illicit drugs 38 percent with maternal injection of
drugs and 17 percent with maternal sexual contact with an IDU (CDC, 1994~.A11
infants bone to HIV-infected mothers carry passively acquired maternal
antibodies that make them HIV-seropositive, and an estimated 25-35 percent of
these infants are actually infected (Hardy, 1991~.
OCR for page 31
INTRODUCTION
31
Health Consequences: Tuberculosis
TB was once a major public-health problem in the United States that caused
many deaths, but it declined with the discovery of effective medications and with
increased public-health screening and intervention programs. TB is an infectious
bacterial disease that commonly affects the lungs (pulmonary type) but can also
affect other organ systems (systemic type). It is again an immediate threat to the
well-being of thousands of Americans who are homeless, live in poverty, take
illicit drugs, or are infected with HIV. The very factors that are contributing
most greatly to the increase in TB also present severe challenges to stemming its
further spread (OTA, 1993~. For example, CDC recently reported that nearly 23
percent of inmates in correctional facilities had positive skin tests for TB (CDC,
1993 a). The closed nature of the prison environment, coupled with overcrowding,
makes prisons ideal for transmission of TB. Prisons also have a high concentra-
tion of people from environments of poverty, and the inmate population has a
high prevalence of drug addiction. Most inmates will re-enter the community,
and failures of the prison health system will have impacts outside the prison
walls.
The emergence of TB strains that are resistant to many of the standard
medications exacerbates the threat. From 1985 to 1992, rates of TB increased
significantly in people 25~4 years old (54.5 percent increase), Hispanics (74.5
percent increase), and African-Americans (26.8 percent increase) (CDC, 1993b).
TB has also increased greatly in children, presumably in part through transmis-
sion from older family members (CDC, 1993b). Drug-resistant TB is high among
IDUs and those infected with HIV. Positive skin tests for TB have been found
in nearly 10 percent of patients in drug-treatment programs (CDC, 1993a). The
incidence of TB among those with HIV is almost 500 times that in the non-HIV-
infected population (Barnes et al., 1991~. That is an ominous figure because
people in the later, more severe stages of AIDS often do not test positive for TB
in standard skin tests, even if they have active TB (Barnes et al., 1 99 1; Braun et
al., 1993~; thus, simple screening procedures are often inaccurate, and this
increases the threat of TB transmission to health-care workers.
It is clear from a public-health perspective that illicit drug use and its
associated risks of HIV and TB are serious threats to the health of non-drug-
addicted populations that justify the investment of federal funds in drug-treatment
research and prevention. The burden of HIV and TB on the health-care system
is important to consider. For example, the CDC spent about $20 million per year
for TB programs in 1967, 1968, and 1969. The expenditure fell dramatically in
1972-1983 but increased to $ 100 million in 1993, mainly because of HIV-related
programs (OTA, 1993~. The average cost of medication to treat uncomplicated
TB is about $350 per person, but medications for a case of drug resistant TB cost
an average of $8,720 and possibly as much as $35,000 (OTA, 1993~.
OCR for page 32
32
DEVELOPMENT OF MEDICATIONS
Health Consequences: Drug-exposed Infants
NIDA's recently released National Pregnancy and Health Survey provides
nationally representative data on the extent of drug use during pregnancy (NIDA,
1994~. The survey estimated that 221,000 women (with 220,000 live births) used
one or more illicit drugs during pregnancy with estimates of 45,100 women
having used cocaine (34,800 of those women used crack cocaine) and 3,600
women having used heroin during pregnancy.
Drug-exposed infants have more medical complications and longer hospital
stays after birth and possibly suffer from long-term developmental deficits (GAO,
1990~. Fetal effects of maternal illicit drug use are difficult to separate, however,
from the many risk factors often present in the lives of drug-using women, such
as infrequent or no prenatal care, poor nutrition, low socioeconomic status, low
maternal age, and multiple drug use, including cigarette-smoking and alcohol.
Frequency of drug use, timing of drug use during pregnancy, drug purity, and
dosage are additional confounding variables.
Cocaine acts as a vasoconstrictor (possibly constricting blood vessels in the
placenta and umbilical cord), and its maternal use during pregnancy has been
found to be associated with impaired fetal growth and lower head size at birth
(Finnegan and Kandall, 1992~. Studies are ongoing to determine the relationship
between prenatal cocaine exposure and birth defects, preterrn birth, and neonatal
neurobehavioral dysfunction, including heightened sensitivity and irritability,
abnormal sleep patterns, and decreased interactive behavior (Peters and Theorell,
1990; Zuckerman, 1991~. Maternal use of opiates increases the likelihood of low
birth weight, prematurity, small fetal head size, and sudden infant death
syndrome (Zuckerman, 1991; Finnegan and Kandall, 1992~. Infants of opiate-
addicted mothers often are addicted and go through the neonatal abstinence
syndrome in withdrawal (Kronstadt, 1991~. Long-term developmental conse-
quences of in utero exposure to illicit drugs including language, behavioral, and
learning difficulties are being studied (Kronstadt, 1991; Zuckerman, 1991~.
ECONOMIC COSTS OF ILLICIT DRUG USE TO SOCIETY
Given the extent of the major health consequences associated with illicit
drug use, the need for treatment? including effective pharmacotherapy, is urgent.
In addition to the public-health imperative for developing these medications, the
economic costs associated with use of illicit drugs are staggering.
It has been estimated that about $66.9 billion (Table 1.2) was spent in 1990
in dealing with some aspect of illicit drug use (D. Rice, University of California
at San Francisco, personal communication). That figure includes costs for health
are, for drug-addiction treatment and prevention, for fighting and preventing
OCR for page 33
INTRODUCTION
~3
J
drug-related crime, and for resources lost because of reduced worker productivity
or death (Figure 1.11. These costs have steadily and substantially risen from an
estimated $44 billion in 1985 to $58 billion in 1988 and to the 1990 estimates
in excess of $66 billion (Rice et al., 1991; Rice, UCSF, personal communica-
tion). Although the focus of this report is on heroin and cocaine, economic costs
are not available for specific drugs, so the data cited here include all illicit drug
use.
TABLE 1.2 Estimated Economic Costs of Drug Abuse, 1990
Type of Cost
Amount Percent
($ millions) Distribution
.
Total66,873 100.0
Core Costs14,602 21.8
Direct3,197 4.8
Mental health organizations867 1.3
Short stay hospitals1,889 2.8
Office-based physicians88 0.1
Other professional services32 0.05
Support costs321 0.5
Indirect11,405 17.1
Morbiditya7,997 12.0
Mortality3,408 5.1
Other related costs45,989 68.8
Direct18,043 27.0
Crime18,035 27.0
Social-welfare administration8 0.01
Indirect27,946 41.8
Victims of crime1,042 1.6
Incarceration7,813 11.7
Crime careers19,091 28.5
AIDS6,282 9.4
NOTE: Within each category are direct costs, for which payment is made, and indirect
costs, for which resources are lost. 1990 costs based on socioeconomic indexes applied
to 1985 estimates.
Defined by the author as the value of goods and services lost by individuals unable to
perform their usual activities because of drug abuse, or unable to perform them at a level
of full effectiveness (Rice et al., 1990~. SOURCE: D. Rice, University of California at
San Francisco, personal communication.
OCR for page 34
34
DEVELOPMENT OF MEDICATIONS
Drug-related crime cost society over $46 billion in 1990 and constitutes the
highest percentage of the economic burden placed on society as a result of illicit
drug use (Table 1.2~. This figure is a composite of the direct costs of police
protection, drug-traffic control, property destruction, and legal adjudication and
the indirect costs of lost productivity for victims of crime and for those incarcer-
ated in prisons or involved in criminal careers. Direct health-related costs of
illicit drug use were estimated to have totaled over $3 billion in 1990, and
health-care costs due to the large number of AIDS cases associated with injection
drug use were-estimated at $6.3 billion in 1990 (Table 1.2~. Other costs of illicit
drug use include morbidity costs (the value of reduced or lost productivity due
to drug use) and mortality costs (the value of productivity lost because of
premature death resulting from drug addiction); these indirect costs were
estimated to total over $11 billion in 1990 in the United States. The social-
welfare costs summarized in Table 1.2 (estimated at $8 million in 1990) include
costs of public assistance, food stamps, unemployment insurance, and other
social-welfare programs.
Crime 68.7%
AIDS 9.4% Mortality 5.1%
Health care 4.8%
Morbidity 1 2.0%
FIGURE 1.1 Summary of the economic cost of illicit drug use, 1990. Percentage
breakdown of $66.9 billion cost of U.S. illicit drug use in 1990. SOURCE: D. Rice,
University of California at San Francisco, personal communication.
Those estimates include federal expenditures. In 1992, the federal govern-
ment spent $11.9 billion on drug control and employed 66,652 persons (full-time
equivalents) to work in various agencies on the illicit drug-use problem
(ONDCP, 1992~. The Department of Justice handled 36 percent of the 1992
expenditure, DHHS received 17 percent, and the Department of Defense received
OCR for page 35
INTRODUCTION
35
11 percent (ONDCP, 1992~. Total drug-control expenditures by the federal
government have increased by more than 750 percent from 1981 to 1993
(ONDCP, 1992~.
U.S. national drug-control policy has focused primarily on supply reduction;
about two-thirds of drug-control expenditure has gone for interdiction, intelli-
gence, incarceration, and other law-enforcement activities (ONDCP, 1992~. The
remaining one-third of the federal drug-control expenditure has been divided
among research and development, treatment, and prevention (Figure 1.2~. The
percentage for research and development has remained virtually unchanged since
1981, varying from 3.5 to 5 percent of the total expenditure (ONDCP, 19921.
While there have been increases in the amount spent on treatment and preven-
tion, the percentage of the total drug-control budget spent for treatment has been
halved from 30 percent in 1981 to a low of 16 percent in 1992.
8
7
a, 6
5
o
c 4
a
._
=
m 3
2
1
-
,,
l
/
1981 1982 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993
+ ROD _ Treatment
_ Prevention D - Law enforcement
l~lGtJRE 1.' Federal drug control budget trends (1981-1993~. NOTE: Figures are in
current dollars. SOURCE: ONDCP, 1992.
The 1994 national drug-control strategy proposed substantial increases in
spending for treatment, and reductions in the percentage spent on law-enforce-
ment supply control efforts (Washington Post, 19941. The strategy called for
increasing the availability of treatment by providing $355 million in new block
grants to states, with the target of treating an additional 140,000 heavy drug users
each year. However, the final legislation approved only a $57 million increase
for state block grants in the FY95 budget.
OCR for page 36
36
DEVELOPMENT OF MEDICATIONS
EXTENT OF ILLICIT DRUG USE
The widespread presence of illicit drug use in the United States is document-
edinsurveys of households, students, and jail end prison inmates (Table 1.3~.
National incidence of illicit drug use was highest in the 1970s (although cocaine
use peaked in the 1980s) and has steadily declined in the past 20 years. However,
a recent survey of junior-high-school and high-school students shows indications
that this decline has halted and there may be a small upturn in illicit drug use
(Johnston et-al., 1994a). Of 1993 high-school seniors surveyed, 42.9 percent
reported ever using illicit drugs, and 18.3 percent reported use in the preceding
month, predominantly marijuana use (Johnston et al., 1994a). Similarly, 14.9
percent of young adults reported using any illicit drug in the preceding month
(Johnston et al., 1994b). Household, prison and jail, and school surveys result in
the following data:3
.
An estimated 77 million Americans have used an illicit drug at
some time in their life (SAMHSA, 1994c).
· An estimated 24.4 million Americans have used an illicit drug
within the last year (SAMHSA, 1994c).
· An estimated 11.7 million Americans have used an illicit drug
within the last month (SAMHSA, 1994c). Of 1993 high-school seniors
surveyed, 18.3 percent reported use of an illicit drug in the last month a
substantial increase from the 14.4 percent of 1992 high-school seniors
(Johnston et al., 1994a).
· Marijuana, the most commonly used illicit drug in the United
States, has been tried by nearly one-third of all Americans, with highest
preceding year use in those 18-25 years old (22.9 percent had used
marijuana in 1993~. Of the 18.6 million Americans estimated to have used
marijuana in 1993, 5.1 million are estimated to have used it weekly
(SAMHSA, 1994c).
· An estimated 4.5 million Americans used cocaine in 1993 (SAMH-
SA, 1994c). The number of heavy cocaine users, using at least once a week,
is estimated at 2.1 million (Hunt and Rhodes, 1992~. Crack, a smokable
form of cocaine, is estimated to have been used by 996,000 Americans in
the last year (SAMHSA, 1994c).
· Heroin statistics are more difficult to obtain from nationwide
surveys because heroin use involves less than 1 percent of the population
3Note that a recent General Accounting Office report warns that use figures,
particularly in household and student surveys, are underestimated in that these surveys
have high nonresponse rates and do not include high-risk groups, such as high-school
dropouts (GAO, 1993~.
OCR for page 37
INTRODUCTION
37
and many heroin-users are not part of a traditional household environment.
It is estimated that there are 1 million recent or frequent heroin-users,
including 0.5 million heroin-addicted individuals (Kreek, 1992~.
Drug use was a direct or contributing factor in 7,532 deaths reported in 1992
to the Drug Abuse Warning Network (DAWN) by 137 medical examiner
facilities in 38 metropolitan areas. Cocaine was the most frequently reported drug
(46 percent), alcohol in combination with other drugs was mentioned in 39
percent of the cases, and heroin or morphine in 39 percent (SAMHSA, 1994b).
Morbidity reports from DAWN indicate that there were about 433,493 drug
abuse-related hospital emergency-room episodes in 1992 (SAMHSA, 1994a).
Alcohol in combination with other drugs was mentioned most frequently, in
nearly one-third of all episodes (more than one drug per episode can be
mentioned), followed in frequency by cocaine (28 percent), and heroin or
morphine (11 percent). Data collection difficulties including changes in sample
composition, nonresponse from data collectors, changes in data collectors, and
coding errors, place limitations on interpreting the DAWN data.
ROLE OF PHARMACOTHERAPY
Given the magnitude of the illicit-drug-use problem, and its economic and
public-health consequences, addressing this issue requires a dedicated effort not
only to develop pharmacotherapies but also to foster prevention, education, and
the use of other kinds of treatment. Pharmacotherapy, as an adjunct to other
treatment modalities, has not received widespread support, in part because of the
lack of patient advocacy and the belief espoused by some that to treat drug
addiction with a medication is merely to substitute one drug for another. That
belief stems largely from the use of methadone maintenance for opiate-addicted
individuals and, although it's a common view, should not be allowed to detract
from the proven success of methadone maintenance programs, which have
allowed many people to become functional and productive (IOM, 1990; OTA,
1990), or to dominate thinking about the treatment of all types of addictions.
Drug addiction is a disease that merits medication for its treatment, like such
other chronic diseases as hypertension, diabetes, and cancer (Miller, 1991~. That
such treatment might not treat root causes of the illness or offer a permanent cure
does not detract from the value of pharmacotherapy in improving both quality
of life and mortality in patients with those diseases.
OCR for page 38
38
Cat
o
._
Cal
o
Cat
._
o
Cat
o
Is
Cat
Cd
m
v)
cn
Cot
o
Cal
00
Cd
Cal
-
-
.=
0 -
a'
V]
A:
._
Cd
o
C:
V]
4-
._
-
-
_.
o
.=
._
a'
;> ~
. _
;> ~
AS
A:
~0
~ ._
._
~ PA
;>
_ U)
:>
can
Vet
a
z z z z z ° V
_ ~ ~ ~ ~_
_ O O _ _- 0 0Z _
~D ~ v~ O ~ ~ ~
. . . . .. . .. ~. ~
O O _ _ O_ 0 ~° C ~- '
~) ~
,o~ ~ ~z vo ~vom
~ ~ w? v~ oo~ ~ ~
vO ~ ~ oo ~°O Vo ~(~} d O
~ ~ ~ - ~ ~ ~
..... ... <,4
0 _ o ~ vO a ~oo =`
o
c~ ~
~~ as
~<: -
~-
_ ~_, ~ ~ ~ ~,
^ ~-
- o
d)
- ~,
~ ~S
V)
m ~
~ ~:
. ~ -
- 0 ~
d~ ~
O
O
~ C~
~ 3
~ V)
-
~ o
. _
d)
~ O
d)
_ ,.O
Ct ~ d)
~ O O
I_ d~ ,=
~ ~:
.^,S O
C~ ~ ~
^ ~ O
_ ._ ~
~ ~ . ~
S ~
O CL
~ ~ ~s
-~: o ~
o ce o
.^
.=
=` d~
_ ~ C~
~ d~
_ :5
U)
O
=0
_
U) - ·=
._
O -~ ~
. ~ -
~ ~ C~
~ ~o, m
-
·^ )
~ ,.~}
Cd ~
~ ·=
;>
._ _
._
Cd O
·~
_
.O
11
O ~
~ z
~ d)
C~ ~
V,
¢ ~
cn :,
· · d)
C: ~
O
~ Cd
O
C~ ~
d)
.=
o
C~
C~
3
d)
V)
o
d)
~:
d)
OCR for page 39
INTRODUCTION
39
Many illnesses combine both biological and behavioral components. Cardio-
vascular disease, for example, can be caused by an inherited tendency toward
high cholesterol concentrations and be exacerbated by eating habits that increase
dietary fat intake. Its treatment often consists of interventions to change the diet
and, when necessary, drugs to lower cholesterol concentration. Similarly, the
optimal treatment in diabetes might involve a combination of dietary manage-
ment and drug therapy; some people do well with dietary management alone,
others need a combination of dietary management and oral antidiabetes drugs or
insulin. Likewise,-some opiate-addicted individuals do well with supportive
therapy after only a short time on methadone; others require methadone therapy
for the rest of their life.
Whether the methadone model will apply directly to other addictive drugs,
such as cocaine, is not clear. Cocaine is a more complex drug pharmacologically,
and a good substitute that is less abusable has not yet been found. The important
point is that there is no inherent reason why pharmacological therapy cannot play
as important a role in the treatment of drug addiction as other medicinal agents
do in the treatment of heart disease, diabetes, and a host of other illnesses.
The pharmaceutical industry has not responded to this urgent need. Since the
1960s and the acceptance of methadone as the treatment of choice for opiate
addiction, no pharmacotherapies for cocaine addiction have been approved, and
only in the last 10 years have two medications been approved for opiate
addiction (levo-alpha-acetylmethadol [LAAM] and naltrexone).
In an effort to determine the status of pharmaceutical industry participation
in the development of anti-addiction medications, the committee queried the FDA
about the numbers of companies submitting investigational new drug applications
(INDs) for anti-addiction medications. FDA's response indicates that there are
six pharmaceutical companies with INDs for medications to treat opiate or
cocaine addiction (C. Moody, FDA, personal communication). Currently there
are 37 INDs for the treatmen' of drug addiction, but only 18 different drugs are
represented. The FDA reports that 5 or 6 INDs are entering phase III clinical
trials, however only one IND represents a new substance. Three companies have
submitted new drug applications (NDAs) for anti-addiction medications.
The committee was asked to determine the reasons for the lack of activity
in the development of anti-addiction medications. It became evident that many
factors contribute, including: an inadequate science base on addiction and the
prevention of relapse (especially for cocaine); an uncertain market environment
(which includes such issues as: treatment financing, lack of trained specialists for
the treatment of drug addiction, federal and state regulations, market size, pricing
issues, societal stigma, liability issues, difficulties in conducting clinical
research); and a lack of sustained federal leadership. Although for a certain
segment of the pharmaceutical industry (e.g., small companies, biotechnology
companies, or those companies already involved in the development of central
OCR for page 40
40
DEVELOPMENT OF MEDICATIONS
nervous system medications) there may be an interest with suitable incentives to
proceed with development of arlti-addiction medications.
Chapter 2 examines the state of the scientific knowledge concerning opiate
arid cocaine addiction, the approaches used by NIDA's Medications Development
Division to discover medications for cocaine addiction, and the advantages and
limitations of those approaches. In Chapter 3, the background and progress of
MDD are addressed. Chapters 4-9 examine the obstacles and disincentives faced
by the private sector in the development of anti-addiction medications and policy
and legislative solutions are presented. Chapters 4 and 5 address drug-abuse treat-
ment the setting, effectiveness, cost-effectiveness, and the impact of treatment
financing on drug development. The need for increased training and education
of both specialists and primary care physicians in drug-abuse research and
treatment is the focus of Chapter 6. The following two chapters examine the
extent and impact of federal (Chapter 7) and state (Chapter 8) laws and
regulations on anti-addiction medication development, marketing, and treatment.
The report concludes in Chapter 9 with a discussion of additional marketing
obstacles, leadership issues, and outlines steps necessary for increasing private
sector involvement in the development of anti-addiction medications.
REFERENCES
Barnes PF, Bloch AB, Davidson PT, Snider DE Jr. 1991. Tuberculosis in patients with
human immunodeficiency virus infection. New England Journal of Medicine
324:1644-1650.
BJS (Bureau of Justice Statistics). 1991. Drugs and Jail Inmates, 1989. Washington, DC:
BJS.
BJS (Bureau of Justice Statistics). 1992. Drugs, Crime, and the Justice System. Washing-
ton, DC: Government Printing Office. NCJ-1335652.
BJS (Bureau of Justice Statistics). 1993. Survey of State Prison Inmates, 1991.
Washington, DC: BJS. NCJ-136949.
Braun MM, Cote TR, Rabkin CS. 1993. Trends in death with tuberculosis during the
AIDS era. Journal of the American Medical Association 269:2865-2868.
Bray RIM, Kroutil LA, Luckey JW, Wheeless SC, Iannacchione VG, Anderson DW,
Marsden ME, Dunteman GH.1992.1992 Worldwide Survey of Substance Abuse and
Health Behaviors Among Military Personnel. Research Triangle Park, NC: Research
Triangle Institute. RTI/5154/06-16FR.
CDC (Centers for Disease Control and Prevention). 1993a. Tuberculosis prevention in
drug-treatment centers and correctional facilities: selected U.S. cities, 1990-1991.
Morbidity and Mortality Weekly Report 42:210-213.
CDC (Centers for Disease Control and Prevention). 1993b. Tuberculosis morbidity:
United States, 1992. Morbidity and Mortality Weekly Report 42:696-704.
CDC (Centers for Disease Control and Prevention). 1994. HIV/AIDS Surveillance Report
6~1~:8-12.
OCR for page 41
INTRODUCTION
41
Finnegan LP, Kandall SR. 1992. Maternal and neonatal effects of alcohol and drugs. In:
Lowinson JH, Ruiz P. Millman RB, eds. Substance Abuse: A Comprehensive
Textbook. 2nd ed. Baltimore: Williams & Wilkins.
GAO (General Accounting Office). 1990. Drug-Exposed Infants: A Generation at Risk.
Washington, DC: GAO. GAO HRD-90-138.
GAO (General Accounting Of fice). 1993. Drug Use Measurement, Strengths, Limitations,
and Recommendations for Improvement. Washington, DC: GAO. GAO PEMD-93-
18.
Goldstein A. 1994. Most new cases of AIDS in D.C. hit drug users. Washington Post,
December I, 1994:A1.
Hahn RA, Onorato IM, Jones TS, Dougherty J.1989. Prevalence of HIV infection among
intravenous drug users in the United States. Journal of the American Medical
Association 261:2677-2684.
Hardy LM. 1991. HIV Screening of Pregnant Women and Newborns. Washington, DC:
National Academy Press.
Hunt DE, Rhodes W. 1992. Characteristics of Heavy Cocaine Users Including Polydrug
Use, Criminal Activity, and Health Risks. Prepared for the Office of National Drug
Control Policy by Abt Associates, Inc.
IOM (Institute of Medicine). 1990. Treating Drug Problems. Gerstein DR, Harwood HJ,
eds. Washington, DC: National Academy Press.
Johnston LD, O'Malley PM, Bachman JG. 1994a. National Survey Results on Drug Use
from The Monitoring the Future Study, 1975-1993. Vol. I, Secondary School
Students. Rockville, MD: NIDA. NIH Publication No. 94-3809.
Johnston LD, O'Malley PM, Bachman JG. 1994b. National Survey Results on Drug Use
from The Monitoring the Future Study, 1975-1993. Vol. II, College Students and
Young Adults. Rockville, MD: NIDA. NIH Publication No. 94-3810.
Koop CE, Lundberg GD. 1992. Violence in America: a public health emergency. Journal
of the American Medical Association 267:3075-3076.
Kreek MJ. 1992. Rationale for maintenance pharmacotherapy of opiate dependence. In:
O'Brien CP, Jaffe JH, eds. Addictive States. New York: Raven Press. 205-230.
Kronstadt D. 1991. Complex developmental issues of prenatal drug exposure. The Future
of Children 1:35~9.
Marwick C. 1992. Guns, drugs threaten to raise public health problem of violence to
epidemic. Journal of the American Medical Association 267:2993.
!\/Iiller NS. 1991. Drug and alcohol addiction as a disease. In: Miller NS, ed. Comprehen-
sive Handbook of Drug and Alcohol Addiction. New York: Marcel Dekker. 295-310.
Miller NS, Gold MS, Mahler JC. 1991. Violent behaviors associated with cocaine use:
possible pharmacological mechanisms. International Journal of Addiction
26:1077-1088.
NIDA (National Institute on Drug AbuseJ. 1994. National Pregnancy and Health Survey.
Prepared by Westat, Inc. P~ockville, MD: NIDA.
NIJ (National Institute of Justice). 1992. Drug Use Forecasting 1991 Annual Report.
Washington, DC: NIJ. NCJ 137776.
ONDCP (Off~ce of National Drug Control Policy). 1992. National Drug Control Strategy:
A Nation Responds to Drug Use. Budget Summary. Washington, DC: ONDCP.
OCR for page 42
42
DEVELOPMENT OF MEDICATIONS
OTA (Office of Technology Assessment). 1990. The Effectiveness of Drug Abuse
Treatment: Implications for Controlling AIDS/HIV Infection. Washington, DC: OTA.
OTA-BP-H-73. AIDS Related Issues Background Paper 6.
OTA (Office of Technology Assessment).1993. The Continuing Challenge of Tuberculo-
sis. Washington, DC: U.S. Government Printing Office. OTA-H-574.
Peters H. Theorell CJ. 1990. Fetal and neonatal effects of maternal cocaine use. Journal
of Obstetric, Gynecologic, and Neonatal Nursing 20: 121-126.
-Rice DP, Kelman S. Miller LS, Dunmeyer S. 1990. The Economic Costs of Alcohol and
Drug Abuse and Mental Illness: 1985. San Francisco: University of California,
Institute for Health and Aging. DHHS Publication No. (ADM) 90-1694.
Rice DP, Kelman S. Miller LS. 1991. Estimates of economic costs of alcohol and drug
abuse and mental illness, 1985 and 1988. Public Health Reports 106:280292.
Rosenberg ML, O'Carroll PW, Powell KE. 1992. Let's be clear violence is a public
health problem. Journal of the American Medical Association 267:3071-3072.
SAMHSA (Substance Abuse and Mental Health Services Administration). 1994a. Annual
Emergency Room Data 1992. Data from the Drug Abuse Warning Network Series
1, Number 12-A. Rockville, MD: NIDA. DHHS Publication No. (SMA) 94-2080.
SAMHSA (Substance Abuse and Mental Health Services Administration). 1994b. Annual
Medical Examiner Data 1992. Data from the Drug Abuse Warning Network Series
1, Number 12-B. Rockville, MD: NIDA. DHHS Publication No. (SMA) 94-2081.
SAMHSA (Substance Abuse and Mental Health Services Administration, Office of
Applied Statistics). 1994c. PreliminaIy Estimates From the 1993 National Household
Survey on Drug Abuse. Rockville, MD: SAMHSA. Advance Report Number 7, July
1994.
Schneider D, Greenberg MR, Choi D. 1992. Violence as a public health priority for black
Americans. Journal of the National Medical Association 84:843-848.
Turner CF, Miller HG, Moses LE. 1989. AIDS, Sexual Behavior and Intravenous Drug
Use. Washington, DC: National Academy Press.
U.S. Congress, Senate.1989. Committee on the Judiciary. Staff Report. Pharmacotherapy:
A Strategy for the 1990's. 101 st Cong., 1 st sess. S. Prt. 101 -000.
U.S. DHHS (U.S. Department of Health and Human Services). 1992. Maternal Drug
Abuse and Drug Exposed Children: A Compendium of HHS Activities. Washington,
DC: GPO. DHHS Publication No. (ADM) 92-1948.
Washington Post. 1994. Clinton drug policy focuses on treating hard-core users.
Washington Post. February 9, 1994. A6.
Zuckerman B. 1991. Drug-exposed infants: understanding the medical risk. The Future
of Children 1:28-35.
Representative terms from entire chapter:
drug abuse
