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Chapter 3 PUBLIC HEALTH PROBLEMS ASSOCIATED WITH USE OF HYPNOTIC DRUGS The availability of hypnotics and tranquilizers to relieve insomnia and anxiety imposes burdens on the public, including mortality from drug overdose, whether intentional or accidental; the treatment of nonfatal overdose emergencies; the increased crime and lost production due to abuse of and addiction to these drugs; and the increased mortality and morbidity from traffic and industrial accidents caused by people whose functioning is impaired by drugs. Although economists have imputed dollar costs to some of these problems, 1/ this chapter only describes the problems in terms of the number of people affected. There is no national system to monitor the extent of drug misuse and abuse, and thus it is impossible to draw con- clusions about relationships between drug problems deriving from normal medical practice and those of use of drugs for non-medical purposes. The importance of the data problem is suggested by a study of suicides committed in St. Louis County, Missouri, in 1968 and 1969. The author found that at least 16 of 32 persons who committed suicide with drugs had recently been given prescriptions for hypnotics in amounts that were potentially lethal. The prescribed drugs apparently were used in the suicide in most of the 16 cases. 2/ If such a pattern could be proved on a national scale, the policy implications for closer moni- toring of prescription size and refills would be clear. In one study, two-thirds of suicides had been preceded by medical visits in the pre- vious 4 to 6 weeks; 7/ however, the direct source of the drugs used in most suicides, or implicated in accidental overdose deaths, is not readily available information. Because the focus of this study is the use of prescription drugs, the following discussion does not include adverse effects of alcohol alone. However, as has been described in Chapter 1 of this report, the combination of hypnotics or tranquilizers with alcohol can prove fatal. A. Suicide and Accidental Overdose In 1976, almost 27,000 suicides were reported, constituting about one percent of all deaths. 3/ Firearms and hanging were the means used most often; drugs have been in the third place since the early 1960s, and were reported in 11 percent of suicide deaths in 1976 (Table 1~. -63-

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It has been suggested that suicides are under-reported by as much much as 100 percent, 4/ and that many of those not reported are due to drugs. The reasons for this include the general reluctance of some coroners or medical examiners to assign a death as suicide unless the evidence is very clear. Many coroners offices do not have the necessary toxicological facilities or staff to establish the fact of a drug overdose. 5/ If all suicides were accurately reported, it is possible that ingestion of drugs would be the second most common means. Male suicide rates in the United States are three times as high as those for females, and rates for whites are twice as high as for blacks. In recent years, however, suicide rates for black males have been e ncreas 1ng. Suicide rates tend to increase with age. In the past twenty years, however, the increase in the number of suicides committed by young people has outraced their numerical increase as a segment of the population. The result is that age differences in suicide rates have become less dramatic. For example, the suicide rate for the 20 to 24 year age group in 1955 was slightly more than 5 per 100,000, compared with 25 for the 65 to 69 year group. In 1975, the comparable rates were 17 and 19, respectively. Increases of similar magnitude in the suicide rates were seen in each five year age group through age 34 during this 20 year period. This increase in suicide rates among the younger age groups, together with evidence of increasingly widespread use of drugs for intoxication 6/ and the growing use of drugs as a means of suicide, led to much \of the demand during the 1960s for controls on prescription drugs, particularly barbiturates. In 1954, barbiturates were reported as the cause of death in four percent of the 16,000 suicides in the United States and in 84 percent of the 865 drug-related suicides. During the next ten years, suicide deaths in which drugs were used increased more than threefold to 2,666, with barbiturate deaths accounting for most of the increase. In 1963, barbiturates were used in ten percent of all suicides, accounting for for 75 percent of drug suicides. By 1968, although the number of drug suicides remained at about 2,600, barbiturates were identified as the means of death in only 61 percent of the cases; use of other drugs was increasing. A sharp drop in numbers of prescriptions written for barbiturates from 1970 to 1976 was paralleled by a decrease in suicides using these drugs (Figure 1~; by 1976, they accounted for only 30 percent of drug suicides (Table 2~. Although there was a 50 percent drop in the barbiturate suicide rate from 1970 to 1976, the overall rate of suicides from drugs declined 65

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(41 .1) 4000 3500 cn LL ~~' 3000 an UJ 2500 A: UJ co ~ 2000 11 o m 15 1 000 500 \ - Barbiturate Prescriptions \~`Right-hand scale) I _ - ~ S`uicides Al I Drugs ! (Left-hand scale) J ~- _ - _N - \~ Barbiturate Suicides \ (Left-hand scale) - _. 1. 1 1 1 1 1 1 1969 1971 1973 1975 1977 YEAR Source: National Center for Health Statistics, Mortality Branch National Prescription Audit, IMS America, Ltd. 66- 40 _ 35 _ 30 25 - oh 15 ~ cut 10 5

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only 13 percent. The total number of drug suicides remained stable, due partly to the growing use of antidepressants and tranquilizers (Table 2~. However, the largest proportion of suicides were committed using drugs coded as "other and unspecified." 8/ Despite some methodological weaknesses, 9/ data reported from the Drug Abuse Warning Network (DAWN) indicate the relative involvement of different drugs. 10/ Medical examiners reported 3,464 deaths from May 1976 to April 1977. Heroin, or its metabolite, morphine, was identified in 1,079 of these deaths; in 421 of these it was the only drug mentioned. D-Propoxyphene (Darvon(R)) was the second drug most often mentioned being cited in 421 deaths; in 160 deaths, it was the only drug mentioned. Although diazepam (Valium(R)) was the next most-often mentioned drug, it was reported as used alone in only 19 of the 317 deaths in which it was involved. The single barbiturate most often reported in the DAWN deaths was secobarbital. This drug was involved in 299 deaths; in 102 deaths it was used alone, according to the medical examiner report. Over half the reported drug overdose deaths involved the use of more than two substances, although an examination of the deaths in which multiple drugs were used shows the pervasiveness of alcohol. 11/ In Los Angeles county, where there are about 1,200 drug deaths a year, barbiturates are most commonly the drugs involved. However, the mortality rate in the county from barbiturates fell from 9 per 100,000 population in 1972 to 7.5 in 1975. Data from the medical examiner's office show a compensating increase in the numbers of drug deaths due to the use of 'other hypnotics and various antidepressants and tranquil- izers," as well as in deaths due to combinations of drugs with alcohol. Additionally, an increase in drug deaths involving d-propoxyphene (Darvon (R)) has been recorded in Los Angeles, along with an increasing tendency for suicides to "clear out the medicine cabinet." 12/ The office estimates that as much as 84 percent of all drug deaths in Los Angeles involve more than one drug. Similar patterns, although on a much smaller scale, are reported for 1976 and 1977 in Onondaga County, New York, which includes the city of Syracuse. In 1976, eight of 21 drug deaths involved the use of a barbiturate. One year later, of 24 deaths involving drugs, only two involved a barbiturate; diazepam, d-propoxyphene, and alcohol were the most frequently mentioned drugs, in combination with each other or other antidepressants, major tranquilizers, non-barbiturate hypnotics and minor tranquilizers. -68-

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Although suicides from all drugs have fallen about 13 percent since 1970, deaths from accidental overdose have risen about 7 percent. Much of this increase, both in the numbers of deaths and the mortality rates, has occurred in the 20 to 29 year age group which also has high rates of use of over-the-counter drugs and alcohol (Tables 3 and 4~. Some of the increase is believed due to the combination of alcohol and drugs thought of as "safe," such as diazepam. Alcohol has been shown to be involved in many drug-related deaths, and the potential lethality of drug-alcohol combinations probably is not fully appreciated by physicians, their patients, or persons combining these drugs. Although in 1976 people over 65 accounted for only 11 percent of the population, they accounted for 15 percent of all drug-involved suicides. However, the elderly receive 25 percent of prescription drugs and more than 30 percent of tranquilizers and hypnotics, so that in terms of drug availability they could be described as under- represented among drug suicides. 13/ At the other end of the age scale, the 15 to 24 year group receives only about nine percent of prescription drugs and seven percent of sedative-hypnotics, yet they account for 15 percent of drug suicides. 14/ Suicide Attempts In addition to 7,500 to 8,000 deaths a year from intentional drug overdose, it has been estimated that there are eight to 16 times as many failed attempts at suicide with drugs. One study reports drugs to be used in 48 percent of cases, which suggests a conservative estimate of about 100,000 suicides attempted annually with use of drugs. 16/ About two-thirds of such attempts are made by women. _ /,17/ Physicians questioned about the seriousness of intent of their patients attempting suicide with drugs have estimated that only about one-third wanted to die. 16/,18/ Suicide attempts with drugs may be impulsive acts that might have less serious consequences if the amount of the drugs made available were more severely restricted. When the size of single prescriptions for barbiturates was restricted in Australia, there was a decline in barbiturate suicides; there was no compensatory increase in suicides by other means. 15/,19/ More appropriate prescribing, a restriction on the size of a single prescription, and monitoring of refills, could save lives. 7/,19/ -69-

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TABLE 3. DRUG-RELATED SUICIDES AND ACCIDENTAL OVERDOSE DEATHS (1968-1976) Suicides Accidental Overdose Deaths Age Groups < 10 10-14 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80+ 6 110 162 189 205 250 319 288 286 273 186 139 109 64 49 All Ages 2635 1968 1970 1972 1974 1976 12 174 384 303 238 278 32-6 326 287 254 216 181 134 74 82 3251 16 16 16 144 133 135 366 292 326 316 335 354 264 275 300 268 232 268 306 270 258 318 281 254 270 296 255 260 217 224 252 156 183 160 145 146 122 107 120 64 90 86 96 60 81 3222 2904 3002 1968 1970 1972 1974 1976 160 132 154 89 83 10 22 171 332 245 534 191 301 167 209 140 153 141 165 101 132 89 127 76 102 56 88 44 57 41 48 30 38 30 64 1692 2505 18 290 544 374 152 144 144 146 84 102 110 50 52 70 80 2516 Source: U.S. Department of Health, Education and Welfare, National Center for Health Statistics, Mortality Branch -70- 16 16 281 189 610 656 468 578 250 281 164 185 156 154 141 125 100 118 101 98 96 89 69 68 63 51 51 57 84 99 2742 2839

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TABLE 4. DRUG-RELATED SUICIDES AND ACCIDENTAL OVERDOSE RATES PER 100,000 POPULATION (1968-1976) Suicide Rate Accidental Overdose Rates Age Groups 1968 1970 1972 1974 1976 1968 1970 1972 1974 1976 o 10-14 .03 .06 .08 .08 .05 .05 .11 .09 .08 .08 15-19 .06 .92 .73 .65 .65 .99 1.75 1.46 1.37 .01 20-24 1.11 2.47 2.15 1.63 1.73 1.68 3.44 3.20 3.41 3.49 25-29 1.50 2.28 2.15 2.11 2.03 1.51 2.26 2.54 2.95 3.32 30-34 1.88 2.10 2.19 2.07 2.14 1.53 1.85 1.26 1.88 2.00 35-39 2.21 2.55 2.45 2.06 2.29 1.24 1.40 1.32 1.46 1.58 40-44 2.57 2.74 2.64 2.39 2.33 1.14 1.39 1.24 1.38 1.39 45-49 2.43 2.69 2.65 2.38 2.18 .85 1.09 1.22 1.19 1.07 50-54 2.62 2.58 2.32 2.48 2.13 .81 1.14 .72 .84 .99 55-59 2.82 2.54 2.57 2.10 2.08 .78 1.02 1.01 .98 .91 60-64 2.21 2.49 2.80 1.69 1.97 .67 1.01 1.22 1.04 .96 65-69 2.05 2.58 2.16 1.85 1.76 .65 .81 .68 .88 .82 70-74 2.07 2.45 2.21 1.88 2.12 .78 .88 .94 1.10 .86 75-79 1.72 1.90 1.62 2.29 2.12 .81 .98 1.77 1.30 1.41 80 ~ 1.38 2.19 2.38 1.38 1.72 .85 1.71 1.98 1.93 2.11 All Ages 1.31 1.61 1.56 1.38 1.41 .84 1.24 1.22 1.31 1.33 Source: U.S. Department of Health, Education and Welfare, National Center for Health Statistics, Mortality Branch.

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B. Traffic Safety There have been few studies in the United States to determine the role of drugs in traffic accidents, although the role of alcohol in traffic accidents has been widely studied and a cause and effect rela- tionship is generally recognized. 20/ In a study of 100 victims of automobile accidents in North Carolina (both drivers and pedestrians), alcohol alone was found in 46 percent of the cases, and a drug plus alcohol was found in three percent of the victims. Drugs alone were found in only five victims, all pedestrians. More than 80 percent of the victims in whom alcohol was found would have been considered legally drunk. 21/ In another study of 503 fatally injured drivers from all parts of the United States, 11 percent evidenced a sedative or hypnotic drug in their blood or urine. Of these, 54 percent also evidenced non-zero blood alcohol levels and in about 45 percent of cases, these concen- trations were above 0.10 percent, the legal definition of intoxication in most states. 22/ Norwegian researchers compared findings from blood samples obtained from 74 non-fatal traffic accident victims to those from a control group of 204 people not involved in accidents. Forty-six percent of the accident victims had blood alcohol concentrations in the intoxicated range; 11 percent showed diazepam in the blood sample, about half of these at the high end of the therapeutic range; a further 8 percent showed both alcohol and diazepam present. These findings were compared to the reference group in which alcohol or diazepam was found in only three percent of cases, and in no case were the two substances found together. One person in the reference group had a blood alcohol concentration above the intoxicated level. 23/ In a similar Finnish study, diazepam alone was found in five percent of injured drivers compared to two percent of a control group. 24/ These data indicate an association between diazepam and non-fatal traffic accidents 9 but further studies and baseline data are needed before a causal relationship can be demonstrated. Both studies confirm, however, that the use of alcohol remains the pre- dominant traffic safety hazard. Apart from the ubiquity of alcohol in traffic accidents, there are other problems in establishing a causal role for drugs. First, there are no reliable estimates of the use of hypnotic drugs among the driving population in the Onited States, so it is difficult to establish whether the proportion of accident victims in whom drugs are found deviates from the expected value based on general popula- tion use. -72-

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Second, the detection of drugs and the measurement of their levels varies depending on such factors as the screening method used, the sen- sitivity of the instruments used, and the method of handling samples from the accident site to the laboratory. The last is especially important since many drugs are chemically unstable even in dead tissue, unless it is frozen. 25/ Third, until recently, there has been a tendency in most studies to screen blood and urine samples for the relatively easily detected drugs such as alcohol, opiates, and the barbiturates, while toxico- logical testing for the most widely prescribed drugs, diazepam and flurazepam, has been rare. More information should be forthcoming now that relatively simple tests have been devised for assaying serum levels of N-desalkylflurazepam (flurazepam's long-acting metabolite), diazepam, and N-desmethyldiazepam (diazepam's long-acting metabo- lite). 26/ C. Non-medical Use of Drugs The National Institute on Drug Abuse has for several years conducted a survey of the extent of non-medical use of drugs by the general population (Table 5~. 27/ "Non-medical use" was defined as a report by the respondent that a particular drug was used "to see what it was like" or "to enjoy the feeling it gave" and "not because it was needed." Although the number of responses is too small to project to the total population, it is worth noting that 85 percent of the users of these drugs were 18 to 25 years old, the group least likely to receive them through a prescription. In a survey during 1976, the 1,800 clinics that receive federal funds for drug treatment programs reported 210,000 admissions. Sixty- four percent of those admitted reported their primary drug of abuse was heroin or another opiate; barbiturates were reported by almost five percent, or about 9,800 people. Forty-five percent of the barbiturate abusers were younger than 21, although only 21 percent of all admissions were in this age group. 28/* *About 30 percent of clients citing barbiturates as their primary drug of abuse indicated current usage of less than once a month, and another 18 percent indicated using the drug once a week or less. It is difficult, therefore, to understand what level of abuse or addiction the CODAP data represent. -73-

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Adults 18+ N=2,411 N=3,071 N=2,590 N=3,222 TABLE 5. NON-MEDICAL USE OF DRUGS IN PAST MONTH (1972-1977) 1972 1974 1976 1977 1976-1977 change Marihuana and/or hashish 8.0 a/ 7.0 7.9 8.2 NS Inhalants * * * * NS Hallucinogens .7 .6 * .5 NS Cocaine .9 .7 .7 1.0 NS Heroin * * * * NS Other Opiates 11 * * * b/ Stimulants (Rx) ~ 1.0 1.2 1.0 NS b/ Sedatives (Rx) ~ * .9 .6 NS b/ Tranquilizers (Rx) ~ * .8 .8 NS Alcohol 11 58.0 58.8 58.0 NS Cigarettes ~ 41.0 40.7 40.5 NS a/ _/ Marihuana only Non-medical use. Estimates in 1977 based on split sample: N=1647. *Less than .5% NS: not significant; : significance level not calculated because categories not comparable. Snot asked. Source: National Institute on Drug Abuse, National Survey on Drug Abuse: 1977, Volume 1, Main Findings. (Table 11~. - 74 -

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These treatment programs represent about half of all known drug treatment programs in the United States. Clients usually enter the programs when their drug use interferes with their daily functioning. They may be admitted on a voluntary basis or referred from such agencies as the Bureau of Prisons or the Veterans Administration. Another survey indicates that units that do not receive federal funds treat about the same number of clients, which suggests that there are about 20,000 people with a recognized problem with barbiturates in the United States. 29/ The extent of the problems with the benzodiazepines is especially difficult to ascertain but is a source of growing concern in the medical community. _ /-33/ Data for the first quarter of 1978 indicate that about 2,400 people sought treatment of a primary problem with any kind of tranquilizer or non-barbiturate hypnotic drugs. 34/ This suggests that each year there are at least 5,000 people in federal programs whose functioning is impaired by dependence on tranquilizers, and another 4,000 with problems deriving from the use of non-barbiturate hypnotics. Again, assuming a similar number in non-federal programs, there appear to be at least 19,000 people with a primary problem related to the use of non-barbiturate tranquilizers and hypnotics. Barbiturates represent a secondary drug of abuse for five percent of federal program clients; tranquilizers and other hypnotics are secondary drugs of abuse for four percent. After eliminating duplicate counting of individuals whose primary and secondary drugs of abuse are both tranquilizers or hypnotics, it appears there are about 32,000 people for whom these drugs represent a secondary problem. 34/ -75-

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REFERENCES 1 2 3 4 5 6 7 8 9 10 National Institute on Drug Abuse, Management Effectiveness Measures for NIDA Drug Abuse Treatment Programs, Vol. II: Costs to Society of Drug Abuse. U.S. Government Printing Office, Washington, D.C., 1976. Murphy, G.E., The physicianrs responsibility for suicide. 1. An error of commission. Annals of Internal Medicine, Vol. 82: 301-304, 1975. National Center for Health Statistics, Division of Vital Statistics, Mortality Branch. HEW, National Center for Health Statistics, Suicides in the United States 1950-1964, Vital and Health Statistics, Series 20, Number 5, (Rockville: DREW Pub. No. HSM 73-1259), 1967 Farberow, N.L., McKinnon, D.R. and Nelson, F.L., Suicide: Who's counting? Public Health Reports, 92, No. 3, pp. 223-232. Johnston, L.D., Drug use during and after high school: Results of a national longitudinal study, American Journal of Public Health Supple- ment, 64: 29-37, 1974. Barraclough, B., Bunch, J., Nelson, B., and Sains bury, P., A Hundred Cases of Suicide: Clinical Aspects. British Journal of Psychiatry, 125:355-73, 1974. Department of HEW, Eighth Revision International Classification of Diseases, National Center for Health Statistics (Washington, D.C.: GPO), 1975. Lasagna, L., DAWN's early light: A flickering flame. The Sciences (New York Academy of Science), November/December, 1976. Drug Enforcement Administration and National Institute on Drug Abuse. Project DAWN V, U.S. Government Printing Office: 1978. . 76

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DAWN Tape - As of January 7, 1977. 12 13 14 15 16 17 18 19 20 21 Nakamura, G.R. and Noguchi, T.T., The Current Trend in Drug Deaths in Los Angeles County, 1976. Dept. of the Chief Medical Examiner-Coroner, County of Los Angeles, manuscript. Davis R. and Smith, W. (eds.) Drugs and the Elderly, (Ethel Percy Andrus Gerontology Center: University of Southern California), 1975. National Center for Health Statistics, Cost and Acquisition of Prescribed and Non-prescribed Medicines, United States July 1964- June 1965: Series 10, No. 23. (tTo S. Government Printing Office: Washington, D.C.), 1966. Edwards, J.E. and Whitlock, F.A., Suicide and attempted suicide in Brisbane: 1, Medical Journal of Australia, 1968. Shneidman, F.S. and Farberow, N.L., Statistical comparisons between attempted and completed suicides, in The Cry for Help, (McGraw-Hill, Inc.: New York), 1961. Wold, C.I., Characteristics of 26,000 suicide prevention center patients, Bulletin of Suicidology 6: 24-28,1970. Whitlock, F.A. and Schapira, K., Attempted suicide in Newcastle upon Tyne, British Journal of Psychiatry 113: 423-434, 1967. Barraclough, B.M., Nelson, P., Bunch, J. and Sainsbury, P., Suicide and barbiturate prescribing, Journal of the Royal College of General Practitioners 21: 645-653, 1971. Linnoila, M., Tranquilizers and driving, Accid. Anal. and Prev. 8: 15-19, 1976. Turk, R.F., McBay, A.J., and Hudson, P., Drug involvement in automobile driver and pedestrian fatalities, Journal of Forensic Sciences 19: 90-97, 1974. - 77 -

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22 23 24 25 26 27 28 29 30 U.S. Dept. of Transportation, National Highway Traffic Safety Administration. Drum Use Among Drivers, National Techincal Informa- tion Service, Va. 1975. Bo, O., Haffner, J.F.W., et al, Ethanol and diazepam as causative agents in road traffic accidents. (Proceedings of the 6th Inter- national Conference on Alcohol, Drugs, and Driving, Toronto, 1976). Linnoila, M., Psychomotor effects of drugs and alcohol on healthy volunteers and psychiatric patients. Proceedings of the 7th International Conference in Pharmacology, Paris 1978, (Pergamon Press: New York, in press). O.S. Department of Transportation' National Highway Traffic Safety Administration, Report of an International Symposium on Drugs and . Driving. National Technical Information Service, 1975. Linnoila, M., Dorrity, F., Rapid gas chromatographic assay of serum diazepam, N-desmethyldiazepam, N-desalkyflurazepam; Acta Pharmacologia et Toxicology, 41: 458-464, 1977. National Institute on Drug Abuse, National Survey on Drug Abuse: 1977 Vol. 1. Main Findings. DREW Publication No. (ADM) 78-618, U.S. Government Printing Office, Washington, D.C. 1977. National Institute on Drug Abuse, Sc~ciscical Series, Annual Summary Report 1977, Data from the Client Oriented Data Acquisition Process - (CODAP), Series E, Number 1, DHEW Publication No. (ADM) 78-547. National Institute on Drug Abuse, Statistical Series, Executive Report April 1977, Data from the National Drug Abuse Treatment Utilization Survey (NDATUS), Series F. Number 3, DHEW Publication No.(ADM) 77-534. Ryan, H.F., Merrill, F.B. et al., Increase in suicidal thoughts and tendencies: Association with diazepam therapy. Journal of the American Medical Association 203: 135-137, 1968. -78-

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31 32 33 34 Maletzky, B.M. and Klotter, J., Addiction to diazepam, Journal of the Addictions 11: 95-115, 1976. Internationa : Woody, G.E., O'Brien, C.P. and Greenstein, R., Misuse and abuse of diazepam: An increasingly common medical problem. Journal of the Addictions, 10: 843-848, 1975 International Hollister, L.E., Motzenbecker, F.P. and Degan, R.O., Withdrawal reactions from chlordiazepoxide ("Librium"~. Psychopharmacologia 2:63-68, 1961. National Institute on Drug Abuse Statistical Series, Quarterly Report, Provisional Data January-March 1978, Series D, Number 6, DREW Publica- tion (ADM) 78-726. -79-

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