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December 16, 1988, Vol 260, No. 23 >
ARTICLE | December 16, 1988

Use and Abuse of Benzodiazepines: Title and subTitle BreakIssues Relevant to Prescribing FREE

James H. Woods, PhD; Jonathan L. Katz, PhD; Gail Winger, PhD
[+] Author Affiliations

The views expressed herein are those of the authors and do not necessarily reflect the views of the agencies or institutions with which the authors are affiliated nor of the organizations providing funds for this work.

Reprint requests to M6322 Medical Science 1, The University of Michigan Medical School, Ann Arbor, MI 48109 (Dr Woods).


JAMA. 1988;260(23):3476-3480. doi:10.1001/jama.1988.03410230094036
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References

THE WIDESPREAD use of benzodiazepines has been a source of concern and debate, due in large part to the traditional association of "mood-altering" or sedating drugs with problems of abuse and dependence. Such problems have indeed been reported with the benzodiazepines, and the view has emerged that abuse and dependence might account for a substantial proportion of benzodiazepine use. On the other hand, many investigators1-5 have found that most use of benzodiazepines is appropriate to the prevalence of the medical and psychiatric conditions for which they are deemed effective. Physicians prescribing these drugs are faced with the need to weigh the potential risk to their patients against the drugs' demonstrated benefit in the treatment of anxiety and insomnia.

We have recently conducted a comprehensive review of the extensive experimental, clinical, and epidemiologic literature pertinent to the use and abuse of benzodiazepines.6 Our review indicates that these two predominant

REFERENCES

1 +
Parry HJ, Balter MB, Mellinger GD, et al:  National patterns of psychotherapeutic drug use . Arch Gen Psychiatry 1973;;28:769-783.
2 +
Mellinger GD, Balter MB, Uhlenhuth EH:  Antianxiety agents: Duration of use and characteristics of users in the U.S.A . Curr Med Res Opin 1984;;8( (suppl 4) ):21-36.
3 +
Pflanz M, Basler HD, Schwoon D:  Use of tranquilizing drugs by a middle-aged population in a West German city . J Health Soc Behav 1977;;18:194-205.
4 +
Barsky AJ, Stewart R, Burns BJ, et al:  Neighborhood health center patients who use minor tranquilizers . Int J Addict 1979;;14:337-354.
5 +
Hemminki E:  General practitioners' indications for psychotropic drugs . Scand J Soc Med 1974;;2:79-85.
6 +
Woods JH, Katz JL, Winger GD:  Abuse liability of benzodiazepines . Pharmacol Rev 1987;;39:251-413.
7 +
National Disease and Therapeutic Index (NDTI) . Plymouth Meeting, Pa, IMS Inc, 1970-1976;.
8 +
Koch H, Campbell WH:  Utilization of psychotropic drugs in office-based ambulatory care: National ambulatory medical care survey, 1980 and 1981 . Adv Data 1983;;90:1-12.
9 +
National Prescription Audit . Plymouth Meeting, Pa, IMS America Ltd, 1970;-1976.
10 +
Rickels K, Hesbacher P:  Psychopharmacologic agents: Prescription patterns of non-psychiatrists . Psychosomatics 1977;;18:37-40.
11 +
Bush PJ, Spector KK, Rabin DL:  Use of sedatives and hypnotics prescribed in a family practice . South Med J 1984;;77:677-681.
12 +
Schuster CR, Johanson CE:  The use of animal models for the study of drug abuse , in Gibbins RJ, Israel Y, Kalant H, et al (eds): Research Advances in Alcohol and Drug Problems . New York, John Wiley & Sons Inc, 1974;, vol 1, pp 1-31.
13 +
Woods JH, Smith CB, Medzihradsky F, et al:  Preclinical testing of new analgesic drugs , in Beers RF, Bassett EG (eds): Mechanisms of Pain and Analgesic Compounds . New York, Raven Press, 1979;, pp 439-445.
14 +
Griffiths RR, Ator NA, Lukas SE, et al:  Experimental abuse liability assessment of benzodiazepines , in Usdin E, Skolnick P, Tallman JF, et al (eds): Pharmacology of Benzodiazepines . London, MacMillan Publishing Co Inc, 1982;, pp 609-618.
15 +
Johanson CE, Uhlenhuth EH:  Drug preference and mood in humans: Diazepam . Psychopharmacology 1980;;71:269-273.
16 +
De Wit H, Johanson CE, Uhlenhuth EH:  The dependence potential of benzodiazepines . Curr Med Res Opin 1984;;8:48-59.
17 +
De Wit H, Uhlenhuth EH, Johanson CE:  Lack of preference for flurazepam in normal volunteers . Pharmacol Biochem Behav 1984;;21:865-869.
18 +
De Wit H, Uhlenhuth EH, Hedeker D, et al:  Lack of preference for diazepam in anxious volunteers . Arch Gen Psychiatry 1986;;43:533-541.
19 +
Griffiths RR, Bigelow G, Liebson I:  Human drug self-administration: Double-blind comparison of pentobarbital, diazepam, chlorpromazine and placebo . J Pharmacol Exp Ther 1979;;210: 301-310.
20 +
Griffiths RR, Bigelow GE, Liebson I, et al:  Drug preference in humans: Double-blind choice comparison of pentobarbital, diazepam, and placebo . J Pharmacol Exp Ther 1980;;215:649-661.
21 +
Griffiths RR, McLeod DR, Bigelow GE, et al:  Comparison of diazepam and oxazepam: Preference, liking and extent of abuse . J Pharmacol Exp Ther 1984;;229:501-508.
22 +
Mellinger GD, Baiter MB:  Psychotherapeutic drugs: A current assessment of prevalence and patterns of use , in Morgan JP, Kagan DV (eds): Society and Medication: Conflicting Signals for Prescribers and Patients . Lexington, Ky, DC Heath & Co, 1983;, pp 137-144.
23 +
Apsler R, Rothman E:  Correlates of compliance with psychoactive prescriptions . J Psychoactive Drugs 1984;;16:193-199.
24 +
Caplan RD, Abbey A, Abramis DJ, et al: Tranquilizer Use and Well-Being: A Longitudinal Study of Social and Psychological Effects . Ann Arbor, Mich, Institute for Social Research, University of Michigan, 1984;.
25 +
Caplan RD, Andrews RM, Conway TL, et al:  Social effects of diazepam use: A longitudinal field study . Soc Sci Med 1985;;21:887-898.
26 +
Hulka BS, Cassel JC, Kupper LL, et al:  Communication, compliance, and concordance between physicians and patients with prescribed medication . Am J Public Health 1976;;66:847-853.
27 +
Balmer R, Battegay R, Von Marschall R:  Long-term treatment with diazepam: Investigation of consumption habits and the interaction between psychotherapy and psychopharmacotherapy: A prospective study . Int Pharmacopsychiatry 1981;;16:221-234.
28 +
Boethius G, Westerholm B:  Is the use of hypnotics, sedatives and minor tranquilizers really a major health problem? Acta Med Scand 1976;;17: 507-512.
29 +
Boethius G, Westerholm B:  Purchases of hypnotics, sedatives and minor tranquillizers among 2566 individuals in the county of Jamtland, Sweden: A six-year follow-up . Acta Psychiatr Scand 1977;;56:147-159.
30 +
Winstead DK, Anderson A, Eilers MK, et al:  Diazepam on demand: Drug-seeking behavior in psychiatric inpatients . Arch Gen Psychiatry 1974;;30:349-351.
31 +
Marks J: The Benzodiazepines: Use, Overuse, Misuse, Abuse , ed 2. Lancaster, England, MTP Press Ltd, 1986;.
32 +
Wolf B, Ruther E:  Drug abuse and dependence in psychiatric inpatients . Pharmacopsychiatria 1985;;18:37-39.
33 +
Ladewig D, Banziger W, Lowenheck M:  Tranquilizer abuse: Results of a nationwide Swiss survey . J Drug Res 1981;;6:1132-1137.
34 +
Schuckit MA, Morrissey ER:  Drug abuse among alcoholic women . J Psychiatry 1979;;136: 607-611.
35 +
Busto U, Sellers EM, Sisson B, et al:  Benzodiazepine use and abuse in alcoholics . Clin Pharmacol Ther 1982;;31:207-208.
36 +
Wiseman SM, Spencer-Peet J:  Prescribing for alcoholics: A survey of drugs taken prior to admission to an alcoholism unit . Practitioner 1985;;229:88-89.
37 +
Chan AWK:  Effects of combined alcohol and benzodiazepine: A review . Drug Alcohol Depend 1984;;13:315-341.
38 +
Raskind M, Bradford T:  Methylphenidate (Ritalin) abuse and methadone maintenance . Dis Nerv Syst 1975;;36:9-12.
39 +
Brown BS, Chaitkin L:  Use of stimulant/depressant drugs by drug abuse clients in selected metropolitan areas . Int J Addict 1981;;16:1473-1490.
40 +
Jauhar P:  Non-opiate abuse amongst opiate addicts , in Murray R, Ghodse H, Harris C, et al (eds): The Misuse of Psychotropic Drugs . London, Gaskell Publishers, 1981;, pp 71-73.
41 +
Tyler J, Frith GH:  Primary drug abuse among women: A national study . Drug Alcohol Depend 1981;;8:279-286.
42 +
Report of the Sixth WHO Review of Psychoactive Substances for International Control . Geneva, World Health Organization, 1982;.
43 +
Baum C, Kennedy DL, Knapp DE, et al: Drug Utilization in the U.S.—1983: Fifth Annual Review , Public Health Service publication PB85-177145. Springfield, Va, National Technical Information Service, 1985;.
44 +
Jones BE:  Predicting abuse liability of depressant drugs , in Thompson T, Unna KR (eds): Predicting Dependence Liability of Stimulant and Depressant Drugs . Baltimore, University Park Press, 1977;, pp 35-46.
45 +
Kryspin EK, Demel I:  The use of tranquilizers in the treatment of mixed drug abuse . Int J Clin Pharmacol Biopharm 1975;;12:13-18.
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Rothstein E, Cobble JC, Sampson N:  Chlordiazepoxide: Long-term use in alcoholism . Ann NY Acad Sci 1976;;273:381-384.
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Kales A, Soldatos CR, Bixler EO, et al:  Rebound insomnia and rebound anxiety: A review . Pharmacology 1983;;26:121-137.
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Woods JH, Schuster CR:  Opiates as reinforcing stimuli , in Thompson T, Pickens R (eds): Stimulus Functions of Drugs . East Norwalk, Conn, Appleton-Century-Crofts, 1971;, pp 163-175.
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97 +
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99 +
Rickels K:  Benzodiazepines in emotional disorders , in Smith DE, Wesson DR (eds): The Benzodiazepines: Current Standards for Medical Practice . Hingham, Mass, MTP Press, 1985;, pp 97-110.

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
Parry HJ, Balter MB, Mellinger GD, et al:  National patterns of psychotherapeutic drug use . Arch Gen Psychiatry 1973;;28:769-783.
2 +
Mellinger GD, Balter MB, Uhlenhuth EH:  Antianxiety agents: Duration of use and characteristics of users in the U.S.A . Curr Med Res Opin 1984;;8( (suppl 4) ):21-36.
3 +
Pflanz M, Basler HD, Schwoon D:  Use of tranquilizing drugs by a middle-aged population in a West German city . J Health Soc Behav 1977;;18:194-205.
4 +
Barsky AJ, Stewart R, Burns BJ, et al:  Neighborhood health center patients who use minor tranquilizers . Int J Addict 1979;;14:337-354.
5 +
Hemminki E:  General practitioners' indications for psychotropic drugs . Scand J Soc Med 1974;;2:79-85.
6 +
Woods JH, Katz JL, Winger GD:  Abuse liability of benzodiazepines . Pharmacol Rev 1987;;39:251-413.
7 +
National Disease and Therapeutic Index (NDTI) . Plymouth Meeting, Pa, IMS Inc, 1970-1976;.
8 +
Koch H, Campbell WH:  Utilization of psychotropic drugs in office-based ambulatory care: National ambulatory medical care survey, 1980 and 1981 . Adv Data 1983;;90:1-12.
9 +
National Prescription Audit . Plymouth Meeting, Pa, IMS America Ltd, 1970;-1976.
10 +
Rickels K, Hesbacher P:  Psychopharmacologic agents: Prescription patterns of non-psychiatrists . Psychosomatics 1977;;18:37-40.
11 +
Bush PJ, Spector KK, Rabin DL:  Use of sedatives and hypnotics prescribed in a family practice . South Med J 1984;;77:677-681.
12 +
Schuster CR, Johanson CE:  The use of animal models for the study of drug abuse , in Gibbins RJ, Israel Y, Kalant H, et al (eds): Research Advances in Alcohol and Drug Problems . New York, John Wiley & Sons Inc, 1974;, vol 1, pp 1-31.
13 +
Woods JH, Smith CB, Medzihradsky F, et al:  Preclinical testing of new analgesic drugs , in Beers RF, Bassett EG (eds): Mechanisms of Pain and Analgesic Compounds . New York, Raven Press, 1979;, pp 439-445.
14 +
Griffiths RR, Ator NA, Lukas SE, et al:  Experimental abuse liability assessment of benzodiazepines , in Usdin E, Skolnick P, Tallman JF, et al (eds): Pharmacology of Benzodiazepines . London, MacMillan Publishing Co Inc, 1982;, pp 609-618.
15 +
Johanson CE, Uhlenhuth EH:  Drug preference and mood in humans: Diazepam . Psychopharmacology 1980;;71:269-273.
16 +
De Wit H, Johanson CE, Uhlenhuth EH:  The dependence potential of benzodiazepines . Curr Med Res Opin 1984;;8:48-59.
17 +
De Wit H, Uhlenhuth EH, Johanson CE:  Lack of preference for flurazepam in normal volunteers . Pharmacol Biochem Behav 1984;;21:865-869.
18 +
De Wit H, Uhlenhuth EH, Hedeker D, et al:  Lack of preference for diazepam in anxious volunteers . Arch Gen Psychiatry 1986;;43:533-541.
19 +
Griffiths RR, Bigelow G, Liebson I:  Human drug self-administration: Double-blind comparison of pentobarbital, diazepam, chlorpromazine and placebo . J Pharmacol Exp Ther 1979;;210: 301-310.
20 +
Griffiths RR, Bigelow GE, Liebson I, et al:  Drug preference in humans: Double-blind choice comparison of pentobarbital, diazepam, and placebo . J Pharmacol Exp Ther 1980;;215:649-661.
21 +
Griffiths RR, McLeod DR, Bigelow GE, et al:  Comparison of diazepam and oxazepam: Preference, liking and extent of abuse . J Pharmacol Exp Ther 1984;;229:501-508.
22 +
Mellinger GD, Baiter MB:  Psychotherapeutic drugs: A current assessment of prevalence and patterns of use , in Morgan JP, Kagan DV (eds): Society and Medication: Conflicting Signals for Prescribers and Patients . Lexington, Ky, DC Heath & Co, 1983;, pp 137-144.
23 +
Apsler R, Rothman E:  Correlates of compliance with psychoactive prescriptions . J Psychoactive Drugs 1984;;16:193-199.
24 +
Caplan RD, Abbey A, Abramis DJ, et al: Tranquilizer Use and Well-Being: A Longitudinal Study of Social and Psychological Effects . Ann Arbor, Mich, Institute for Social Research, University of Michigan, 1984;.
25 +
Caplan RD, Andrews RM, Conway TL, et al:  Social effects of diazepam use: A longitudinal field study . Soc Sci Med 1985;;21:887-898.
26 +
Hulka BS, Cassel JC, Kupper LL, et al:  Communication, compliance, and concordance between physicians and patients with prescribed medication . Am J Public Health 1976;;66:847-853.
27 +
Balmer R, Battegay R, Von Marschall R:  Long-term treatment with diazepam: Investigation of consumption habits and the interaction between psychotherapy and psychopharmacotherapy: A prospective study . Int Pharmacopsychiatry 1981;;16:221-234.
28 +
Boethius G, Westerholm B:  Is the use of hypnotics, sedatives and minor tranquilizers really a major health problem? Acta Med Scand 1976;;17: 507-512.
29 +
Boethius G, Westerholm B:  Purchases of hypnotics, sedatives and minor tranquillizers among 2566 individuals in the county of Jamtland, Sweden: A six-year follow-up . Acta Psychiatr Scand 1977;;56:147-159.
30 +
Winstead DK, Anderson A, Eilers MK, et al:  Diazepam on demand: Drug-seeking behavior in psychiatric inpatients . Arch Gen Psychiatry 1974;;30:349-351.
31 +
Marks J: The Benzodiazepines: Use, Overuse, Misuse, Abuse , ed 2. Lancaster, England, MTP Press Ltd, 1986;.
32 +
Wolf B, Ruther E:  Drug abuse and dependence in psychiatric inpatients . Pharmacopsychiatria 1985;;18:37-39.
33 +
Ladewig D, Banziger W, Lowenheck M:  Tranquilizer abuse: Results of a nationwide Swiss survey . J Drug Res 1981;;6:1132-1137.
34 +
Schuckit MA, Morrissey ER:  Drug abuse among alcoholic women . J Psychiatry 1979;;136: 607-611.
35 +
Busto U, Sellers EM, Sisson B, et al:  Benzodiazepine use and abuse in alcoholics . Clin Pharmacol Ther 1982;;31:207-208.
36 +
Wiseman SM, Spencer-Peet J:  Prescribing for alcoholics: A survey of drugs taken prior to admission to an alcoholism unit . Practitioner 1985;;229:88-89.
37 +
Chan AWK:  Effects of combined alcohol and benzodiazepine: A review . Drug Alcohol Depend 1984;;13:315-341.
38 +
Raskind M, Bradford T:  Methylphenidate (Ritalin) abuse and methadone maintenance . Dis Nerv Syst 1975;;36:9-12.
39 +
Brown BS, Chaitkin L:  Use of stimulant/depressant drugs by drug abuse clients in selected metropolitan areas . Int J Addict 1981;;16:1473-1490.
40 +
Jauhar P:  Non-opiate abuse amongst opiate addicts , in Murray R, Ghodse H, Harris C, et al (eds): The Misuse of Psychotropic Drugs . London, Gaskell Publishers, 1981;, pp 71-73.
41 +
Tyler J, Frith GH:  Primary drug abuse among women: A national study . Drug Alcohol Depend 1981;;8:279-286.
42 +
Report of the Sixth WHO Review of Psychoactive Substances for International Control . Geneva, World Health Organization, 1982;.
43 +
Baum C, Kennedy DL, Knapp DE, et al: Drug Utilization in the U.S.—1983: Fifth Annual Review , Public Health Service publication PB85-177145. Springfield, Va, National Technical Information Service, 1985;.
44 +
Jones BE:  Predicting abuse liability of depressant drugs , in Thompson T, Unna KR (eds): Predicting Dependence Liability of Stimulant and Depressant Drugs . Baltimore, University Park Press, 1977;, pp 35-46.
45 +
Kryspin EK, Demel I:  The use of tranquilizers in the treatment of mixed drug abuse . Int J Clin Pharmacol Biopharm 1975;;12:13-18.
46 +
Rothstein E, Cobble JC, Sampson N:  Chlordiazepoxide: Long-term use in alcoholism . Ann NY Acad Sci 1976;;273:381-384.
47 +
Kales A, Soldatos CR, Bixler EO, et al:  Rebound insomnia and rebound anxiety: A review . Pharmacology 1983;;26:121-137.
48 +
Woods JH, Schuster CR:  Opiates as reinforcing stimuli , in Thompson T, Pickens R (eds): Stimulus Functions of Drugs . East Norwalk, Conn, Appleton-Century-Crofts, 1971;, pp 163-175.
49 +
Winger GD, Stitzer M, Woods JH:  Barbiturate-reinforced responding in rhesus monkeys: Comparison of drugs with different durations of actions . J Pharmacol Exp Ther 1975;;195:505-514.
50 +
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