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Current benzodiazepine issues

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Abstract

This article deals with some of the recent evidence bearing on the issues of the liability of benzodiazepines to lead to abuse, dependence, and adverse behavioral effects. Reviews of epidemiological, clinical and experimental literature indicated that the previous conclusion about abuse of these drugs still holds: the vast majority of the use of benzodiazepines is appropriate. Problems of nonmedical use arise nearly exclusively among people who abuse other drugs. Nevertheless, there are reasons for concern about patients who take benzodiazepines regularly for long periods of time. These drugs can produce physiological dependence when taken chronicaly, and although this does not appear to result in dose escalation or other evidence of “psychological dependence,” physiological dependence can result in patient discomfort if drug use is abruptly discontiniued. Also, physicians are currently prescribing shorter-acting benzodiazepines in preference to longer-acting benzodiazepines. The shorter-acting drugs can produce a more intense withdrawal syndrome following chronic administration. Furthermore, rates of use of benzodiazepines increase with age, and elderly patients are more likely than younger ones to take the drug chronically. The clearest adverse effect of benzodiazepines is impairment of memory. This, too, may be particular concern in older patients whose recall in the absence of drug is typically impaired relative to younger individuals, and who are more compromised following drug administration.

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References

  • Adam K, Oswald I (1989) Can a rapidly-eliminated hypnotic cause daytime anxiety? Pharmacopsychiatry 22:115–119

    Google Scholar 

  • Antonijoan RM, Barbanoj MJ, Torrent J, Jane F (1990) Evaluation of psychotropic drug consumption related to psychological distress in the elderly: hospitalized vs. nonhospitalized. Neuropsychobiology 23:25–30

    Google Scholar 

  • Ashton H (1987) Benzodiazepine withdrawal outcome in 50 patients. Br J Addict 82:665–672

    Google Scholar 

  • Balter MB (1991) Prevalence of medical use of prescription drugs. Presented at NIDA technical review, evaluation of the impact of prescription drug diversion control systems on medical practice and patient care: possible implications for future research, Bethesda, Md.

  • Bellantuono C, Arreghini E, Adami M, Bodini F, Gastaldo M, Micciolo R (1989) Psychotropic drug prescription in Italy: a survey in general practice. Soc Psychiatry Psychiatr Epidemiol 24:212–218

    Google Scholar 

  • Bliwise DL, Seidel WF, Cohen SA, Bliwise NG, Dement WC (1988) Profile of Mood States changes during and after 5 weeks of nightly triazolam administration. J Clin Psychiatry 49:349–355

    Google Scholar 

  • Busto U, Sellers EM, Naranjo CA, Cappell H, Sanchez-Craig M, Sykora K (1986) Withdrawal reaction after long-term therapeutic use of benzodiazepines. N Engl J Med 315:854–859

    Google Scholar 

  • Cantopher T, Olivieri S, Cleave N, Edwards JG (1990) Chronic benzodiazepine dependence: a comparative study of abrupt withdrawal under propranolol cover versus gradual withdrawal. Br J Psychiatry 156:406–411

    Google Scholar 

  • Cappell H, Busto U, Kay G, Naranjo CA, Sellers EM, Sanchez-Craig M (1987) Drug deprivation and reinforcement by diazepam in a dependent population. Psychopharmacology 91:154–160

    Google Scholar 

  • Consensus conference (1984) Drugs and insomnia: the use of medications to promote sleep. JAMA 351:2410–2414

    Google Scholar 

  • Coryell W, Noyes R, Clancy J (1982) Excess mortality in panic disorder: a comparison with primary unipolar depression. Arch Gen Psychiatry 39:701–703

    Google Scholar 

  • Cumming RG, Miller JP, Kelsey JL, Davis P, Arfken CL, Birge SJ and Peck WA (1991) Medications and multiple falls in elderly people:the St. Louis OASIS Study. Age Ageing 20:455–461

    Google Scholar 

  • DeWit H, Pierri J, Johanson CE (1989) Reinforcing and subjective effects of diazepam in nondrug-abusing volunteers. Pharmacol Biochem Behav 33:205–213

    Google Scholar 

  • Eadie JL (1990) Policy concerns: benzodiazepine abuse and misuse: New York state's response. In: Wilford BB (ed) Balancing the response to prescription drug abuse. American Medical Association, Chicago, Ill., pp 93–102

    Google Scholar 

  • Fawcett J (1988) Predictors of early suicide: identification and appropriate intervention. J Clin Psychiatry 49[suppl]:7–8

    Google Scholar 

  • Fichter MM, Witzke W, Leibl K, Hippius H (1989) Psychotropic drug use in a representative community sample: the Upper Bavarian West Germany study. Acta Psychiatr Scand 80:68–77

    Google Scholar 

  • Fyer AJ, Liebowitz MR, Gorman JM, Campeas R, Levin A, Davies SO, Goetz D and Klein DF (1987) Discontinuation of alprazolam treatment in panic patients. Am J Psychiatry 144:303–308

    Google Scholar 

  • Gallager DW, Heninger K, Heninger G (1986) Periodic benzodiazepine antagonist administration prevents benzodiazepine withdrawal symptoms in primates. Eur J Pharmacol 132:31–38

    Google Scholar 

  • Geneé-Badia J, Blay-Pueyo C, Soler-Vila M (1988) Risk factors in the use of benzodiazepines. Fam Pract. 5:283–288

    Google Scholar 

  • Golenpaul D (1991) The 1991 Information Please Almanac, 15th Ed., Boston, MA: Houghton Mifflin, 1991:141

    Google Scholar 

  • Golombok S, Higgitt A, Fonagy P, Dodds S, Saper J, Lader M (1987) A follow-up study of patients treated for benzodiazepine dependence. Br J Med Psychol 60:141–150

    Google Scholar 

  • Greenblatt DJ, Shade RI, Harmatz JS (1989) Implications of altered drug disposition in the elderly: studies of benzodiazepines. J Clin Pharmacology 29:866–872

    Google Scholar 

  • Greenblatt DJ, Jerold SH, Shapiro L, Engelhardt N, Gouthro TA, Shader RI (1991) Sensitivity to triazolam in the elderly. N Engl J Med 324:1691–1698

    Google Scholar 

  • Grisso JA, Kelsey JL, Strom BL, Chiu GY, Maislin G, O'Brien LA, Hoffman S, Kaplan F (1991) Risk factors for falls as a cause of hip fracture in women. N Engl J Med 324:1326–1331

    Google Scholar 

  • Gurwitz JH, Avorn J (1991) The ambiguous relation between aging and adverse drug reactions. Ann Int Medicine 114:956–966

    Google Scholar 

  • Hale WE, Stewart RB, Marks RG (1985) Anti-anxiety drugs and central nervous system symptoms in an ambulatory elderly population. DICP 19:37–40

    Google Scholar 

  • Haskell D, Cole JO, Schniebolk S, Lieberman B (1986) A survey of diazepam patients. Psychopharmacol Bull 22:434–438

    Google Scholar 

  • Higgitt AC, Lader MH, Fonagy P (1985) Clinical management of benzodiazepine dependence. BMJ 291:688–690

    Google Scholar 

  • Hinrichs JV, Ghoneim MM (1987) Diazepam, behavior, and aging: increased sensitivity or lower baseline performance? Psychopharmacology 92:100–105

    Google Scholar 

  • Hoffman RS, Wipfler JG, Maddaloni MA, Weisman RS (1991) Has the New York State triplicate benzodiazepine prescription regulation influence sedative-hypnotic overdoses? N Y State J Med 91:436–439

    Google Scholar 

  • Holton A, Tyrer P (1990) Five year outcome in patients withdrawn from long term treatment with diazepam. BMJ 300:1241–1242

    Google Scholar 

  • Johnston LD, O'Malley PM, Bachman JG (1993a) National Survey Results on Drug Use from the Monitoring the Future Study, 1975–1992: Volume I: Secondary School Students. NIH Publication No. 93-3597. Washington: U.S. Government Printing Office

    Google Scholar 

  • Joughin N, Tata P, Collins M, Hooper C, Falkowski J (1991) Impatient withdrawal from long-term benzodiazepine use. Br J Addict 86:449–455

    Google Scholar 

  • IMS America Ltd. National Disease and Therapeutic Index (NDTI), Plymouth Meeting, PA: IMS America, Ltd; 1991

    Google Scholar 

  • Kales A, Soldatos CR, Bixler EO, Kales JD (1983) Early morning insomnia with rapidly eliminated benzodiazepines. Science 220:95–97

    Google Scholar 

  • Lesser IM, Rubin RT, Pecknold JC, Rifkin A, Swinson RP, Lydiard RB, Burrows GD, Noyes R, Dupont RL (1988) Secondary depression in panic disorder and agoraphobia. I. Frequency, severity, and response to treatment. Arch Gen Psychiatry 45:437–443

    Google Scholar 

  • Lucki I, Rickels K (1988) The effect of anxiolytic drugs on memory in anxious subjects. Psychopharmacol Ser 6:128–139

    Google Scholar 

  • Lucki I, Volpicelli JR, Schweizer E (1991) Differential craving between abstinent alcohol-dependent subjects and therapeutic users of benzodiazepines. NIDA Res Monogr 105:322–323

    Google Scholar 

  • Magni G, Schifano F, Pastorello M, Deleo D, DeDominicis MG (1986) Use of psychotropic drugs in general, medical geriatric inpatients: relationship with various parameters of psychological distress evluated in blind. Neuropsychobiology. 16:181–185

    Google Scholar 

  • Mamelak M, Csima A, Price V (1984) A comparative 25-night sleep laboratory study on the effects of quazepam and triazolam on chronic insomniacs. J Clin Pharmacol 24:65–75

    Google Scholar 

  • Mellinger GD, Balter MB, Manheimer DI, Cisin IH, Parry HJ (1978) Psychic distress, life crisis, and use of psychotherapeutic medications: National Household Survey data. Arch Gen Psychiatry 35:1045

    Google Scholar 

  • Mellinger GD, Balter MB, Uhlenhuth EH (1984a) Anti-anxiety agents: duration of use and characteristics of users in the U.S.A. Curr Med Res Opin 8 (suppl. 4):21–36

    Google Scholar 

  • Mellinger GD, Balter MB, Uhlenhuth EH (1984b) Prevalence and correlates of the long term regular use of anxiolytics. JAMA 331:375–379

    Google Scholar 

  • Mellman TA, Uhde TW (1986) Withdrawal syndrome with gradual tapering of alprazolam. Am J Psychiatry 143:1464–1466

    Google Scholar 

  • Morgan K, Oswald I (1982) Anxiety caused by a short-life hypnotic. Br Med J 284:942

    Google Scholar 

  • Murphy SM, Owen R, Tyrer P (1989) Comparative assessment of efficacy and withdrawal symptoms after 6 and 12 weeks' treatment with diazepam or buspirone. Br J Psychiatry 154:529–534

    Google Scholar 

  • Myers AH, Baker SP, Van Natta ML, Abbey H, Robinson EG (1991) Risk factors associated with falls and injuries among elderly institutionalized persons. Am J Epidemiol 133:1179–1190

    Google Scholar 

  • Noyes R, Garvey MJ, Cook B, Suelzer M (1991) Controlled discontinuation of benzodiazepine treatment for patients with panic disorder. Am J Psychiatry 148:517–523

    Google Scholar 

  • Orsini A, Brancato V, Smeraldi E (1990) Length of anxiolytic treatment and benzodiazepine withdrawal symptoms: a double blind study with clotiazepam. New Trends Exp Clin Psychiatry 6:45–52

    Google Scholar 

  • Oster G, Russell MW, Huse DM, Adams SF, Imbimbo J (1987) Accident and injury related health care utilization among benzodiazepine users and nonusers. J Clin Psychiatry 48:17–21

    Google Scholar 

  • Oster G, Huse DM, Adams SF, Imbimbo J, Russell MW (1990) Benzodiazepine tranquilizers and the risk of accidental injury. Am J Public Health 80:1467–1470

    Google Scholar 

  • Pakesch G, Loimer N, Rasinger E, Tutsch G, Katschnig H (1989) The prevalence of psychoactive drug intake in a metropolitan population. Pharmacopsychiatry 2:61–65

    Google Scholar 

  • Pecknold JC, Swinson RP, Kuch K, Lewis CP (1988) Alprazolam in panic disorder and agoraphobia: results from a multicenter trial. III. Discontinuation effects. Arch Gen Psychiatry 45:429–436

    Google Scholar 

  • Pomara N, Deptula D, Medel M, Block RI, Greenblatt DJ (1989) Effects of diazepam on recall memory: relationship to aging, dose, and duration of treatment. Psychopharmacol Bull 25:144–148

    Google Scholar 

  • Priebe S, Liesenfeld O, Muller-Oerlinghausen B (1988) Resumption of benzodiazepine use after withdrawal in hospital — a follow-up study. Pharmacopsychiatry 21:353–354

    Google Scholar 

  • Ray WA, Griffin MR, Schaffner W, Baugh DK, Melton LJ (1987) Psychotropic drug use and the risk of hip fracture. N Engl J Med 316:363–369

    Google Scholar 

  • Ray WA, Griffin MR, Downey W (1989) Benzodiazepines of long and short elimination half-life and the risk of hip fracture. JAMA 262:3303–3307

    Google Scholar 

  • Ray, WA (1992) Psychotropic drugs and injuries among the elderly: a review. J Clin Psychopharmacology 12:386–396

    Google Scholar 

  • Regis DA, Boyd JH, Burke JD, Rae DS, Myers JK, Kramer M, Robins LN, George LK, Karno M and Lock BZ (1988) One-month prevalence of mental disorders in the United States: based on five epidemiologic catchment area sites. Arch Gen Psychiatry 45:977–986

    Google Scholar 

  • Reidenburg MM (1991) Effect of the requirement for triplicate prescriptions for benzodiazepines in New York State. Clin Pharmacol Ther 50:129–131

    Google Scholar 

  • Rickels K, Case WG, Schweizer EE, Swenson C, Fridman RB (1986) Low-dose dependence in chronic benzodiazepine users: a preliminary report of 119 patients. Psychopharmacol Bull 22:407

    Google Scholar 

  • Rickels K, Fox IL, Greenblatt DJ, Sandler KR, Schless A (1988) Clorazepate and lorazepam: clinical improvement and rebound anxiety. Am J Psychiatry 145:312–317

    Google Scholar 

  • Rickels K, Schweizer E, Cse WG, Greenblatt DJ (1990) Long-term therapeutic use of benzodiazepines. I. Effects of abrupt discontinuation. Arch Gen Psychiatry 47:899–907

    Google Scholar 

  • Rickels K, Case W, Schweizer E, Garcia-Espana F, Fridman R (1991) Long-term benzodiazepine users 3 years after participation in a discontinuation program. Am J Psychiatry 148:757–761

    Google Scholar 

  • Ried LD, Christensen DB, Stergachis A (1990) Medical and psychosocial factors predictive of psychotropic drug use in elderly patients. Am J Public Health 80:1349–1353

    Google Scholar 

  • Roth T, Kramer M, Lutz T (1976) Intermediate use of triazolam: a sleep laboratory study. J Int Med Res 4:59–63

    Google Scholar 

  • Salinsky JV, Dore CJ (1987) Characteristics of long term benzodiazepine users in general practice. J R Coll Gen Pract 37:202–204

    Google Scholar 

  • Schwartz HI, Blank K (1991) Regulation of benzodiazepine prescribing practices: clinical implications. Gen Hosp Psychiatry 13:219–224

    Google Scholar 

  • Schweizer E, Case WE, Rickels K (1989) Benzodiazepine dependence and withdrawal in elderly patients. Am J Psychiatry 146:529–531

    Google Scholar 

  • Schweizer E, Rickels K, Case WG, Greenblatt DJ (1990) Long term therapeutic use of benzodiazepines. II. Effects of gradual taper. Arch Gen Psychiatry 47:908–915

    Google Scholar 

  • Shader RI, Greenblatt DJ, Balter MB (1991) Appropriate use and regulatory control of benzodiazepines. J Clin Pharmaco 31:781–784

    Google Scholar 

  • Sobel KG, McCart GM (1983) Drug use and accidental falls in an intermediate care facility. DICP 17:539–542

    Google Scholar 

  • Sorock GS, Shimkin EE (1988) Benzodiazepine sedatives and the risk of falling in a community-dwelling elderly cohort. Arch Intern Med 148:2441–2444

    Google Scholar 

  • Substance Abuse and Mental Health Services Administration (1993) National Household Survey on Drug Abuse: Main Findings 1991. Revised November 20, 1992. DHHS Publication No. (SMA) 93-1980. Washington: U.S. Government Printing Office

    Google Scholar 

  • Substance Abuse and Mental Health Services Administration (1993) National Household Survey on Drug Abuse: Population Estimates 1992. DHHS Publication No. (SMA) 93-2053. Washington: U.S. Government Printing Office

    Google Scholar 

  • Swartz M, Landerman R, George LK, Melviller ML, Blazer D, Smith K (1991) Benzodiazepine anti-anxiety agents: prevalence and correlates of use in a southern community. Am J Public Health. 81:592–596

    Google Scholar 

  • Trewin VF, Lawrence CJ, Veitch GB (1992) An investigation of the association of benzodiazepines and other hypnotics with the incidence of falls in the elderly. J Clin Pharm Ther 17:129–133

    Google Scholar 

  • Vazquez-Barquero JL, Diez-Manrique JF, Pena C, Arenal-Gonzalez A, Cuesta MJ, Artal JA (1989) Patterns of psychotropic drug use in a Spanish rural community. Br J Psychiatry 155:633–641

    Google Scholar 

  • Weintraub M, Singh S, Byrne L, Maharaj K, Guttmacher L (1991) Consequences of the 1989 New York State triplicate benzodiazepine prescription regulations. JAMA 266:2392–2433

    Google Scholar 

  • Wells BG, Middleton B, Lawrence G, Lillard D, Safarik J (1985) Factors associated with the elderly falling in intermediate care facilities. DICP 19:142–145

    Google Scholar 

  • Woods JH, Katz JL, Winger G (1987) Abuse liability of benzodiazepines. Pharmacol Rev. 39:251–419

    Google Scholar 

  • Woods JH, Katz JL, Winger G (1988) Use and abuse of benzodiazepines: issues relevant to prescribing. JAMA 26:3476–3480

    Google Scholar 

  • Woods JH (1990) Abuse liability and the regulatory control of therapeutic drugs: untested assumptions. Drug Alcohol Depend 25:229–233

    Google Scholar 

  • Woods JH, Katz JL, Winger G (1992) Benzodiazepines: use, abuse, and consequences. Pharmacol Rev 44:151–347

    Google Scholar 

  • Zullich SG, Grasela TH, Fieldler-Kelly JB, Gengo FM (1992) Impact of triplicate prescription program on psychotropic prescribing patterns in long-term care facilities. Annals of Pharmacotherapy 26:539–546

    Google Scholar 

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This article was supported by USPHS Grant DA-00254 and by funding from Hoffmann-La Roche, Inc.

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Woods, J.H., Winger, G. Current benzodiazepine issues. Psychopharmacology 118, 107–115 (1995). https://doi.org/10.1007/BF02245824

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