Benzodiazepine and Other Sedative-Hypnotic Dependence

David E. Smith, M.D.; Donald R. Wesson, M.D.; Sanjay A. Sabnani



Sedative-hypnotics, including benzodiazepines, are a chemically diverse group of compounds prescribed to ameliorate symptoms of anxiety, panic disorders, and insomnia. Although differences exist among sedative-hypnotics in terms of therapeutic indications, metabolic profile, receptor affinity, side effects, and abuse potential, the benzodiazepines and newer hypnotics with similar effects at the gamma-aminobutyric acid (GABA) receptor are remarkably safe when taken in overdose. Twenty to thirty times the usual therapeutic dose is unlikely to be lethal. The "safety" of benzodiazepines in the overdose situation is an important advantage of the benzodiazepines over older sedative-hypnotics.

Your session has timed out. Please sign back in to continue.
Sign In Your Session has timed out. Please sign back in to continue.
Sign In to Access Full Content
Sign in via Athens (What is this?)
Athens is a service for single sign-on which enables access to all of an institution's subscriptions on- or off-site.
Not a subscriber?

Subscribe Now/Learn More

PsychiatryOnline subscription options offer access to the DSM-5 library, books, journals, CME, and patient resources. This all-in-one virtual library provides psychiatrists and mental health professionals with key resources for diagnosis, treatment, research, and professional development.

Need more help? PsychiatryOnline Customer Service may be reached by emailing PsychiatryOnline@psych.org or by calling 800-368-5777 (in the U.S.) or 703-907-7322 (outside the U.S.).

Table Reference Number
Table 13B–1. Characteristics of syndromes related to benzodiazepine withdrawal
Table Reference Number
Table 13B–2. Benzodiazepines and their phenobarbital withdrawal equivalents
Table Reference Number
Table 13B–3. Sedative-hypnotics and their phenobarbital withdrawal equivalents


American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision. Washington, DC, American Psychiatric Association, 2000
American Psychiatric Association Task Force on Benzodiazepine Dependency: Benzodiazepine Dependency, Toxicity, and Abuse. Washington, DC, American Psychiatric Association, 1990
Apelt S, Emrich HM: Sodium valproate in benzodiazepine withdrawal (letter). Am J Psychiatry 147:950–951, 1990
Brady KT, Sonne S, Lydiard RB: Valproate treatment of comorbid panic disorder and affective disorders in two alcoholic patients (letter). J Clin Psychopharmacol 14:81–82, 1994
Cavallaro R, Regazzetti MG, Covelli G, et al: Tolerance and withdrawal with zolpidem (letter). Lancet 342:374–375, 1993
Chutuape MA, de Wit H: Relationship between subjective effects and drug preferences: ethanol and diazepam. Drug Alcohol Depend 34:243–251, 1994
Ciraulo DA, Barnhill JG, Greenblatt DJ, et al: Abuse liability and clinical pharmacokinetics of alprazolam in alcoholic men. J Clin Psychiatry 49:333–337, 1988
Calhoun SR, Wesson DR, Galloway GP, et al: Abuse of flunitrazepam (Rohypnol) and other benzodiazepines in Austin and South Texas. J Psychoactive Drugs 28:183–189, 1996
Ernst E, Bartu A, Popescu A, et al: Methadone-related deaths in Western Australia 1993–99. Aust N Z J Public Health 26:364–370, 2002
Griffiths R, Roache J: Abuse liability of benzodiazepines: a review of human studies evaluating subjective and/or reinforcing effects, in The Benzodiazepines: Current Standards for Medical Practice. Edited by Smith D, Wesson D. Hingham, MA, MTP Press, 1985, pp 209–225
Hammer BA, Brady KT: Valproate treatment of alcohol withdrawal and mania (letter). Am J Psychiatry 153:1232, 1996
Hillbom M, Tokola R, Kuusela V, et al: Prevention of alcohol withdrawal seizures with carbamazepine and valproic acid. Alcohol 6:223–226, 1989
Hollister L, Motzenbecker E, Degan R: Withdrawal reactions from chlordiazepoxide (Librium). Psychopharmacologia 2:63–68, 1961
Hollister LE, Bennett LL, Kimbell I, et al: Diazepam in newly admitted schizophrenics. Dis Nerv Syst 24:746–750, 1963
Keck PE Jr, McElroy SL, Friedman LM: Valproate and carbamazepine in the treatment of panic and posttraumatic stress disorders, withdrawal states, and behavioral dyscontrol syndromes. J Clin Psychopharmacol 12 (suppl):36S–41S, 1992
Kintz P: Deaths involving buprenorphine: a compendium of French cases. Forensic Sci Int 121:65–69, 2001
Klein E, Uhde TW, Post RM: Preliminary evidence for the utility of carbamazepine in alprazolam withdrawal. Am J Psychiatry 143:235–236, 1986
Ladner M: History of benzodiazepine dependence. J Subst Abuse Treat 8:53–59, 1991
Lawlor BA: Carbamazepine, alprazolam withdrawal, and panic disorder (letter). Am J Psychiatry 144:265–266, 1987
McElroy SL, Keck PE Jr, Lawrence JM: Treatment of panic disorder and benzodiazepine withdrawal with valproate (letter). J Neuropsychiatry Clin Neurosci 3:232–233, 1991
Neppe VM, Sindorf J: Carbamazepine for high-dose diazepam withdrawal in opiate users. J Nerv Ment Dis 179:234–235, 1991
Richens A, Davidson DL, Cartlidge NE, et al: A multicentre comparative trial of sodium valproate and carbamazepine in adult onset epilepsy. J Neurol Neurosurg Psychiatry 57:682–687, 1994
Rickels K, Case WG, Schweizer E, et al: Benzodiazepine dependence: management of discontinuation. Psychopharmacol Bull 26:63–68, 1990a
Rickels K, Schweizer E, Case WG, et al: Long-term therapeutic use of benzodiazepines, I: effects of abrupt discontinuation [published erratum appears in Arch Gen Psychiatry 48:51, 1991]. Arch Gen Psychiatry 47:899–907, 1990b
Ries RK, Roy-Byrne PP, Ward NG, et al: Carbamazepine treatment for benzodiazepine withdrawal. Am J Psychiatry 146:536–537, 1989
Roy-Byrne PP, Ward NG, Donnelly PJ: Valproate in anxiety and withdrawal syndromes. J Clin Psychiatry 50 (suppl):44–48, 1989
Schweizer E, Rickels K, Case WG, et al: Carbamazepine treatment in patients discontinuing long-term benzodiazepine therapy: effects on withdrawal severity and outcome. Arch Gen Psychiatry 48:448–452, 1991
Smith DE, Wesson DR: A new method for treatment of barbiturate dependence. JAMA 213:294–295, 1970
Smith DE, Wesson DR: Phenobarbital technique for treatment of barbiturate dependence. Arch Gen Psychiatry 24:56–60, 1971
Smith DE, Wesson DR: Benzodiazepine dependency syndromes. J Psychoactive Drugs 15:85–95, 1983
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).
Related Content
Manual of Clinical Psychopharmacology, 7th Edition > Chapter 1.  >
Manual of Clinical Psychopharmacology, 7th Edition > Chapter 2.  >
Manual of Clinical Psychopharmacology, 7th Edition > Chapter 6.  >
Manual of Clinical Psychopharmacology, 7th Edition > Chapter 7.  >
The American Psychiatric Publishing Textbook of Psychiatry, 5th Edition > Chapter 4.  >
Psychiatric News
PubMed Articles
  • Print
  • PDF
  • E-mail
  • Chapter Alerts
  • Get Citation