Benzodiazepine Dependence
Abstract
Summary: Benzodiazepines, the most widely used of all drugs, are powerful anxiolytics, anticonvulsants and muscle relaxants. Dependence is difficult to induce in animals but has been induced by high doses in man. Case reports of benzodiazepine dependence are rare compared with the usage of these drugs, but do not provide a proper epidemiological framework for the estimation of risk. Patients taking these drugs for four months or more may develop a physical withdrawal syndrome, characterized by anxiety, dysphoria, malaise, depersonalization, and by perceptual changes such as hyperacusis and unsteadiness. In our experience drawn from over 20 patients, withdrawal from therapeutic doses of a benzodiazepine may be attended by a fully‐developed physical withdrawal syndrome.
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Zolpidem withdrawal seizure has been described in two cases across three reports.
“(3) three reports of 2 cases of zolpidem withdrawal seizure were described [34, 35]”
From Acute and Persistent Withdrawal Syndromes Following Discontinuation of Psychotropic Medications (2020) · cites this paper as [35]
Cites
The effects of age and liver disease on the disposition and elimination of diazepam in adult man.
Klotz, U. E., Avant, G. R., Hoyumpa, A. M., Schenker, S., & Wilkinson, G. R. (1975) · Journal of Clinical Investigation · doi:10.1172/jci107938 · Cited by 693 · see citing works
Psychiatric Illness in General Practice.
Kaufman, M. R. (1967) · Archives of General Psychiatry · doi:10.1001/archpsyc.1967.01730210127023 · Cited by 590 · see citing works
Withdrawal reactions from chlordiazepoxide (?Librium?)
Hollister, L. E., Motzenbecker, F. P., & Degan, R. O. (1961) · Psychopharmacologia · doi:10.1007/bf00429621 · Cited by 340 · see citing works
Kaplan, S. A., Jack, M. L., Alexander, K., & Weinfeld, R. E. (1973) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.2600621111 · Cited by 260 · see citing works
Dependence, Tolerance, and Addiction to Benzodiazepines: Clinical and Pharmacokinetic Considerations
Greenblatt, D. J., & Shader, R. I. (1978) · Drug Metabolism Reviews · doi:10.3109/03602537808993775 · Cited by 230 · see citing works
Phobic Anxiety Syndrome Complicated by Drug Dependence and Addiction
Quitkin, F. M. (1972) · Archives of General Psychiatry · doi:10.1001/archpsyc.1972.01750260013002 · Cited by 227 · see citing works
Cross-National Study of the Extent of Anti-Anxiety/Sedative Drug Use
Balter, M. B., Levine, J., & Manheimer, D. I. (1974) · New England Journal of Medicine · doi:10.1056/nejm197404042901404 · Cited by 226 · see citing works
Use of medicines in general practice.
Skegg, D. C. G., Doll, R., & Perry, J. M. (1977) · BMJ · doi:10.1136/bmj.1.6076.1561 · Cited by 211 · see citing works
Benzodiazepines in Clinical Practice
ASCINO, F. J. M. (1975) · American Journal of Psychiatry · doi:10.1176/ajp.132.2.206-a · Cited by 196 · see citing works
the Boston Collaborative Drug Surveillance Program, B. U. M. C. (1973) · New England Journal of Medicine · doi:10.1056/nejm197302082880602 · Cited by 196 · see citing works
Pharmacokinetics of diazepam following multiple-dose oral administration to healthy human subjects
Eatman, F. B., Colburn, W. A., Boxenbaum, H. G., et al. (1977) · Journal of Pharmacokinetics and Biopharmaceutics · doi:10.1007/bf01061729 · Cited by 169 · see citing works
LENGTH OF TREATMENT WITH ANXIOLYTIC SEDATIVES AND RESPONSE TO THEIR SUDDEN WITHDRAWAL
Covi, L., Lipman, R. S., Pattison, J. H., Derogatis, L. R., & Uhlenhuth, E. H. (1973) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.1973.tb04398.x · Cited by 162 · see citing works
(1964) · The Lancet · doi:10.1016/s0140-6736(64)93056-9 · Cited by 161 · see citing works
Withdrawal symptoms in neonates from intrauterine exposure to diazepam
Rementería, J. L., & Bhatt, K. (1977) · The Journal of Pediatrics · doi:10.1016/s0022-3476(77)80785-3 · Cited by 160 · see citing works
Withdrawal Reaction From Long-term, Low-dosage Administration of Diazepam
Winokur, A. (1980) · Archives of General Psychiatry · doi:10.1001/archpsyc.1980.01780140103012 · Cited by 156 · see citing works
Valzelli, L. (1967) · Advances in pharmacology · doi:10.1016/s1054-3589(08)60655-9 · Cited by 153 · see citing works
DEPENDENCE LIABILITY OF SEVERAL SEDATIVE-HYPNOTIC AGENTS EVALUATED IN MONKEYS
Yanagita, T., & Takahashi, S. (1973) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)29510-6 · Cited by 145 · see citing works
Möhler, H., Okada, T., & Enna, S. J. (1978) · Brain Research · doi:10.1016/0006-8993(78)90526-7 · Cited by 145 · see citing works
Manual of Psychiatric Therapeutics
Edwards, G. (1976) · BMJ · doi:10.1136/bmj.2.6027.117-b · Cited by 128 · see citing works
Hospital Admissions Due to Adverse Drug Reactions
Miller, R. R. (1974) · Archives of Internal Medicine · doi:10.1001/archinte.1974.00320200029002 · Cited by 127 · see citing works
Self-poisoning with Drugs: A Worsening Situation
Smith, A. J. (1972) · BMJ · doi:10.1136/bmj.4.5833.157 · Cited by 110 · see citing works
Chlordiazepoxide loses its anxiolytic action with long-term treatment
Vellucci, S. V., & File, S. E. (1979) · Psychopharmacology · doi:10.1007/bf00426036 · Cited by 106 · see citing works
Benzodiazepines—the opium of the masses?
Lader, M. H. (1978) · Neuroscience · doi:10.1016/0306-4522(78)90098-2 · Cited by 95 · see citing works
Self-citationMisuse and Abuse of Diazepam: An Increasingly Common Medical Problem
WOODY, G. E., O’Brien, C. P., & Greenstein, R. A. (1975) · International Journal of the Addictions · doi:10.3109/10826087509027342 · Cited by 95 · see citing works
Rapid Recovery From Massive Diazepam Overdose
Greenblatt, D. J. (1978) · JAMA · doi:10.1001/jama.1978.03290170054026 · Cited by 93 · see citing works
Abrupt Withdrawal From Therapeutically Administered Diazepam
Pevnick, J. S. (1978) · Archives of General Psychiatry · doi:10.1001/archpsyc.1978.01770320089008 · Cited by 91 · see citing works
Antianxiety Drugs and Human Performance
McNair, D. M. (1973) · Archives of General Psychiatry · doi:10.1001/archpsyc.1973.04200050024004 · Cited by 91 · see citing works
Benzodiazepines and Withdrawal Psychosis
Preskorn, S. (1977) · JAMA · doi:10.1001/jama.1977.03270280038018 · Cited by 87 · see citing works
The Benzodiazepines: Use, Overuse, Misuse, Abuse
Ingram, I. M. (1978) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.41.12.1151-a · Cited by 81 · see citing works
Findley, J. D., Robinson, W. W., & Peregrino, L. (1972) · Psychopharmacology · doi:10.1007/bf00422097 · Cited by 79 · see citing works
WITHDRAWAL PSYCHOSIS: A STUDY OF 30 CONSECUTIVE CASES
Fruensgaard, K. (1976) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.1976.tb00065.x · Cited by 75 · see citing works
Chlordiazepoxide withdrawal in the neonate
Athinarayanan, P., Pierog, S. H., Nigam, S., & Glass, L. (1976) · American Journal of Obstetrics and Gynecology · doi:10.1016/s0002-9378(16)33306-3 · Cited by 71 · see citing works
Diazepam actions and plasma concentrations following ethanol ingestion
MacLeod, S. M., Giles, H. G., Patzalek, G., et al. (1977) · European Journal of Clinical Pharmacology · doi:10.1007/bf00566531 · Cited by 71 · see citing works
Comparison of the pharmacokinetics of diazepam after single and subchronic doses
Klotz, U. E., Antonin, K. H., & Bieck, P. R. (1976) · European Journal of Clinical Pharmacology · doi:10.1007/bf00609470 · Cited by 70 · see citing works
Maletzky, B. M., & Klotter, J. (1976) · International Journal of the Addictions · doi:10.3109/10826087109045533 · Cited by 68 · see citing works
Kanto, J., Iisalo, E., Lehtinen, V., & Salminen, J. J. (1974) · Psychopharmacology · doi:10.1007/bf00421784 · Cited by 66 · see citing works
Bliding, �. (1974) · European Journal of Clinical Pharmacology · doi:10.1007/bf00560382 · Cited by 59 · see citing works
PLASMA DIAZEPAM CONCENTRATIONS FOLLOWING PROLONGED ADMINISTRATION
GAMBLE, J. A. S., Dundee, J. W., & Gray, R. C. (1976) · British Journal of Anaesthesia · doi:10.1093/bja/48.11.1087 · Cited by 56 · see citing works
Diazepam withdrawal syndrome: a case with psychosis, seizure, and coma
Bard, M. L. D. (1979) · American Journal of Psychiatry · doi:10.1176/ajp.136.1.104 · Cited by 52 · see citing works
TOXIC PSYCHOSIS WITH TRANSIENT DYSMNESTIC SYNDROME FOLLOWING WITHDRAWAL FROM VALIUM
Barten, H. H. (1965) · American Journal of Psychiatry · doi:10.1176/ajp.121.12.1210 · Cited by 46 · see citing works
Development of morphine dependence in rats: Lack of effect of previous ingestion of other drugs
Stolerman, I. P., Kumar, R. C., & Steinberg, H. (1971) · Psychopharmacology · doi:10.1007/bf00403564 · Cited by 44 · see citing works
Heisterkamp, D. V., & Cohen, P. J. (1975) · British Journal of Anaesthesia · doi:10.1093/bja/47.1.79 · Cited by 44 · see citing works
Winstead, D. K. (1974) · Archives of General Psychiatry · doi:10.1001/archpsyc.1974.01760090059010 · Cited by 43 · see citing works
Diazepam withdrawal psychosis: a case report
Dysken, M. W., & Chan, C. H. (1977) · American Journal of Psychiatry · doi:10.1176/ajp.134.5.573 · Cited by 40 · see citing works
Physiological and psychological effects of clorazepate in man.
Lader, M. H., Curry, S. H., & Baker, W. (1980) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.1980.tb04801.x · Cited by 37 · see citing works
Self-citationAssisted Covert Sensitization for Drug Abuse
Maletzky, B. M. (1974) · International Journal of the Addictions · doi:10.3109/10826087409057361 · Cited by 36 · see citing works
Drug abuse: Social and Psychopharmacological Aspects
(1970) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.2600590544 · Cited by 35 · see citing works
Dependence on sedative and hypnotic drugs. A comparative clinical and social study.
Allgulander, C. (1978) · PubMed · Cited by 32 · see citing works
Letter: Diazepam withdrawal fits.
Vyas, I., & Carney, M. W. P. (1975) · BMJ · doi:10.1136/bmj.4.5987.44-a · Cited by 31 · see citing works
Bræstrup, C., & Nielsen, M. B. (1985) · Clinical Neuropharmacology · doi:10.1097/00002826-198508001-00002 · Cited by 31 · see citing works
Antianxiety Drugs: Clinical use in Psychiatry
Rickels, K., Downing, R. W., & Winokur, A. (1978) · Springer eBooks · doi:10.1007/978-1-4684-3189-6_7 · Cited by 30 · see citing works
A Case of Oxazepam (Serenid D) Dependence
Hanna, S. M. (1972) · The British Journal of Psychiatry · doi:10.1192/bjp.120.557.443 · Cited by 30 · see citing works
Diazepam, alcohol, and barbiturate abuse.
Clare, A. W. (1971) · BMJ · doi:10.1136/bmj.4.5783.340 · Cited by 30 · see citing works
Incidence in a University Hospital Psychiatric Ward
Bakewell, W. E. (1966) · JAMA · doi:10.1001/jama.1966.03100210080021 · Cited by 28 · see citing works
Drug-taking in delinquent boys.
Noble, P. J. (1970) · BMJ · doi:10.1136/bmj.1.5688.102 · Cited by 28 · see citing works
Induction Effect of Diazepam on its Own Metabolism
Sellman, R., Kanto, J., Raijola, E., et al. (1975) · Acta Pharmacologica et Toxicologica · doi:10.1111/j.1600-0773.1975.tb00852.x · Cited by 26 · see citing works
Self administration of minor tranquilizers as a function of conditioning
Harris, R. T., Claghorn, J. L., & Schoolar, J. C. (1968) · Psychopharmacology · doi:10.1007/bf00401621 · Cited by 23 · see citing works
Rastogi, R. B., Lapierre, Y. D., & Singhal, R. L. (1978) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/y78-123 · Cited by 23 · see citing works
Addiction to Diazepam (Valium)
Gordon, E. (1967) · BMJ · doi:10.1136/bmj.1.5532.112 · Cited by 22 · see citing works
Greenblatt, D. J., Shader, R. I., Harmatz, J. S., et al. (1979) · Psychopharmacology · doi:10.1007/bf00428321 · Cited by 21 · see citing works
CLINICAL EVALUATION OF DIAZEPAM.
Gh, A. (1964) · PubMed · Cited by 21 · see citing works
Morgan, H. G., Boulnois, J., & Burns‐Cox, C. J. (1973) · BMJ · doi:10.1136/bmj.2.5858.93 · Cited by 20 · see citing works
Deneau, G. A., & Weiss, S. (1968) · Pharmacopsychiatry · doi:10.1055/s-0028-1094225 · Cited by 20 · see citing works
Se, S., & Hamilton, R. G. (1966) · PubMed · Cited by 20 · see citing works
Letter: Diazepam withdrawal symptoms.
Bant, W. (1975) · BMJ · doi:10.1136/bmj.4.5991.285-b · Cited by 18 · see citing works
Hallucinations following withdrawal of Valium.
Jb, F., & Cm, M. (1976) · PubMed · Cited by 18 · see citing works
Effects of Chronic Prazepam Administration on Drug Metabolism in Man and Rat
Vesell, E. S., Passananti, G. T., Viau, J., et al. (2008) · Pharmacology · doi:10.1159/000136289 · Cited by 17 · see citing works
MISSBRAUCH VON BENZODIAZEPINDERIVATEN BEI ALKOHOLKRANKEN*
Kryspin-Exner, K. (1966) · British Journal of Addiction to Alcohol & Other Drugs · doi:10.1111/j.1360-0443.1966.tb04941.x · Cited by 17 · see citing works
Nitrazepam (Mogadon) Dependence
Misra, P. G. (1975) · The British Journal of Psychiatry · doi:10.1192/bjp.126.1.81 · Cited by 17 · see citing works
Case report: A Delirious Abstinence Syndrome associated with Clorazepate (TranxilenR)
Allgulander, C., & Borg, S. (1978) · British Journal of Addiction to Alcohol & Other Drugs · doi:10.1111/j.1360-0443.1978.tb00139.x · Cited by 16 · see citing works
Death following withdrawal of Diazepam.
Relkin, R. (1966) · PubMed · Cited by 16 · see citing works
KORSAKOFF-LIKE PSYCHOSIS ASSOCIATED WITH BENZODIAZEPINE OVERDOSAGE
HALLBERG, R. J., LESSLER, K., & Kane, F. J. (1964) · American Journal of Psychiatry · doi:10.1176/ajp.121.2.188 · Cited by 15 · see citing works
Withdrawal reaction to diazepam
Rifkin, A. (1976) · JAMA · doi:10.1001/jama.236.19.2172b · Cited by 14 · see citing works
RAPID HABITUATION TO CHLORDIAZEPOXIDE (“LIBRIUM”)
Guile, L. A. (1963) · The Medical Journal of Australia · doi:10.5694/j.1326-5377.1963.tb24611.x · Cited by 13 · see citing works
Suspected dependence on chlordiazepoxide hydrochloride (Librium).
Slater, J. D. (1966) · PubMed · Cited by 12 · see citing works
DELIRIUM TREMENS FOLLOWING WITHDRAWAL OF NITRAZEPAM
Darcy, L. (1972) · The Medical Journal of Australia · doi:10.5694/j.1326-5377.1972.tb47398.x · Cited by 11 · see citing works
The Role of Diazepam (Valium) In Emotional Illness
Bowes, H. A. (1965) · Psychosomatics · doi:10.1016/s0033-3182(65)72251-2 · Cited by 9 · see citing works
A possible oxazepam abstinence syndrome
Selig, J. W. (1966) · JAMA · doi:10.1001/jama.198.8.951 · Cited by 9 · see citing works
The Dangers of Diazepam, a Street Drug
(1974) · New England Journal of Medicine · doi:10.1056/nejm197404042901417 · Cited by 8 · see citing works
Kellett, J. M. (1974) · The Lancet · doi:10.1016/s0140-6736(74)91183-0 · Cited by 7 · see citing works
Response to Librium in individuals with a propensity for addiction: a pilot study.
Gw, B., & Cw, A. (1962) · PubMed · Cited by 7 · see citing works
Drug habituation in an urban general practice.
Grant, I. N. (1969) · PubMed · Cited by 7 · see citing works
FOUR CASES OF PROGRESSIVE DRUG ABUSE
Bartholomew, A. A., & Reynolds, W. M. (1967) · The Medical Journal of Australia · doi:10.5694/j.1326-5377.1967.tb21535.x · Cited by 6 · see citing works
Temporal Lobe Epilepsy due to Drug Withdrawal
Malcolm, M. T. (1972) · British Journal of Addiction to Alcohol & Other Drugs · doi:10.1111/j.1360-0443.1972.tb01212.x · Cited by 5 · see citing works
Fevre, C. G. L. (1971) · The Medical Journal of Australia · doi:10.5694/j.1326-5377.1971.tb87595.x · Cited by 4 · see citing works
Septic retinitis due to injection of a homemade alcoholic beverage
Eichner, H. L. (1970) · JAMA · doi:10.1001/jama.213.10.1644 · Cited by 2 · see citing works
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Guidelines for the Rational Use of Benzodiazepines: When and What to Use
Ashton, H. (1994) · Drugs · doi:10.2165/00003495-199448010-00004 · Cited by 593 · see citing works
The diagnosis and management of benzodiazepine dependence
Ashton, H. (2005) · Current Opinion in Psychiatry · doi:10.1097/01.yco.0000165594.60434.84 · Cited by 455 · see citing works
Withdrawal from long-term benzodiazepine treatment
Petursson, H., & Lader, M. H. (1981) · BMJ · doi:10.1136/bmj.283.6292.643 · Cited by 367 · see citing works
Self-citationAcute and Persistent Withdrawal Syndromes Following Discontinuation of Psychotropic Medications
Cosci, F., & Chouinard, G. (2020) · Psychotherapy and Psychosomatics · doi:10.1159/000506868 · Cited by 265 · see citing works
Tolerance to the behavioral actions of benzodiazepines
File, S. E. (1985) · Neuroscience & Biobehavioral Reviews · doi:10.1016/0149-7634(85)90037-5 · Cited by 205 · see citing works
Protracted withdrawal syndromes from benzodiazepines
Ashton, H. (1991) · Journal of Substance Abuse Treatment · doi:10.1016/0740-5472(91)90023-4 · Cited by 170 · see citing works
Polymedication and medication compliance in patients with chronic non-malignant pain
Berndt, S., Maier, C., & Schütz, H.-W. (1993) · Pain · doi:10.1016/0304-3959(93)90167-n · Cited by 112 · see citing works
Cantopher, T., Olivieri, S., Cleave, N., & Edwards, J. G. (1990) · British Journal of Psychiatry · doi:10.1192/bjp.156.3.406 · Cited by 67 · see citing works
Cheng, T., Wallace, D. M., Ponteri, B. B., & Tuli, M. (2018) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s164307 · Cited by 66 · see citing works
Protracted Withdrawal From Benzodiazepines: The Post-Withdrawal Syndrome
Ashton, H. (1995) · Psychiatric Annals · doi:10.3928/0048-5713-19950301-11 · Cited by 32 · see citing works
- Authors
- Petursson, H., & Lader, M. H.
- Venue
- British Journal of Addiction
- Publisher
- Wiley
- Published
- 1981-06
- Volume
- 76
- Issue
- 2
- Pages
- 133-145
- ISSN
- 0952-0481 (ISSN-L)
- 2056-5178
- OpenAlex
- W4237016855
- Cited by
- 163
- References
- 86
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 2 · 2022: 1 · 2020: 4 · 2019: 2 · 2018: 1 · 2016: 1 · 2015: 1 · 2012: 1
- FWCI
- 3.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- British Journal of Addiction (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
- Health Sciences › Medicine › Geriatrics and Gerontology › Pharmaceutical Practices and Patient Outcomes
- Keywords
- benzodiazepine dependence, benzodiazepine withdrawal syndrome, anxiolytics, antiepileptic drugs, muscle relaxants, long-term benzodiazepine use
- MeSH terms
- Animals, Benzodiazepines, Chlordiazepoxide, Diazepam, Disease Models, Animal, Dose-Response Relationship, Drug, Drug Tolerance, Humans, Substance Withdrawal Syndrome, Substance-Related Disorders, Rats
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