Benzodiazepine Withdrawal Seizures: Analysis of 48 Case Reports
Abstract
Summary Various reactions to benzodiazepine withdrawal have been widely described. Among these, seizures have occasionally occurred on abrupt withdrawal. Our own experience of 48 cases of seizures suspected to have been caused by benzodiazepine withdrawal and reported to the Adverse Drug Reaction (ADR) Monitoring Center (1979–1985) showed that a great variety of ben-zodiazepines with different half-lives were involved, those most frequently implicated being the most widely prescribed. The occurrence of seizures was not always related to the interruption of long-term treatment (from a few days to >7 years) nor to high-dose treatment, the range of dosages being usually close to that recommended. However, in some cases, several benzodiazepines had been taken simultaneously. The time between the last intake of the drug(s) and the occurrence of the seizures was shorter when a short-life benzodiazepine had been used. Additional factors were frequently involved; these factors were present in 29 cases and were multiple in nine of them. The incidence of withdrawal seizures was related more to the presence of these additional factors than to either the pharmacokinetics of the drugs or the pattern of treatment.
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Some studies have reported epileptic seizures following abrupt discontinuation of benzodiazepines and recommend a gradual reduction over at least 6 days to avoid convulsions.
“Some studies have reported epileptic seizures [57] following an abrupt discontinuation of BZDs, and hence recommend a gradual reduction over at least 6 days to avoid convulsions [58].”
From Cognitive behavioral therapy and acceptance and commitment therapy for the discontinuation of long-term benzodiazepine use in insomnia and anxiety disorders (2021) · cites this paper as [57]
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Jacobsen, E. J., Stelzer, L. S., Belonga, K. L., et al. (1996) · Journal of Medicinal Chemistry · doi:10.1021/jm960070+ · Cited by 91 · see citing works
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Beleza, P. (2012) · The Neurologist · doi:10.1097/nrl.0b013e318251e6c3 · Cited by 68 · see citing works
Chapoutot, M., Peter-Derex, L., Bastuji, H., Leslie, W., Schoendorff, B., Heinzer, R., Siclari, F., Nicolas, A., Lemoine, P., Higgins, S., et al. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph181910222 · Cited by 59 · see citing works
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BackgroundPoncer, J. C., Dürr, R., Gähwiler, B. H., & Thompson, S. M. (1996) · Neuropharmacology · doi:10.1016/s0028-3908(96)00055-x · Cited by 59 · see citing works
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(1994) · American Journal of Psychiatry · doi:10.1176/ajp.151.12.1760 · Cited by 44 · see citing works
Liebrenz, M., Gehring, M.-T., Buadze, A., & Caflisch, C. (2015) · BMC Psychiatry · doi:10.1186/s12888-015-0493-y · Cited by 40 · see citing works
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Landry, P., & Mainguy, N. (2004) · Santé mentale au Québec · doi:10.7202/008616ar · Cited by 4 · see citing works
“…observés durant les jours qui suivent une diminution importante de la dose ou la cessation de la médication, notamment l’anxiété rebond, l’insomnie rebond (Gillin et al., 1989) et les convulsions liées principalement à l’arrêt brusque de la médication (Fialip et al., 1987 ; Gatzonis et al., 2000).”
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Allergy to antibacterials: the problem with beta-lactams and sulfonamides
Cerny, A., & Pichler, W. J. (1998) · Pharmacoepidemiology and Drug Safety · doi:10.1002/(sici)1099-1557(199808)7:1+ · Cited by 6 · see citing works
Self-citationUrsachen und Diagnosekriterien von Gelegenheitsanfällen
Duarte, Y. M., & Bauer, J. M. (2005) · Clinical Epileptology · doi:10.1007/s10309-005-0125-5 · Cited by 2 · see citing works
“Epileptische Anfälle sind noch nach einem Zeitraum von zwei Wochen nach Absetzen der Benzodiazepine beobachtet worden [19].”
BackgroundChapoutot, M., Gustin, M., Anders, R., Peter‐Derex, L., Bastuji, H., Khazaal, Y., & Putois, B. (2025) · Sleep Medicine · doi:10.1016/j.sleep.2025.108744 · Cited by 1 · see citing works
Baron, D., Touzé, M. D., & Potel, G. (1992) · Réanimation Urgences · doi:10.1016/s1164-6756(05)80528-6 · Cited by 1 · see citing works
Illicit Drugs II: Opioids, Cocaine, and Others
Brust, J. C. M. (2009) · Elsevier eBooks · doi:10.1016/b978-032305260-3.50034-4 · Cited by 1 · see citing works
Seizures, Illicit Drugs, and Ethanol
Brust, J. C. M. (2012) · Springer eBooks · doi:10.1007/978-1-4614-3375-0_27 · Cited by 1 · see citing works
Schmalbach, B., & Lang, N. (2014) · NeuroTransmitter · doi:10.1007/s15016-014-0566-z · Cited by 1 · see citing works
“Durch Down-Regulation von GABA-Rezeptoren entstehen vermutlich Anfälle nach plötzlichem Absetzen von Barbituraten, Benzodiazepinen und anderen Seadativa wie Chloralhydrat, Meprobamat und Zolpidem [19, 20, 21].”
BackgroundPrincipales urgences iatrogènes médicamenteuses
Gautier, S., Bordet, R., & Caron, J. (2006) · EMC - Médecine d urgence · doi:10.1016/s1959-5182(06)73445-6
“La symptomatologie convulsivante survient habituellement dans les 24 ou 48 heures suivant l’arrêt du médicament, parfois plus tardivement si la demi-vie d’élimination du produit est longue [39].”
Drislane, F. W. (1997) · Elsevier eBooks · doi:10.1016/b978-012621355-3/50009-8
Anxiolytics: Misuse, Dependence, and Withdrawal Syndromes
Tang, V. M., & Davies, S. (2020) · Springer eBooks · doi:10.1007/978-3-319-56015-1_405-1
Jerram, T. C. (1989) · Side effects of drugs annual · doi:10.1016/s0378-6080(89)80010-8
(2000) · Time to knit · doi:10.1016/s0000-0000(07)43620-8
(2000) · Time to knit · doi:10.1016/s1241-8234(02)00038-x
(2000) · Time to knit · doi:10.1016/s1241-8234(96)24747-9
Slíva, J. (2025) · Medicína pro praxi · doi:10.36290/med.2025.023
Barbituriques et autres hypnotiques et sédatifs
Brust, J. C. M. (2007) · Elsevier eBooks · doi:10.1016/b978-2-84299-712-0.50006-1
Epilepsie und Substanzabusus im Visier
Höfler, J., & Trinka, E. (2015) · psychopraxis neuropraxis · doi:10.1007/s00739-015-0272-z
- Authors
- Fialip, J., Aumaitre, O., Eschalier, A., Maradeix, B., Dordain, G., & Lavarenne, J.
- ORCID
- Eschalier, A.
- Venue
- Clinical Neuropharmacology
- Published
- 1987-12
- Volume
- 10
- Issue
- 6
- Pages
- 538-544
- ISSN
- 0362-5664 (ISSN-L)
- OpenAlex
- W4323254080
- Cited by
- 53
- References
- 0
- Citations by year
- 2025: 2 · 2024: 1 · 2022: 2 · 2021: 3 · 2020: 2 · 2018: 1 · 2015: 2 · 2014: 1 · 2012: 2
- FWCI
- 2.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Neuropharmacology (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- benzodiazepine withdrawal, withdrawal seizures, adverse drug reactions, abrupt discontinuation, risk factors
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