{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T12:47:01Z","timestamp":1793191621353,"version":"4.5.0"},"reference-count":39,"publisher":"Georg Thieme Verlag KG","issue":"08","license":[{"start":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T00:00:00Z","timestamp":1757289600000},"content-version":"vor","delay-in-days":38,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arq Neuropsiquiatr"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Clobazam (CLB) has been an established treatment for epilepsy since the 1970s, with a broad spectrum. It is frequently used as add on therapy for refractory patients. Furthermore, it is different from classic benzodiazepines (BZD) for containing nitrogen atoms in 1 and 5 positions of B ring (other are 1.4-BZD). This explains why CLB has a better tolerability and a lower chance of causing sedation, being an excellent option for epilepsy treatment compared with other BZDs. Evidence argues against the development of CLB tolerance in most patients. Antiseizure medication shortages have been reported by many countries, including the one studied here. Shortages make treatment harder, increase the need for extra clinical appointments, for orientation and medication changes, increase medication errors, decrease adherence, and cause insecurity. A literature review showed scarce evidence of alternatives, with a wide variation in dosage equivalence. A survey of specialists revealed that switch appropriateness was deemed inadequate by the majority, due to risk of seizure worsening and side effects. Clonazepam and nitrazepam were the most used BZDs, but there was great variation for clonazepam dosages (0.25\u20132\u2009mg, commonly 1 per 10\u2009mg of CLB). Better consensus was obtained for nitrazepam (5 per 10\u2009mg of CLB). Gradual tapering of CLB, with concomitant increase of clonazepam or nitrazepam under close supervision, is advised. It is important to assess tolerability and the need for increased dosage. As CLB is an essential tool in the epilepsy armamentarium, shortages pose great risk to the patients. Governments and society must create mechanisms to prevent shortages of critical and unique medications.<\/jats:p>","DOI":"10.1055\/s-0045-1811235","type":"journal-article","created":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T23:05:27Z","timestamp":1757372727000},"page":"001-006","source":"Crossref","is-referenced-by-count":2,"title":["Which are the options and dosages for clobazam shortages on epilepsy treatment? Review of literature and survey of specialists"],"prefix":"10.1055","volume":"83","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2694-5120","authenticated-orcid":false,"given":"L\u00e9cio Figueira","family":"Pinto","sequence":"additional","affiliation":[{"name":"Universidade de S\u00e3o Paulo, Faculdade de Medicina, S\u00e3o Paulo SP, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5599-9120","authenticated-orcid":false,"given":"Guilherme Simone","family":"Mendon\u00e7a","sequence":"additional","affiliation":[{"name":"Hospital Santa Isabel, Blumenau SC, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9381-8674","authenticated-orcid":false,"given":"Carlos Alberto Mantovani","family":"Guerreiro","sequence":"additional","affiliation":[{"name":"Universidade Estadual de Campinas, Faculdade de Ci\u00eancias M\u00e9dicas, Campinas SP, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2025,9,8]]},"reference":[{"issue":"04","key":"ref1","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1007\/s11940-016-0401-x","article-title":"The Role of Benzodiazepines in the Treatment of Epilepsy","volume":"18","author":"J G Ochoa","year":"2016","journal-title":"Curr Treat Options Neurol"},{"issue":"07","key":"ref2","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1111\/cns.12399","article-title":"Clobazam: A Safe, Efficacious, and Newly Rediscovered Therapeutic for Epilepsy","volume":"21","author":"A C Gauthier","year":"2015","journal-title":"CNS Neurosci Ther"},{"issue":"02","key":"ref3","first-page":"209","article-title":"Effect of clobazam as add-on antiepileptic drug in patients with epilepsy","volume":"140","author":"R Joshi","year":"2014","journal-title":"Indian J Med Res"},{"issue":"04","key":"ref4","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1111\/j.1528-1157.1979.tb04825.x","article-title":"Antiepileptic properties of clobazam, a 1-5 benzodiazepine, in man","volume":"20","author":"H Gastaut","year":"1979","journal-title":"Epilepsia"},{"issue":"02","key":"ref5","first-page":"163","article-title":"Clobazam: The phoenix drug (from the very old to the brand new)","volume":"140","author":"C AM Guerreiro","year":"2014","journal-title":"Indian J Med Res"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.eplepsyres.2016.04.003","article-title":"Clobazam and clonazepam use in epilepsy: Results from a UK database incident user cohort study","volume":"123","author":"M J Brodie","year":"2016","journal-title":"Epilepsy Res"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1186\/1752-1947-8-429","article-title":"Clinical considerations in transitioning patients with epilepsy from clonazepam to clobazam: a case series","volume":"8","author":"R Sankar","year":"2014","journal-title":"J Med Case Rep"},{"issue":"09","key":"ref8","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1007\/s40263-023-01027-2","article-title":"New GABA-Targeting Therapies for the Treatment of Seizures and Epilepsy: I. Role of GABA as a Modulator of Seizure Activity and Recently Approved Medications Acting on the GABA System","volume":"37","author":"E Perucca","year":"2023","journal-title":"CNS Drugs"},{"issue":"02","key":"ref9","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1111\/j.1365-2125.1990.tb03616.x","article-title":"Respiratory and sedative effects of clobazam and clonazepam in volunteers","volume":"29","author":"J D Wildin","year":"1990","journal-title":"Br J Clin Pharmacol"},{"issue":"02","key":"ref10","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1111\/j.1600-0404.2008.01004.x","article-title":"Benzodiazepines in epilepsy: pharmacology and pharmacokinetics","volume":"118","author":"J Riss","year":"2008","journal-title":"Acta Neurol Scand"},{"issue":"02","key":"ref11","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1177\/0883073812463609","article-title":"Clobazam: a newly approved but well-established drug for the treatment of intractable epilepsy syndromes","volume":"28","author":"J W Wheless","year":"2013","journal-title":"J Child Neurol"},{"issue":"02","key":"ref12","doi-asserted-by":"publisher","first-page":"e88456","DOI":"10.1371\/journal.pone.0088456","article-title":"Clobazam and its active metabolite N-desmethylclobazam display significantly greater affinities for \u03b12- versus \u03b11-GABA(A)-receptor complexes","volume":"9","author":"H S Jensen","year":"2014","journal-title":"PLoS One"},{"issue":"03","key":"ref13","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1097\/FTD.0000000000000272","article-title":"Therapeutic Drug Monitoring of Clobazam and Its Metabolite-Impact of Age and Comedication on Pharmacokinetic Variability","volume":"38","author":"M L Burns","year":"2016","journal-title":"Ther Drug Monit"},{"issue":"S 01","key":"ref14","doi-asserted-by":"publisher","first-page":"139S","DOI":"10.1111\/j.1365-2125.1979.tb04684.x","article-title":"Review of clinical studies on clobazam","volume":"7","author":"D Koeppen","year":"1979","journal-title":"Br J Clin Pharmacol"},{"issue":"04","key":"ref15","doi-asserted-by":"publisher","first-page":"e36","DOI":"10.1111\/epi.17515","article-title":"A retrospective non-interventional study evaluating the pharmacokinetic interactions between cenobamate and clobazam","volume":"64","author":"S Elakkary","year":"2023","journal-title":"Epilepsia"},{"issue":"01","key":"ref16","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1017\/s0317167100016942","article-title":"Clobazam as add-on therapy for temporal lobe epilepsy and hippocampal sclerosis","volume":"32","author":"M A Montenegro","year":"2005","journal-title":"Can J Neurol Sci"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1590\/s0004-282x2006000500001","article-title":"Effectiveness of clobazam as add-on therapy in children with refractory focal epilepsy","volume":"64","author":"M RM da Silveira","year":"2006","journal-title":"Arq Neuropsiquiatr"},{"issue":"05","key":"ref18","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1111\/j.1528-1157.1987.tb03678.x","article-title":"Clobazam in therapy-resistant patients with partial epilepsy: a double-blind placebo-controlled crossover study","volume":"28","author":"D Koeppen","year":"1987","journal-title":"Epilepsia"},{"issue":"04","key":"ref19","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1046\/j.1528-1157.2001.31600.x","article-title":"Efficacy of clobazam as add-on therapy in patients with refractory partial epilepsy","volume":"42","author":"M A Montenegro","year":"2001","journal-title":"Epilepsia"},{"issue":"06","key":"ref20","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1097\/WNF.0b013e31815cd960","article-title":"Efficacy of clobazam as add-on therapy for refractory epilepsy: experience at a US epilepsy center","volume":"31","author":"M A Montenegro","year":"2008","journal-title":"Clin Neuropharmacol"},{"issue":"08","key":"ref21","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1001\/archneur.1986.00520080064023","article-title":"Clobazam for refractory focal epilepsy. A controlled trial","volume":"43","author":"D Schmidt","year":"1986","journal-title":"Arch Neurol"},{"issue":"06","key":"ref22","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1111\/j.1600-0404.1988.tb05947.x","article-title":"The long-term effect of clobazam as adjunctive therapy in epilepsy","volume":"77","author":"D F Scott","year":"1988","journal-title":"Acta Neurol Scand"},{"issue":"8289","key":"ref23","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/s0140-6736(82)91691-9","article-title":"Clobazam in catamenial epilepsy. A model for evaluating anticonvulsants","volume":"2","author":"M Feely","year":"1982","journal-title":"Lancet"},{"issue":"05","key":"ref24","doi-asserted-by":"publisher","first-page":"1158","DOI":"10.1111\/j.1528-1167.2008.01935.x","article-title":"Clobazam in the treatment of Lennox-Gastaut syndrome","volume":"50","author":"J A Conry","year":"2009","journal-title":"Epilepsia"},{"issue":"15","key":"ref25","doi-asserted-by":"publisher","first-page":"1473","DOI":"10.1212\/WNL.0b013e318232de76","article-title":"Randomized, phase III study results of clobazam in Lennox-Gastaut syndrome","volume":"77","author":"Y T Ng","year":"2011","journal-title":"Neurology"},{"issue":"10","key":"ref26","doi-asserted-by":"publisher","first-page":"CD009258","DOI":"10.1002\/14651858.CD009258.pub2","article-title":"Clobazam monotherapy for partial-onset or generalized-onset seizures","volume":"4","author":"R Arya","year":"2014","journal-title":"Cochrane Database Syst Rev"},{"issue":"09","key":"ref27","doi-asserted-by":"publisher","first-page":"952","DOI":"10.1111\/j.1528-1157.1998.tb01444.x","article-title":"Clobazam has equivalent efficacy to carbamazepine and phenytoin as monotherapy for childhood epilepsy","volume":"39","author":"F Booth","year":"1998","journal-title":"Epilepsia"},{"issue":"04","key":"ref28","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1016\/s1059-1311(02)00263-7","article-title":"Clobazam monotherapy in drug na\u00efve adult patients with epilepsy","volume":"12","author":"M M Mehndiratta","year":"2003","journal-title":"Seizure"},{"issue":"01","key":"ref29","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1212\/WNL.0000000000003253","article-title":"Clobazam and diazepam in anxiety","volume":"30","author":"K Rickels","year":"1981","journal-title":"Clin Pharmacol Ther"},{"issue":"08","key":"ref30","first-page":"296","article-title":"A placebo-controlled, double-blind comparison of clobazam and diazepam in the treatment of anxiety","volume":"44","author":"A F Jacobson","year":"1983","journal-title":"J Clin Psychiatry"},{"issue":"17","key":"ref31","doi-asserted-by":"publisher","first-page":"1806","DOI":"10.1212\/WNL.0000000000003253","article-title":"Deconstructing tolerance with clobazam: Post hoc analyses from an open-label extension study","volume":"87","author":"B E Gidal","year":"2016","journal-title":"Neurology"},{"issue":"02","key":"ref32","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1590\/s0004-282x2010000200024","article-title":"Modification in body weight associated with antiepileptic drugs","volume":"68","author":"C ND Gaspari","year":"2010","journal-title":"Arq Neuropsiquiatr"},{"issue":"06","key":"ref33","doi-asserted-by":"publisher","first-page":"19f13151","DOI":"10.4088\/JCP.19f13151","article-title":"Gestational Exposure to Benzodiazepines, 3: Clobazam and Major Congenital Malformations","volume":"80","author":"C Andrade","year":"2019","journal-title":"J Clin Psychiatry"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.seizure.2016.05.014","article-title":"Clobazam higher-evening differential dosing as an add-on therapy in refractory epilepsy","volume":"40","author":"S Thome-Souza","year":"2016","journal-title":"Seizure"},{"issue":"03","key":"ref35","doi-asserted-by":"publisher","first-page":"e227","DOI":"10.1212\/WNL.0000000000007778","article-title":"SUDEP in the North American SUDEP Registry: The full spectrum of epilepsies","volume":"93","author":"C Verducci","year":"2019","journal-title":"Neurology"},{"issue":"01","key":"ref36","doi-asserted-by":"publisher","first-page":"940","DOI":"10.1186\/s12913-022-08309-3","article-title":"National and transnational drug shortages: a quantitative descriptive study of public registers in Europe and the USA","volume":"22","author":"R Ravela","year":"2022","journal-title":"BMC Health Serv Res"},{"issue":"02","key":"ref37","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1111\/epi.13974","article-title":"A longitudinal cohort study on the impact of the clobazam shortage on patients with epilepsy","volume":"59","author":"S Lukmanji","year":"2018","journal-title":"Epilepsia"},{"issue":"05","key":"ref38","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1684\/epd.2022.1468","article-title":"Recommendations for treatment strategies in people with epilepsy during times of shortage of antiseizure medications","volume":"24","author":"A A Asadi-Pooya","year":"2022","journal-title":"Epileptic Disord"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"109690","DOI":"10.1016\/j.yebeh.2024.109690","article-title":"Seizure control and complications in patients switching from clobazam to clonazepam due to drug shortage","volume":"153","author":"O F\u0131rat","year":"2024","journal-title":"Epilepsy Behav"}],"container-title":["Arquivos de Neuro-Psiquiatria"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0045-1811235.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T23:05:31Z","timestamp":1757372731000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0045-1811235"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8]]},"references-count":39,"journal-issue":{"issue":"08","published-online":{"date-parts":[[2025,6,20]]},"published-print":{"date-parts":[[2025,8]]}},"alternative-id":["s00451811235"],"URL":"https:\/\/doi.org\/10.1055\/s-0045-1811235","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0004-282X","1678-4227"],"issn-type":[{"value":"0004-282X","type":"print"},{"value":"1678-4227","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8]]}}}