title: Seizures with clonazepam: discontinuation and suggestions for safe discontinuation rates in children.
abstract: Clinical characteristics of clonazepam (CZP) discontinuation seizures were clarified from 17 patients who developed seizure exacerbation after rapid discontinuation, including abrupt discontinuation, reduction, or replacement with nitrazepam (NZP). Safe discontinuation rates of CZP were estimated by comparing these patients with 23 patients without CZP discontinuation seizures. The seizures consisted of status epilepticus or frequent attacks of generalized tonic-clonic seizures (GTC) or non-GTC, and the first attack of GTC. Incidence did not differ significantly between CZP-effective cases and CZP-ineffective cases at discontinuation. The reasons for abrupt discontinuation included adverse effects, insufficient efficacy, difficulty in taking CZP owing to pneumonia, or carelessness of the doctors or the families. Seizure exacerbation occurred 1-6 days after CZP discontinuation. Most of the problems improved with readministration of the original or smaller dosages of CZP or of NZP in an amount threefold or more greater than the original CZP dose. Safe discontinuation rates were estimated to be < or = 0.04 mg/kg for abrupt discontinuation, < or = 0.04 mg/kg/week for reduction, and replacement with NZP of 2.5 or more times the original amount of CZP. These safe discontinuation rates were prospectively confirmed by 84 cases of CZP discontinuation in 54 other patients, and no seizure exacerbation occurred with these discontinuation rates.
authors.affiliation: Division of Child Neurology, National Center Hospital for Mental, Nervous and Muscular Disorders, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Sugai
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D002998:Clonazepam / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004827:Epilepsy / Q000139:chemically induced* / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D009567:Nitrazepam / Q000008:administration & dosage / Q000627:therapeutic use; D011446:Prospective Studies; D013226:Status Epilepticus / Q000139:chemically induced; D013375:Substance Withdrawal Syndrome / Q000209:etiology / Q000517:prevention & control*
chemical_list: D002998:Clonazepam; D009567:Nitrazepam