title: Cholinergic rebound and rapid onset psychosis following abrupt clozapine withdrawal.
abstract: Following the conduct of a 28-day inpatient bioequivalence study of clozapine in schizophrenia patients, withdrawal effects after abrupt discontinuation from clozapine were assessed. Thirty patients who met DSM-III-R criteria for schizophrenia, residual type, or schizophrenia in remission were enrolled in the study. Patients were evaluated for symptoms of withdrawal effects for 7 days after clozapine 200 mg/day was abruptly withdrawn. Of 28 patients who completed the study, 11 had no withdrawal symptoms; 12 had mild withdrawal adverse events of agitation, headache, or nausea; four patients experienced moderate withdrawal adverse events of nausea, vomiting, or diarrhea; and one patient experienced a rapid-onset psychotic episode requiring hospitalization. Cholinergic rebound is a likely explanation for the mild to moderate withdrawal symptoms and is easily treated with an anticholinergic agent. Mesolimbic supersensitivity, as well as specific properties of clozapine, are discussed as likely causes for rapidonset psychosis. Our findings are consistent with previous reports of withdrawal reactions associated with clozapine, further reminding clinicians to monitor patients closely following abrupt discontinuation of clozapine.
authors.affiliation: California Clinical Trials, Beverly Hills, USA.
authors.forename: T M
authors.initials: TM
authors.lastname: Shiovitz
authors.forename: T L
authors.initials: TL
authors.lastname: Welke
authors.forename: P D
authors.initials: PD
authors.lastname: Tigel
authors.forename: R
authors.initials: R
authors.lastname: Anand
authors.forename: R D
authors.initials: RD
authors.lastname: Hartman
authors.forename: J J
authors.initials: JJ
authors.lastname: Sramek
authors.forename: N M
authors.initials: NM
authors.lastname: Kurtz
authors.forename: N R
authors.initials: NR
authors.lastname: Cutler
mesh_terms: D000293:Adolescent; D000328:Adult; D017109:Akathisia, Drug-Induced / Q000209:etiology; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D003024:Clozapine / Q000008:administration & dosage / Q000009:adverse effects*; D003967:Diarrhea / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009460:Neurologic Examination / Q000187:drug effects; D011605:Psychoses, Substance-Induced / Q000209:etiology*; D011950:Receptors, Cholinergic / Q000187:drug effects*; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D013375:Substance Withdrawal Syndrome / Q000209:etiology*; D014839:Vomiting / Q000139:chemically induced
chemical_list: D014150:Antipsychotic Agents; D011950:Receptors, Cholinergic; D003024:Clozapine