title: Switching to Clozapine Using Immediate Versus Gradual Antipsychotic Discontinuation: A Pilot, Double-Blind, Randomized Controlled Trial.
abstract: To examine effects of different antipsychotic discontinuation strategies on clinical outcomes in patients with schizophrenia undergoing a switch to clozapine.
  
  
  
  This pilot, 8-week, double-blind, randomized controlled trial was conducted from May 1999 to July 2004. Outpatients with a diagnosis of schizophrenia or schizoaffective disorder based on the Structured Clinical Interview for DSM-IV and eligible for a switch to clozapine were included. Participants were randomly assigned to the immediate discontinuation (prior antipsychotics were discontinued at baseline) or gradual discontinuation (prior antipsychotics were reduced by 25% each week) group. For each group, clozapine was gradually increased to 300 mg/d at day 12, with this dose maintained for 3 weeks and thereafter adjusted as needed. Clinical outcome measures included the Brief Psychiatric Rating Scale (BPRS), UKU Side Effect Rating Scale, and extrapyramidal symptoms scales.
  
  
  
  Thirty-three patients were enrolled; 15 and 18 patients were assigned to the immediate and gradual discontinuation groups, respectively. While significant improvements were observed in BPRS total scores after the switch to clozapine in both groups (P values < .001), no significant differences were found on any clinical outcome measures between the groups; however, additional analyses revealed a significant interaction between group and time for the UKU Psychic Side Effects subscale scores (P = .038).
  
  
  
  This preliminary study demonstrated no statistically significant differences in efficacy or tolerability between immediate and gradual antipsychotic discontinuation strategies when switching to clozapine in patients with schizophrenia; however, due to the small sample size, larger-scale trials are needed to confirm these results.
  
  
  
  ClinicalTrials.gov identifier: NCT02640300.
authors.affiliation: Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, Canada.|Department of Psychiatry, University of Toronto, Canada.|Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Takeuchi
authors.affiliation: Department of General Psychiatry 1, Institute of Mental Health, Singapore.|Office of Clinical Sciences, Duke-NUS Graduate Medical School, Singapore.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Lee
authors.affiliation: Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, Canada.|Institute of Medical Science, University of Toronto, Canada.
authors.forename: Gagan
authors.initials: G
authors.lastname: Fervaha
authors.affiliation: Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, Canada.|Department of Psychiatry, University of Toronto, Canada.|Institute of Medical Science, University of Toronto, Canada.
authors.forename: George
authors.initials: G
authors.lastname: Foussias
authors.affiliation: Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, Canada.|Department of Psychiatry, University of Toronto, Canada.|Institute of Medical Science, University of Toronto, Canada.
authors.forename: Ofer
authors.initials: O
authors.lastname: Agid
authors.affiliation: Schizophrenia Division, Centre for Addiction and Mental Health, 250 College St, Toronto, Ontario, M5T 1R8, Canada. gary.remington@camh.ca.|Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, Canada.|Department of Psychiatry, University of Toronto, Canada.|Institute of Medical Science, University of Toronto, Canada.
authors.forename: Gary
authors.initials: G
authors.lastname: Remington
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D003024:Clozapine / Q000009:adverse effects* / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D057915:Drug Substitution / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D003024:Clozapine