title: Clinical outcome in a randomized 1-year trial of clozapine versus treatment as usual for patients with treatment-resistant illness and a history of mania.
abstract: OBJECTIVE
  Case series and follow-up studies suggest that clozapine may have mood-stabilizing properties in addition to antipsychotic action in patients with schizoaffective disorder, bipolar type, and bipolar I disorder, but the generalizability of these findings is limited. This article describes a randomized, open study of clozapine add-on therapy versus treatment as usual for patients with treatment-resistant illness and a history of mania.
  
  
  METHODS
  Thirty-eight patients meeting the DSM-IV criteria for schizoaffective or bipolar disorder that was deemed treatment-resistant were randomly assigned to clozapine add-on treatment (N = 19) or treatment as usual (no clozapine) (N = 19) and followed up for 1 year. Patients received monthly ratings on the Brief Psychiatric Rating Scale, Clinical Global Impression scale, Bech-Rafaelsen Mania Scale, Hamilton Depression Rating Scale, Scale for the Assessment of Positive Symptoms, Scale for the Assessment of Negative Symptoms, Abnormal Involuntary Movement Scale, and a 40-item side effect checklist. Differences between treatment groups were assessed according to a pattern-mix random-regression model. An additional analysis compared group differences in rating scale scores against relative time in the study.
  
  
  RESULTS
  Significant between-group differences were found in scores on all rating scales except the Hamilton depression scale. Total medication use over 1 year significantly decreased in the clozapine group. No significant differences between groups in somatic complaints were noted. The subjects with nonpsychotic bipolar I disorder who received clozapine showed a degree of improvement similar to that of the entire clozapine-treated group. Clozapine dose was significantly higher for the patients with schizoaffective illness than for those with bipolar disorder.
  
  
  CONCLUSIONS
  The results of this study support clozapine's independent mood-stabilizing property. They demonstrate that clozapine use was associated with significant clinical improvement relative to treatment as usual.
authors.affiliation: Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas 75235-9070, USA.
authors.forename: T
authors.initials: T
authors.lastname: Suppes
authors.forename: A
authors.initials: A
authors.lastname: Webb
authors.forename: B
authors.initials: B
authors.lastname: Paul
authors.forename: T
authors.initials: T
authors.lastname: Carmody
authors.forename: H
authors.initials: H
authors.lastname: Kraemer
authors.forename: A J
authors.initials: AJ
authors.lastname: Rush
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000517:prevention & control / Q000523:psychology; D003024:Clozapine / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D011618:Psychotic Disorders / Q000188:drug therapy* / Q000517:prevention & control / Q000523:psychology; D012044:Regression Analysis; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D001569:Benzodiazepines; D003024:Clozapine