title: Clozapine and risperidone in moderately refractory schizophrenia: a 6-month randomized double-blind comparison.
abstract: OBJECTIVE
  Clozapine remains the only medication indicated for refractory schizophrenia. As new antipsychotic drugs become available, their efficacy compared to clozapine, particularly in moderately ill patients, is of great clinical interest. We compared risperidone, the first of these, to clozapine in partially responsive patients. Further, since participation of patients usually excluded from clinical trials is increasingly important, we broadened inclusion to a wider patient population.
  
  
  METHODS
  We compared clozapine (n = 53) to risperidone (n = 54) in a randomized, double-blind, 29-week trial in schizophrenia patients (diagnosed using DSM-IV) at 3 research outpatient clinics. Randomization was stratified by "narrow" or "broad" inclusion criteria. The study was conducted between December 1995 and October 1999. Time to treatment discontinuation for lack of efficacy and time to 20% improvement in the Brief Psychiatric Rating Scale psychotic symptom cluster were the primary outcome measures.
  
  
  RESULTS
  There were no differences in all-cause discontinuation; clozapine-treated participants were significantly less likely to discontinue for lack of efficacy (15%) than risperidone-treated participants (38%) (Wilcoxon χ(2)1 = 6.10, P = .01). Clozapine resulted in significantly more global improvement (F2,839 = 6.07, P < .01) and asociality improvement (F2,315 = 6.64, P < .01) than risperidone. There was no difference in proportions meeting an a priori criterion of psychosis improvement (risperidone: 57%; clozapine: 71%). Significant adverse effect differences in salivation (F1 = 4.05, P < .05) (F1 = 12.13, P < .001), sweating (F1 = 5.07, P < .05), and tachycardia (F1 = 6.51, P < .05) favored risperidone.
  
  
  CONCLUSIONS
  Clozapine-treated partially responsive patients were less likely to discontinue treatment for lack of efficacy and improved more globally than those treated with risperidone, although psychotic symptoms did not differ. These findings suggest that clozapine should not be restricted to the most severely ill, treatment-refractory patients; it should be considered as an alternative for patients who have some response to other antipsychotics, but still experience troubling symptoms.
authors.affiliation: 75-59 263rd St, The Zucker Hillside Hospital, Glen Oaks, NY 11004 nina.schooler@gmail.com.
authors.forename: Nina R
authors.initials: NR
authors.lastname: Schooler
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Marder
authors.forename: K N R
authors.initials: KN
authors.lastname: Chengappa
authors.forename: Georgios
authors.initials: G
authors.lastname: Petrides
authors.forename: Donna
authors.initials: D
authors.lastname: Ames
authors.forename: William C
authors.initials: WC
authors.lastname: Wirshing
authors.forename: Marjorie
authors.initials: M
authors.lastname: McMeniman
authors.forename: Robert W
authors.initials: RW
authors.lastname: Baker
authors.forename: Haranath
authors.initials: H
authors.lastname: Parepally
authors.forename: Daniel
authors.initials: D
authors.lastname: Umbricht
authors.forename: John M
authors.initials: JM
authors.lastname: Kane
mesh_terms: D010054:Brief Psychiatric Rating Scale; D003024:Clozapine / Q000009:adverse effects* / Q000627:therapeutic use*; D015897:Comorbidity; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004351:Drug Resistance; D006801:Humans; D011618:Psychotic Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D018967:Risperidone / Q000009:adverse effects* / Q000627:therapeutic use*; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D016896:Treatment Outcome
chemical_list: D003024:Clozapine; D018967:Risperidone