Clozapine, olanzapine, risperidone, and haloperidol in the treatment of patients with chronic schizophrenia and schizoaffective disorder

Am J Psychiatry. 2002 Feb;159(2):255-62. doi: 10.1176/appi.ajp.159.2.255.


Objective: The authors compared the efficacy and safety of three atypical antipsychotics (clozapine, olanzapine, and risperidone) with one another and with haloperidol in the treatment of patients with chronic schizophrenia or schizoaffective disorder.

Method: In a double-blind trial, 157 inpatients with a history of suboptimal treatment response were randomly assigned to treatment with clozapine, olanzapine, risperidone, or haloperidol for 14 weeks (an 8-week escalation and fixed-dose period followed by a 6-week variable-dose period).

Results: Clozapine, risperidone, and olanzapine (but not haloperidol) resulted in statistically significant improvements in total score on the Positive and Negative Syndrome Scale. Improvements seen in total and negative symptom scores with clozapine and olanzapine were superior to haloperidol. The atypical drugs, particularly olanzapine and clozapine, were associated with weight gain.

Conclusions: The effects of atypical antipsychotics in this population were statistically significant but clinically modest. The overall pattern of results suggests that clozapine and olanzapine have similar general antipsychotic efficacy and that risperidone may be somewhat less effective. Clozapine was the most effective treatment for negative symptoms. However, the differences among treatments were small.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / therapeutic use*
  • Benzodiazepines
  • Chronic Disease
  • Clozapine / adverse effects
  • Clozapine / therapeutic use
  • Double-Blind Method
  • Female
  • Haloperidol / adverse effects
  • Haloperidol / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Olanzapine
  • Patient Admission
  • Pirenzepine / adverse effects
  • Pirenzepine / analogs & derivatives*
  • Pirenzepine / therapeutic use
  • Psychiatric Status Rating Scales
  • Psychotic Disorders / diagnosis
  • Psychotic Disorders / drug therapy*
  • Psychotic Disorders / psychology
  • Risperidone / adverse effects
  • Risperidone / therapeutic use
  • Schizophrenia / diagnosis
  • Schizophrenia / drug therapy*
  • Schizophrenic Psychology*
  • Treatment Outcome


  • Antipsychotic Agents
  • Benzodiazepines
  • Pirenzepine
  • Clozapine
  • Haloperidol
  • Risperidone
  • Olanzapine