An integrated analysis of acute treatment-emergent extrapyramidal syndrome in patients with schizophrenia during olanzapine clinical trials: comparisons with placebo, haloperidol, risperidone, or clozapine

J Clin Psychiatry. 2003 Aug;64(8):898-906. doi: 10.4088/jcp.v64n0807.


Background: The frequency and severity of extrapyramidal syndrome (EPS) were evaluated in patients with DSM-III or DSM-IV schizophrenia in the acute phase (- 8 weeks) of randomized, double-blind, controlled trials from the integrated olanzapine clinical trial database.

Method: This retrospective analysis included 23 clinical trials and 4611 patients from November 11, 1991, through July 31, 2001. Incidences of dystonic, parkinsonian, and akathisia events were compared using treatment-emergent adverse-event data. Categorical analyses of Simpson-Angus Scale and Barnes Akathisia Scale (BAS) scores, use of anticholinergic medications, and baseline-to-endpoint changes in Simpson-Angus Scale and BAS scores were compared.

Results: A significantly smaller percentage of olanzapine-treated patients experienced dystonic events than did haloperidol- (p <.001) or risperidone-treated patients (p =.047). A significantly greater percentage of haloperidol-treated patients experienced parkinsonian (p <.001) and akathisia (p <.001) events than did olanzapine-treated patients. Categorical analysis of Simpson-Angus Scale scores showed significantly more haloperidol- (p <.001) or risperidone-treated patients (p =.004) developed parkinsonism than did olanzapine-treated patients. Olanzapine-treated patients experienced significantly greater reductions in Simpson-Angus Scale scores than did haloperidol- (p <.001), risperidone- (p <.001), or clozapine-treated (p =.032) patients. Categorical analysis of BAS scores showed significantly more haloperidol-treated patients experienced treatment-emergent akathisia versus olanzapine-treated patients (p <.001). Significantly greater reductions in BAS scores were experienced during olanzapine treatment versus placebo (p =.007), haloperidol (p <.001), and risperidone (p =.004) treatments. A significantly smaller percentage of olanzapine-treated patients received anticholinergic medications compared with that of haloperidol- (p <.001) or risperidone-treated patients (p =.018). Compared with that in olanzapine-treated patients, the duration of anticholinergic cotreatment was significantly longer among haloperidol- (p <.001) or risperidone-treated patients (p =.040) and significantly shorter among clozapine-treated patients (p =.021).

Conclusion: This analysis of available data from olanzapine clinical trials lends additional support to olanzapine's favorable EPS profile.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Antipsychotic Agents / adverse effects*
  • Antipsychotic Agents / therapeutic use
  • Basal Ganglia Diseases / chemically induced*
  • Basal Ganglia Diseases / drug therapy
  • Benzodiazepines
  • Cholinergic Antagonists / therapeutic use
  • Clozapine / adverse effects
  • Clozapine / therapeutic use
  • Double-Blind Method
  • Female
  • Haloperidol / adverse effects
  • Haloperidol / therapeutic use
  • Humans
  • Male
  • Olanzapine
  • Pirenzepine / adverse effects*
  • Pirenzepine / analogs & derivatives*
  • Pirenzepine / therapeutic use
  • Placebos
  • Randomized Controlled Trials as Topic
  • Retrospective Studies
  • Risperidone / adverse effects
  • Risperidone / therapeutic use
  • Schizophrenia / drug therapy*


  • Antipsychotic Agents
  • Cholinergic Antagonists
  • Placebos
  • Benzodiazepines
  • Pirenzepine
  • Clozapine
  • Haloperidol
  • Risperidone
  • Olanzapine