Comparative efficacy of olanzapine and haloperidol for patients with treatment-resistant schizophrenia

Biol Psychiatry. 1999 Feb 15;45(4):403-11. doi: 10.1016/s0006-3223(98)00291-1.


Background: There is relatively little information regarding the efficacy of newer atypical antipsychotic drugs for patients with schizophrenia who are treatment-resistant to neuroleptic agents. Several lines of evidence suggest that a clinical trial of olanzapine in this population is warranted.

Methods: A subpopulation of patients (n = 526) meeting treatment-resistant criteria selected from a large, prospective, double-blind, 6-week study assessing the efficacy and safety of olanzapine and haloperidol were examined. Both last-observation-carried-forward (LOCF) and completers (observed cases) analyses were conducted.

Results: Olanzapine demonstrated significantly greater mean improvement from baseline in Positive and Negative Syndrome Scale (PANSS) negative symptoms, comorbid depressive symptoms assessed by the Montgomery-Asberg Depression Rating Scale, akathisia as measured by Barnes Akathisia Scale, and extrapyramidal symptoms as measured by Simpson-Angus Extrapyramidal Rating Scale with both LOCF and completers analyses. In addition, olanzapine was significantly superior to haloperidol for Brief Psychiatric Rating Scale total (p = .006), PANSS total (p = .005), and PANSS positive symptoms (p = .017) in completers of the 6-week study. Significantly greater response rates were observed in olanzapine-treated (47%) than haloperidol-treated (35%) patients in the LOCF analysis (p = .008), but significance was not reached in the completers analysis (p = .093). Mean doses (+/- SD) of olanzapine and haloperidol were 11.1 +/- 3.4 mg/day and 10.0 +/- 3.6 mg/day, respectively.

Conclusions: Olanzapine was superior to haloperidol for key symptom domains and parkinsonian side effects. Implications of these data for the therapeutics of this severely ill subgroup are discussed.

Publication types

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

MeSH terms

  • Adult
  • Akathisia, Drug-Induced
  • Analysis of Variance
  • Antipsychotic Agents / therapeutic use*
  • Behavioral Symptoms / chemically induced
  • Behavioral Symptoms / drug therapy
  • Benzodiazepines
  • Chi-Square Distribution
  • Double-Blind Method
  • Drug Resistance
  • Dyskinesia, Drug-Induced
  • Female
  • Haloperidol / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Olanzapine
  • Pirenzepine / analogs & derivatives*
  • Pirenzepine / therapeutic use
  • Prospective Studies
  • Schizophrenia / drug therapy*
  • Treatment Outcome


  • Antipsychotic Agents
  • Benzodiazepines
  • Pirenzepine
  • Haloperidol
  • Olanzapine