The effects of olanzapine, risperidone, and haloperidol on plasma prolactin levels in patients with schizophrenia

Clin Ther. 2000 Sep;22(9):1085-96. doi: 10.1016/S0149-2918(00)80086-7.


Background: There is relatively little comparative information on elevations in plasma prolactin level (PRL) with conventional versus novel antipsychotic agents.

Objective: This paper examines the comparative effects on PRL of olanzapine, risperidone, and haloperidol based on data from 3 multicenter, double-blind, randomized clinical trials. Magnitude of response, dose dependency, time course, effects of sex and age, and response to switching from haloperidol to olanzapine are assessed.

Methods: The effects of olanzapine, risperidone, and haloperidol on PRL were assessed in patients with schizophrenia or related psychoses participating in 3 double-blind clinical trials: (1) a 6-week acute trial comparing olanzapine 5 to 20 mg/d (n = 1,336) and haloperidol 5 to 20 mg/d (n = 660), with a 1-year, open-label olanzapine extension for responders; (2) a 54-week study comparing olanzapine 5 to 20 mg/d (n = 21), risperidone 4 to 10 mg/d (n = 21), and haloperidol 5 to 20 mg/d (n = 23) in early illness; and (3) a 28-week study comparing olanzapine 10 to 20 mg/d (n = 172) and risperidone 4 to 12 mg/d (n = 167).

Results: PRL elevations were significantly greater with risperidone than with either olanzapine or haloperidol in study 2. and significantly greater than with olanzapine in study 3 (all, P < 0.001). PRL elevations were significantly greater with haloperidol than with olanzapine in study 1 (P < 0.001 ). A dose-response relationship was not consistently confirmed with any of the drug treatments. Risperidone-associated PRL elevations peaked relatively early in treatment. In haloperidol- and risperidone-treated patients, the mean change in PRL was greater in women than in men. PRL decreased significantly when treatment was switched from haloperidol to olanzapine.

Conclusions: This side-by-side analysis of 3 independent studies suggests that with the 3 antipsychotic drugs studied, PRL is elevated moderately by olanzapine (mean change, 1-4 ng/mL), intermediately by haloperidol (mean change, approximately 17 ng/mL), and strongly by risperidone (mean change, 45-80 ng/mL). No consistent dose-response relationship was observed, and the time course and sex-dependency of the response differed between the 3 agents. Patients with haloperidol-induced hyperprolactinemia may benefit from a switch to olanzapine. Long-term studies examining the health consequences of chronic hyperprolactinemia during antipsychotic treatment are needed.

Publication types

  • Meta-Analysis

MeSH terms

  • Antipsychotic Agents / therapeutic use*
  • Benzodiazepines
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Haloperidol / therapeutic use*
  • Humans
  • Olanzapine
  • Pirenzepine / analogs & derivatives*
  • Pirenzepine / therapeutic use*
  • Prolactin / blood*
  • Risperidone / therapeutic use*
  • Schizophrenia / blood
  • Schizophrenia / drug therapy*


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