Prolactin levels in schizophrenia and schizoaffective disorder patients treated with clozapine, olanzapine, risperidone, or haloperidol

Background: Prolactin levels are elevated to varying degrees by antipsychotics. Prolactin elevations may result in sexual and other adverse effects, and they may be related to antipsychotic effects. We used the data collected in a trial of antipsychotics to study the differential effect of these drugs on prolactin level, to explore the relation between clinical effects and prolactin level, and to determine the relationship between plasma levels of antipsychotics and prolactin level. Method: Treatment-resistant patients (133 men, 24 women) diagnosed with DSM-IV schizophrenia or schizoaffective disorder participated in a double-blind, randomized, 14-week trial comparing clozapine (N = 40), olanzapine (N 39), risperidone (N = 41), and haloperidol (N 37). Plasma levels of prolactin and antipsychotics were determined at baseline and at weeks 5, 8, 10, 12, and 14 during the trial. Clinical effects were measured with the Positive and Negative Syndrome Scale and the Extrapyramidal Symptom Rating Scale. Statistical analyses were limited to the 75 men for whom repeated prolactin levels were available. Data were gathered from June 1996 to December 1999. Results: Risperidone caused significant elevation of prolactin levels (p < .05) that appeared to be dose-dependent. Clozapine and olanzapine were associated with decreases of prolactin, whereas haloperidol led to a minor, nonsignificant increase. Plasma olanzapine and prolactin levels were correlated. Prolactin levels were not related to clinical improvement or extrapyramidal side effects. Conclusion: Antipsychotics show major differences in their effects on prolactin, and risperidone has clearly the most robust effect.