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Title: Antipsychotic Medications Vary In Effect On Plasma Prolactin Levels

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J Clin Psychiatry 2004 Jan;65:1:57-61.
02/10/2004 10:25:00 AM
By Jill Taylor

Major differences in effect on plasma prolactin levels exist between antipsychotics, with risperidone showing the most robust effect, according to a new study. Although the pituitary secretion of prolactin is inhibited by dopamine, plasma prolactin is elevated by therapeutic doses of conventional antipsychotics. Because the therapeutic effect of antipsychotics is believed to depend on dopamine-blocking activity, prolactin levels may be indicative of antipsychotic efficacy. Exploring the relationship between clinical effects and prolactin level, Jan Volavka, MD, PhD, of the Nathan Kline Institute in Orangeburg, New York, United States, and colleagues performed a double-blind, randomised, 14-week study of 157 treatment-resistant patients with schizophrenia or schizoaffective disorder. Forty patients were assigned to treatment with clozapine, 39 to olanzapine, 41 to risperidone and 37 to haloperidol. Prolactin and drug blood levels were determined at baseline and weeks 5, 8, 10, 12, and 14. Prolactin levels at baseline and 1 or more timepoints during the treatment period were available in 75 male subjects. Analysis showed that risperidone caused significant elevation of prolactin levels. However, despite an observed dose-response relationship, there was no significant correlation between plasma levels of risperidone and prolactin. Alternatively, clozapine and olanzapine were associated with decreases of plasma prolactin. Olanzapine and prolactin plasma levels were significantly related when the olanzapine dose was 20 mg/day, a relationship that strengthened when dosage increased to a mean of 30.4 mg/day. Haloperidol led to minor increases in prolactin plasma levels that failed to reach significance. Prolactin levels were not associated with clinical improvement or extrapyramidal side effects. Possible explanations presented for this finding included modest clinical improvement and effective treatment of extrapyramidal side effects with benztropine. The study was supported in part by Janssen Pharmaceutica Research Foundation, Eli Lilly and Company, and Novartis Pharmaceuticals Corporation.

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