Evidence-Based Reviews

How to prevent hyperprolactinemia in patients taking antipsychotics

Current Psychiatry. 2003 February;2(2):57-64

References

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13. Turrone P, Kapur S, Seeman MV, Flint AJ. Elevation of prolactin levels by atypical antipsychotics. Am J Psychiatry 2002;159:133-5.

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15. Kleinberg DL, Davis JM, De Coster R, Van Baelen B, Brecher M. Prolactin levels and adverse events in patients treated with risperidone. J Clin Psychopharmacol 1999;19:57-61.

16. Conley RR, Mahmoud R. A randomized double-blind study of risperidone and olanzapine in the treatment of schizophrenia or schizoaffective disorder. Am J Psychiatry 2001;158:765-74.

17. Kim K, Pae C, Chae J, et al. Effects of olanzapine on prolactin levels of female patients with schizophrenia treated with risperidone. J Clin Psychiatry 2002;63:408-13.

Risperidone. A study sponsored by Janssen Pharmaceutica¹⁵ reviewed the manufacturer’s experience with prolactin and its potential to induce side effects, using data from premarketing studies comparing risperidone with haloperidol. Amenorrhea and galactorrhea were assessed in women; ejaculatory dysfunction, erectile dysfunction, and gynecomastia were assessed in men.

Table 3

HYPERPROLACTINEMIA-RELATED SIDE EFFECTS REPORTED BY PATIENTS TAKING RISPERIDONE AND OLANZAPINE

Gender and complaint	Taking risperidone (%)	Taking olanzapine (%)	Difference (P-value)
Women
Galactorrhea	11 of 47 (23.4%)	11 of 49 (22.4%)	1.00
Amenorrhea	11 of 46 (23.9%)	9 of 45 (20.0%)	0.80
Men
Gynecomastia	9 of 115 (7.8%)	4 of 115 (3.5%)	0.25
Sexual dysfunction	36 of 115 (31.3%)	34 of 114 (29.8%)	0.89
Source: Adapted and reprinted with permission from Conley RR, Mahmoud R. A randomized double-blind study of risperidone and olanzapine in the treatment of schizophrenia or schizoaffective disorder. Am J Psychiatry2001;158:765-74.

Both risperidone and haloperidol were associated with dose-related increases in plasma prolactin concentration in men and women. In women, neither risperidone dosage nor end-point prolactin concentrations were correlated with adverse events. In men:

adverse events did not correlate with plasma prolactin concentrations
the incidence of adverse events was dose-related
the incidence of adverse events associated with risperidone, 4 to 10 mg/d, was not significantly greater than in patients taking placebo.

Another Janssen-sponsored study compared potential hyperprolactinemia-related side effects of risperidone and olanzapine but did not report prolactin concentrations. The authors found no significant differences between the drugs, based on breast features/menstrual changes in women and chest features/sexual dysfunction in men (Table 3).¹⁶

Olanzapine. A study sponsored by Eli Lilly and Co.¹⁷ assessed the effects of olanzapine on prolactin concentration in women previously treated with risperidone. The authors enrolled 20 Korean women with schizophrenia treated with risperidone (mean dosage 3.5 mg/d) and complaining of menstrual disturbances, galactorrhea, and/or sexual dysfunction. The mean serum prolactin concentration with risperidone was 132.2 ng/ml.

Over 2 weeks, patients were switched from risperidone to olanzapine (mean dosage 9.1 mg/d). After 8 weeks, the mean serum prolactin concentration was measured at 23.4 ng/ml. The authors noted improved menstrual function and reduced sexual side effects with olanzapine.

Conclusion

The package inserts of all atypical antipsychotics list hyperprolactinemia as a potential risk in patients taking these medications. The clinical significance of hyperprolactinemia associated with antipsychotic use is being explored but requires further elucidation.

Based on our understanding of the long-term course of untreated hyperprolactinemia—derived largely from patients not taking antipsychotics—it seems reasonable to ask patients taking atypical antipsychotics at least once a year about chest/breast complaints and sexual dysfunction. This recommendation would seem particularly relevant in patients taking risperidone at dosages >6 mg/d for sustained periods. In the absence of specific complaints, hyperprolactinemia associated with risperidone should be evaluated case by case, including perhaps endocrinology consultation.

Related resources

Maguire GA. Prolactin elevation with antipsychotic medications: mechanisms of action and clinical consequences. J Clin Psychiatry 2002;63(suppl 4):56-62.
Smith S, Wheeler MJ, Murray R, O’Keane V. The effects of antipsychotic-induced hyperprolactinemia on the hypothalamic-pituitary-gonadal axis. J Clin Psychopharmacol 2002;22(2):109-14. Available at: http://www.psychiatry.wustl.edu/Resources/LiteratureList/2002/May/Smith.PDF.

Drug brand names

Clozapine • Clozaril
Haloperidol • Haldol
Olanzapine • Zyprexa
Quetiapine • Seroquel
Risperidone • Risperdal
Ziprasidone • Geodon

Disclosure

Dr. Vieweg reports that he is on the speakers bureau of Janssen Pharmaceutica, Eli Lilly and Co., Pfizer Inc., Wyeth Pharmaceuticals, Forest Pharmaceuticals, and GlaxoSmithKline.

Dr. Fernandez reports no financial relationship with any company whose products are mentioned in this article, or with manufacturers of competing products.