Can olanzapine (Zyprexa) cause elevated levels of prolactin?/nA 29-year-old woman suffering from an

Fråga: Can olanzapine (Zyprexa) cause elevated levels of prolactin? A 29-year-old woman suffering from anxiety was treated earlier with risperidone (Risperdal). Because of elevated prolactin levels, 39 ug/l (normally <18 ug/l), and menstruation disturbances the treatment was stopped and olanzapine 10 mg daily was instituted in April 1999. The prolactin level was 7.1 ug/l at that time but has increased to 21 ug/l the 5:th of January 2000 and the patient developed menstruation disturbances again.

Sammanfattning: Olanzapine can cause transient elevations of prolactin levels both in men and women. Data suggest that women are more sensitive to dopamine blockade than men and thus are more prone to develop hyperprolactinemia. Dose reduction is a possible way to minimise the effect on prolactin levels. Determination of plasma levels of olanzapine can be of help.

Svar: It is well known that classical antipsychotics can cause elevated prolactin levels (1). The mechanism is mainly due to dopamine receptor antagonism in the hypothalamus and anterior pituitary. Risperidone acts as a potent 5-HT-2 and D2 antagonist with effects on the endocrine system such as increased prolactin levels (2). There are several case reports of increased prolactin levels and galactorrhea during risperidone treatment (3).

Olanzapine and clozapine are atypical antipsychotics and have a different adverse reaction profile compared with other antipsychotics. Since both have a low D2-receptor affinity they are not expected to increase prolactin levels to a significant degree.

In a study on 128 male subjects olanzapine produced a modest elevation of serum prolactin. The elevations were dose-dependent and decreased after six weeks of treatment (4). Another study on 166 men showed a transient dose-dependent increase in prolactin levels but within normal laboratory values for prolactin (5).

Olanzapine is used as an alternative in patients with hyperprolactinemia caused by other antipsychotics (6). In one report two women were instituted on perphenazine and risperidone respectively. Both experienced amenorrhea and galactorrhea and lab test revealed elevated serum prolactin levels (>200 ug/l and 127 ug/l respectively). Treatment with olanzapine was instituted with decreasing levels of prolactin. The patients symptoms declined slowly and after one month monthly menses resumed and galactorrhea resolved. The first patient continued to have moderate prolactin elevation after 6 months. It is assumed that women have greater sensitivity than men to dopamine blockade (6). In a study on 20 males and seven females treated with olanzapine, a significant difference between men and women was found. Eight weeks after olanzapine was instituted the difference in plasma concentrations of olanzapine was 85 per cent greater in women than in men (9).

A search in the WHO database of adverse reactions revealed 43 unvalidated cases of hyperprolactinemia or nonpuerperal lactation in connection to olanzapine treatment (7).

One case of hyperprolactinemia related to olanzapine has been located in SWEDIS. A 52-year-old woman with schizophrenia developed defluvium (hair loss) one month after change from thioridazin to olanzapine 5-10 mg daily. After six months of treatment her serum prolactin increased to 86.9 ug/l (8).