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NEW YORK — Antipsychotics can induce elevated levels of prolactin that may require dosage changes or medication switches, Dr. Harold E. Carlson said at a psychopharmacology update sponsored by the American Academy of Child and Adolescent Psychiatry.
Psychiatrists may refer patients who are taking antipsychotics because their patients are experiencing missed menses, nipple discharge, sexual dysfunction, or delays in pubertal development, all of which are signs and symptoms of hyper-prolactinemia, said Dr. Carlson, chief of the division of endocrinology at the State University of New York at Stony Brook.

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Prolactin suppresses the release of gonadotropin-releasing hormone from the hypothalamus, which leads to hypogonadism by lowering serum levels of luteinizing hormone and follicle-stimulating hormone. Prolactin also is known to stimulate lactation. Dopamine inhibits the release of prolactin by binding to D2 dopamine receptors in the pituitary gland. Most antipsychotics, especially atypical antipsychotics, have D2-dopamine antagonist activity. They raise serum prolactin levels by varying degrees because they vary in their antagonist activity on, and affinity for, the D2 dopamine receptors.
In general, serum prolactin levels are raised the most by risperidone (Risperdal), followed by haloperidol (Haldol), olanzapine (Zyprexa), ziprasidone (Geodon), quetiapine (Seroquel), clozapine (Clozaril), and aripiprazole (Abilify). Quetiapine and clozapine are “pretty neutral” in their effect on serum prolactin levels, while aripiprazole is actually a partial D2-receptor agonist and suppresses serum prolactin to below baseline levels, Dr. Carlson said.
Patients with elevated serum prolactin levels should receive a pregnancy test (when appropriate) and tests of serum levels of thyroid-stimulating hormone (in case of hypothyroidism) and creatinine (in case of renal insufficiency) to rule out these three “very common” causes of hyperprolactinemia, he said.
Once an antipsychotic is established as the cause of elevated prolactin, one could try reducing the dose of the drug or switching to a more prolactin-sparing antipsychotic–if medically feasible–when the level of serum prolactin is less than 200 ng/mL, Dr. Carlson advised. When the concentration of serum prolactin is greater than 200 ng/mL or does not change after a switch to a prolactin-sparing antipsychotic, he suggested performing an MRI scan of the sella turcica area of the brain to look for a prolactin-secreting tumor, such as a pituitary adenoma or a tumor that obstructs dopamine production, such as a parasellar tumor. Many years of observational data suggest that antipsychotic drugs probably do not induce prolactin-secreting pituitary tumors, he added.
Normal MRI results would indicate treatment of patients’ hypogonadal symptoms with birth-control pills for women and testosterone for men. Osteoporosis medications could be started if appropriate.
Some case reports have described a reduction in the symptoms of antipsychotic-induced hyperprolactinemia with the use of dopamine agonists such as caber-goline or amantadine, but in other cases the psychotic symptoms worsened.
Increased serum prolactin levels have been reported to decline over time in some cases, even when treatment with antipsychotics continued, Dr. Carlson noted.
Antipsychotics usually elevate prolactin levels more in women than in men because estrogen enhances responsiveness to prolactin. Several studies have found that the probability of abnormal menses rises linearly as the level of serum prolactin rises. The probability increases from nearly 40% at 50 ng/mL of prolactin to more than 60% at 150 ng/mL (Psychoneuroen-docrinology 2003;28[suppl. 2]:55-68).
In an as-yet unpublished 12-week study of 290 patients (97 women), some women missed one or more menstrual periods during treatment with olanzapine (13%, 3 of 23), risperidone (18%, 6 of 34), and ziprasidone (22%, 2 of 9), compared with none in 31 women who took clozapine, quetiapine, or aripiprazole, he said.
Decreased libido or erectile dysfunction occurred most often with risperidone (26%, 23 of 89), followed by olanzapine (19%, 13 of 68), ziprasidone (17%, 3 of 18), quetiapine (9%, 5 of 54), aripiprazole (9%, 5 of 56), and clozapine (0 of 5). Olanzapine was the only drug to cause galactorrhea in the patients (5%, 4 of 87).
BY JEFF EVANS
Senior Writer
COPYRIGHT 2006 International Medical News Group
COPYRIGHT 2008 Gale, Cengage Learning