NEW YORK – A bit of aripiprazole could be just enough to bring down stubborn prolactin levels for a patient who is otherwise responding well to a specific antipsychotic, according to Dr. Harold E. Carlson.
Unlike most antipsychotics, which have antagonistic activity at the dopamine-2 receptors, aripiprazole is a dopamine receptor agonist. As such, it does not have the same dopamine-blocking effect – which allows dopamine to continue regulating prolactin production in the pituitary gland, Dr. Carlson said at a psychopharmacology update held by the American Academy of Child and Adolescent Psychiatry.
Dr. Harold Carlson
"This gives it the ability to actually lower prolactin, which is something we can use therapeutically," said Dr. Carlson, chief of the division of endocrinology at Stony Brook (N.Y.) University.
Hyperprolactinemia is a common side effect of many antipsychotic medications. Risperidone, paliperidone, and haloperidol are almost certain to cause it. The easiest way to address this hormonal imbalance is simply by switching to a different antipsychotic, he said. Ziprasidone is less likely to provoke a prolactin increase than the three older medications. Others – in order of decreasing probability – are lurasidone, iloperidone, quetiapine, asenapine, clozapine, and finally, aripiprazole.
But it’s not necessary to measure everyone’s prolactin, he cautioned. Many patients tolerate an increased level with no symptoms at all.
"If things are normal, don’t bother," he said. "It will lead you down the garden path. If you measure it and it’s mildly elevated, then you are committed to monitor it forever."
Having said that, he cautioned, it is important to ask patients about any issues – menses, for example. "If a young lady says she has missed her period, then I measure it." It also is important to perform a pregnancy test, he said.
Unpublished data collected by Dr. Christoph U. Correll show how effectively an antipsychotic switch can modulate prolactin, Dr. Carlson said. Dr. Correll of the Zucker Hillside Hospital, Glen Oaks, N.Y., found that patients who switched from aripiprazole to quetiapine had an increase in prolactin level. Prolactin decreased in those who switched to quetiapine from olanzapine, risperidone, or ziprasidone.
"You can often switch to a great benefit, assuming that the drug you switch to is as beneficial as the one you switched from," Dr. Carlson said. But if the most effective antipsychotic is also one of the big prolactin-increasers, "you’re better off to combine it with another drug like aripiprazole, which will minimize the degree of hyperprolactinemia."
The seminal study of this technique was published in 2007 (Am. J. Psychiatry 2007;164:1404-10).It comprised 56 adults who developed hyperprolactinemia while taking haloperidol. Patients were randomized to stay on haloperidol alone or to add aripiprazole (15 mg/day for 4 weeks followed by 30 mg/day for 8 weeks).
By week 8, 88% of those taking aripiprazole had normal prolactin levels, compared with about 4% of those in the placebo group. Seven of the 11 nonmenstruating women in the study resumed menses. There was no clinically significant interaction of the two medications, and haloperidol serum levels were stable.
Last year, a smaller study looked at augmenting long-acting injectable risperidone with 5 mg/day aripiprazole in patients with hyperprolactinemia (J. Clin. Psychopharmacol. 2013;33:538-41). The open-label trial continued for 3 months.
Of the 13 patients, 12 had a significant decrease in prolactin level by the end of the first month, with two patients reaching normal levels. The decrease was maintained in the eight patients who continued through the end of the study. Again, there were no clinical adverse effects of adding the medication.
While lowering prolactin is generally safe, Dr. Carlson did caution against it in one circumstance – a woman who is trying to breastfeed. "If someone is post partum and trying to nurse, this is not the time to give aripiprazole, because she will have difficulty maintaining milk production."
Dr. Carlson disclosed that he has received research support from numerous pharmaceutical companies.