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Medication–induced hyperprolactinemia is more common than you might think and it can produce detrimental long-term health sequelae.  In this podcast, we will review the work-up and management of this common side effect.

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Published On: 10/31/22

Duration: 9 minutes, 16 seconds

Referenced Article: “Psychiatric Medication–Induced Hyperprolactinemia,” The Carlat Hospital Psychiatry Report, July 2022

Victoria Hendrick, MD, and  Prabhjot Gill, BS, have disclosed no relevant financial or other interests in any commercial companies pertaining to this educational activity.

Dr. Hendrick: Most patients on antipsychotic medications have prolactin levels that are significantly higher than normal (>25 ng/mL for nonpregnant women and >16 ng/mL for men). You have most likely heard about missed menstrual cycles or galactorrhea (milky nipple discharge) from your female patients, while your male patients have probably complained of gynecomastia (enlarged breasts), impotence, and low sexual desire after taking antipsychotic medications. These are common manifestations of hyperprolactinemia and certain antipsychotics are more likely to raise prolactin levels, especially paliperidone, risperidone, and many of the first-generation agents.

In this podcast, we will review the work-up and management of medication–induced hyperprolactinemia. 

Welcome to The Carlat Psychiatry Podcast

This is a special episode from The Carlat Hospital Psychiatry Report.

I’m Dr. Victoria Hendrick, the Editor-in-Chief of The Carlat Hospital Psychiatry Report, and a clinical professor at the David Geffen School of Medicine at UCLA. I’m also the director of inpatient psychiatry at Olive View — UCLA Medical Center.

Prabhjot Gill: And I’m Prabhjot Gill. I graduated from UC Santa Cruz with a BS degree in neuroscience, and I’m a content-coordinator at Carlat Publishing. I write CME questions, podcast scripts, and I edit podcasts too. I’m currently applying to psyd programs and I’ll be joining Dr. Hendrick on this podcast.

So Dr. Hendrick, why do so many antipsychotics raise prolactin levels?

Dr. Hendrick: Normally, dopamine inhibits prolactin synthesis and secretion. Since antipsychotics block dopamine receptors, the brakes that dopamine puts on prolactin are removed, leading to higher prolactin levels. First-generation antipsychotics produce more severe hyperprolactinemia (two to three times the upper limit of reference range). In contrast, second-generation antipsychotics usually produce a milder prolactin increase due to their lower affinity for the D2 receptor, with the exceptions of paliperidone and risperidone (which, especially at higher doses, increase prolactin similarly to first-generation antipsychotics).

Prabhjot Gill: Are there any other medications that can cause hyperprolactinemia?

Dr. Hendrick: Yes! You might be surprised to know that several antidepressants also cause hyperprolactinemia, particularly clomipramine, mainly via serotonergic pathways. This effect is mostly mild and rarely symptomatic, although occasionally female patients will report galactorrhea or missed menstrual cycles. 

Prabhjot Gill: Wow, that’s really interesting. Should clinicians be worried about hyperprolactinemia?

Dr. Hendrick: Well, it’s easy to overlook HPRL because its symptoms are not readily apparent and patients are often embarrassed to tell us about them. However, ­prolactin-related side effects, if unaddressed, significantly increase medication nonadherence. Hyperprolactinemia causes hypogonadism by suppressing ­gonadotropin-releasing hormone, resulting in menstrual irregularities, infertility, and decreased libido in women. Men experience erectile dysfunction, reduced libido, impaired spermatogenesis, gynecomastia, anemia, decreased muscle mass, and low energy levels. Galactorrhea is a common manifestation of hyperprolactinemia in ­pre-menopausal women while it is less frequent in ­post-menopausal women and rarely occurs in men.

One of the most significant long-term consequences of sustained hyperprolactinemia is a loss of bone density. Many studies have reported significantly higher rates of osteoporosis and bone fractures in patients taking antipsychotic medications for schizophrenia. 

Prabhjot Gill: How should clinicians approach diagnosing patients with hyperprolactinemia?

Dr. Hendrick: We recommend getting a baseline prolactin level before patients begin a psychiatric medication that is likely to cause hyperprolactinemia. Check this level again in three months, but sooner if you see symptoms of hyperprolactinemia. A prolactin level can be drawn at any time of day, but a few things can artificially cause a transient rise in prolactin, including exercise, nipple stimulation, and even the stress of getting stuck by a needle.

Prabhjot Gill: What do you do if your patient’s prolactin level is elevated? 

Dr. Hendrick: A first step is to rule out an elevated level of macroprolactin, which is a physiologically inactive form of prolactin. While few clinicians have heard about this, studies show that macroprolactin causes a false HPRL diagnosis in about 19% of cases. Unfortunately, not all labs offer this test. 

Assuming that no macroprolactin is present, your next step is to exclude other causes of increased prolactin, such as pregnancy, hypothyroidism, and kidney or liver dysfunction. A rare cause of high prolactin is a pituitary tumor, which typically presents with headaches and vision changes. If you stop the patient’s antipsychotic and the hyperprolactinemia persists, consider consulting an endocrinologist, who will likely order an MRI or CT scan to rule out a pituitary tumor.

Prabhjot Gill: What about management strategies? What steps should clinicians take when a patient has asymptomatic hyperprolactinemia versus symptomatic hyperprolactinemia?

Dr. Hendrick: If your patient has asymptomatic HPRL, you don’t need to do anything. Continue the antipsychotic and check prolactin annually.

For patients who have symptoms, switch to a different agent with “prolactin-sparing” potential, such as aripiprazole, clozapine, or ziprasidone. Another option is to decrease the dose, as psychiatric medication–induced HPRL is usually dose related—but patients’ psychiatric symptoms might not respond well to lower antipsychotic doses. A nice psychopharm trick to have up your sleeve is adding low-dose aripiprazole (5–15 mg/day) as an adjunctive therapy. Aripiprazole reduces prolactin levels due to its partial agonistic activity at D2 receptors. Several studies have found this strategy effective. 

However, if you’ve tried all the above and the HPRL continues, you can try prescribing a dopamine agonist such as cabergoline or bromocriptine. Be mindful that doing so will mean you are working at odds with the dopamine-blocking properties of the antipsychotic, and the patient’s psychiatric symptoms could worsen. For female patients, another option is to add a birth control pill, which will replenish estrogen that has been lowered by the prolactin. A more direct approach is using hormone replacement therapy—though this would usually be prescribed by the patient’s primary care physician or OB-GYN. 

Prabhjot Gill: Overall, remember: don’t ignore hyperprolactinemia! Switch meds, add aripiprazole, add a dopamine agonist, or encourage hormone replacement therapy. Your patients will be happy you went the extra mile!

Dr. Hendrick: The newsletter clinical update is available for subscribers to read in The Carlat Child Psychiatry Report. Hopefully, people will check it out. Subscribers get print issues in the mail and email notifications when new issues are available on the website. Subscriptions also come with full access to all the articles on the website and CME credits. 

Prabhjot Gill: And everything from Carlat Publishing is independently researched and produced. There’s no funding from the pharmaceutical industry. 

Dr. Hendrick: Yes, the newsletters and books we produce depend entirely on reader support. There are no ads and our authors don’t receive industry funding. That helps us to bring you unbiased information that you can trust. 

Prabhjot Gill: And don’t forget, you can now earn CME credits for listening to our podcasts. Just click the link in the description to access the CME post-test for this episode.

As always, thanks for listening and have a great day!