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Schizophrenia’s silent epidemic: Iatrogenic sexual dysfunction



– Many psychiatrists have no inkling of how often the antipsychotic agents they prescribe cause hyperprolactinemia-related sexual dysfunction, or the serious negative consequences these common side effects have on quality of life and treatment adherence, Ángel L. Montejo, MD, PhD, declared at the annual congress of the European College of Neuropsychopharmacology.

Psychiatrists are largely uninformed about these matters, because for the most part, they avoid talking with their schizophrenia patients about their sexual activity or inquiring about sexual dysfunction. And they don’t perform the physical examinations that might reveal tell-tale stigmatizing gynecomastia or galactorrhea, according to Dr. Montejo, professor of psychiatry at the University of Salamanca (Spain).

Dr. Angel L. Montejo, professor of psychiatry at the University of Salamanca (Spain) Bruce Jancin/Frontline Medical News

Dr. Angel L. Montejo

He was lead author of a recent Spanish multidisciplinary consensus report on iatrogenic hyperprolactinemia secondary to antipsychotic agents. The expert panel comprised psychiatrists, endocrinologists, oncologists, rheumatologists, and internists (Front Neuroendocrinol. 2017 Apr;45:25-34).

The consensus report includes recommendations for the detection and management of the full range of manifestations of iatrogenic hyperprolactinemia, including osteoporosis and hip fracture, hypogonadism, premature menopause, cardiovascular disease, breast and endometrial cancer, and immunologic disorders.

However, the most common expression of antipsychotic-related hyperprolactinemia is sexual dysfunction, and that’s what Dr. Montejo focused on. This is an issue that directly relates to clinical outcomes. The literature shows that roughly 36% of male and 19% of female schizophrenia patients either stop taking their medication because of its sexual side effects, which include decreased libido, erectile difficulty, vaginal dryness, and anorgasmia, or are thinking about doing so. At least two in three schizophrenia patients engage in some sort of sexual activity. Sixty percent of patients say that having a sexual life is important to them. Yet 73% of psychiatrists in one survey indicated that they don’t interview their patients about their sexual relations.

“If sexual activity is good for you, why isn’t it good for your patients? We’re talking about love, about human relationships. Having a sexual and emotional life can help patients get the best outcomes,” said Dr. Montejo.

“If you don’t ask about sexual dysfunction, your patients won’t tell. Therefore, you may not see it, but your patients will experience it. They know the difference between their sexual life before treatment and during treatment,” he continued.

The incidence of sexual dysfunction in patients on antipsychotic therapy is a function of the agent they are on. Iatrogenic hyperprolactinemia is a consequence of intense blockade of dopamine D2 receptors. The most potent antipsychotic dopamine D2 receptor antagonists are risperidone and paliperidone, followed by haloperidol and most other first-generation antipsychotics.

A normal prolactin level is less than 25 ng/mL in women and less than 20 ng/mL in men. Endocrinologists divide hyperprolactinemia into three categories: mild hyperprolactinemia is a level of 25-50 ng/mL, moderate is 51-100 ng/mL, and severe is anything over 100 ng/mL.

In one study, 44% of patients on oral risperidone at a mean dose of 4.9 mg/day had moderate and 23% had severe hyperprolactinemia; in patients on the injectable long-acting formulation of the drug at a mean dose of 46.2 mg/month, 23% of patients had moderate and 31% had severe hyperprolactinemia. Patients on oral paliperidone at a mean dose of 8.5 mg/day had a 45% prevalence of moderate and an 18% rate of severe hyperprolactinemia, while 40% of those on long-acting injectable paliperidone at a mean of 104 mg/month had moderate and another 40% had severe hyperprolactinemia.

Sixty to 80% of patients on risperidone or paliperidone experience hyperprolactinemia-induced sexual dysfunction. At the other end of the spectrum is the prolactin-sparing antipsychotic aripiprazole, which is associated with sexual dysfunction in about 5% of treated patients. In a meta-analysis, the other prolactin-sparing antipsychotics included ziprasidone, with a 10% rate, quetiapine at 12%, and olanzapine with a 20% rate.

Screening tests for sexual dysfunction

Psychiatrists who are uncomfortable asking patients about sexual dysfunction or don’t want to take the time to do so have other good options. Four easy-to-use, validated instruments are available for free online: the four-question Arizona Sexual Experiences Scale; the Change in Sexual Function Questionnaire, or CSFQ; the Sex Effects Scale, or SexFX; and the Psychotropic-Related Sexual Dysfunction Questionnaire (PRSexDQ-SALSEX).

Managing antipsychotic-induced hyperprolactinemia

The Spanish consensus panel recommended that before psychiatrists prescribe an antipsychotic, they should always explain to patients their risk of antipsychotic-related hyperprolactinemia and make an assessment of personal and family history of risk factors for its possible downstream consequences, including osteoporosis and cancer. And Dr. Montejo stressed that clinicians must “always, always, always” get a baseline serum prolactin measurement, to be repeated after increasing the drug dosage, changing antipsychotics, or upon development of symptoms of hyperprolactinemia.

When a patient’s prolactin level climbs above 50 ng/mL or symptoms of hyperprolactinemia arise, the preferred strategy is to switch to a prolactin-sparing antipsychotic. Most of the alternative options are unsatisfactory. For example, waiting for a sexual side effect to pass is pointless, because it won’t happen spontaneously. A drug holiday undermines compliance. Reducing the antipsychotic dose increases the risk of relapse.

And as for prescribing adjunctive dopamine agonist therapy, well: “Adding a dopamine agonist is not the first step. It should be one of the last steps, because it greatly increases the odds of worsening psychosis,” Dr. Montejo said.

If switching to a different antipsychotic is not possible, the expert panel recommended add-on aripiprazole, accompanied if possible by a downward dose adjustment of the offending antipsychotic. This is an effective way to lower elevated serum prolactin levels.

It’s appropriate to order a lumbar spine and proximal femur bone mineral density measurement in patients on antipsychotic agents if they are older than age 65, have had amenorrhea for at least 6 months, experienced menopause before age 35, have a body mass index below 19 kg/m2, or are experiencing any symptoms of hyperprolactinemia, including sexual dysfunction, according to the Spanish consensus algorithm.

Dr. Montejo reported receiving research grants from and/or serving as a consultant to more than half a dozen pharmaceutical companies.

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