The Sexual Side-Effects of Antipsychotics

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Effects of Antipsychotics on Prolactin and Sexual Health

The effects of conventional antipsychotics on prolactin are well known. Over 25 years ago, the sustained elevation of serum prolactin to pathological levels by conventional antipsychotics was demonstrated by Meltzer and Fang. The most important factor regulating prolactin is the inhibitory control exerted by dopamine. Any agent that blocks dopamine receptors in a non-selective manner can cause elevation of serum prolactin. Most studies have shown that conventional antipsychotics are associated with a two-to ten-fold increase in prolactin levels.

Prolactin is a hormone in the blood that helps to produce milk and is involved in breast development. However, increased prolactin can lead to a decrease in libido when it is not needed.

The increase in prolactin that occurs through the use of conventional antipsychotics develops over the first week of treatment and remains elevated throughout the period of use. Once treatment stops, prolactin levels return to normal within 2-3 weeks.

In general, second-generation atypical antipsychotics produce lower increases in prolactin than conventional agents. Some agents, including olanzapine (Zyprexa), quetiapine (Seroquel), ziprasidone (Geodon) and clozapine (Clozaril) have been shown to produce no significant or sustained increase in prolactin in adult patients. However, in adolescents (age 9-19 years) treated for childhood-onset schizophrenia or psychotic disorder, it has been shown that after 6 weeks of olanzapine treatment prolactin levels were increased beyond the upper limit of the normal range in 70% of patients.

Second-generation antipsychotics that have been associated with increases in prolactin levels are amisulpride, zotepine and risperidone.

The most common clinical effects of hyperprolactinaemia (high prolactin levels) are:

In Women:

• anovulation
• infertility
• amenorrhoea (loss of period)
• decreased libido
• gynaecomastia (swollen breasts)
• galactorrhoea (abnormal breast milk production)

In Men:

• decreased libido
• erectile or ejaculatory dysfunction
• azoospermia (no sperm are present in the ejaculate)
• gynaecomastia (swollen breasts)
• galactorrhoea (occasionally) (abnormal breast milk production)

Less frequently, hirsutism (excessive hairiness) in women, and weight gain have been reported.

Antipsychotics and Sexual Dysfunction Sometimes Tough to Link

Sexual function is a complex area that includes emotions, perception, self-esteem, complex behavior and the ability to initiate and complete sexual activity. Important aspects are the maintenance of sexual interest, the ability to achieve arousal, the ability to achieve orgasm and ejaculation, the ability to maintain a satisfying intimate relationship, and self-esteem. The impact of antipsychotics on sexual functioning is difficult to evaluate, and sexual behavior in schizophrenia is an area in which research is lacking. Data from short-term clinical trials may greatly underestimate the extent of endocrine adverse events.

One thing we do know is that drug-free patients with schizophrenia have lower sexual libido, decreased frequency of sexual thoughts, a decreased frequency of sexual intercourse and higher requirements for masturbation. Sexual activity was also found to be reduced in patients with schizophrenia compared with the general population; 27% of schizophrenia patients reported no voluntary sexual activity and 70% reported having no partner. While untreated schizophrenia patients exhibit decreased sexual desire, neuroleptic treatment is associated with restoration of sexual desire, yet it entails erectile, orgasmic and sexual satisfaction problems.

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Atypical antipsychotics are also known to contribute to the development of hyperprolactinaemia. Data for Zyprexa (olanzapine), Seroquel (quetiapine) and Risperdal (risperidone) are published in the Physician's Desk Reference (PDR); a useful reference source since it reports incidence rates for most adverse effects, including EPS, weight gain, and somnolence. The PDR states that “olanzapine elevates prolactin levels, and a modest elevation persists during chronic administration.” The following adverse effects are listed as “frequent”: decreased libido, amenorrhoea, metrorrhagia (uterine bleeding at irregular intervals), vaginitis. For Seroquel (quetiapine), the PDR states, “an elevation of prolactin levels was not demonstrated in clinical trials”, and no adverse effects relating to sexual dysfunction are listed as “frequent”. The PDR states that “Risperdal (risperidone) elevates prolactin levels and the elevation persists during chronic administration.” The following adverse effects are listed as “frequent”: diminished sexual desire, menorrhagia, orgastic dysfunction, and dry vagina.

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Last updated: 10/05

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