Loss of Libido in a Woman With Schizophrenia

In a patient like Ms. J in the vignette (a composite case), lack of libido could be the result of a relationship problem, or it could be caused by a medical problem, possibly one connected to schizophrenia and its treatment. As is often the case, it is probably the result of a combination of factors.

Low libido is part of a triad of symptoms that together constitute sexual dysfunction in women. The other two symptoms are lack of vaginal lubrication during sexual activity and difficulty achieving orgasm. The prevalence of sexual dysfunction among all women is estimated to be between 25% and 63%, and is high relative to men (8). The prevalence rises in postmenopausal women, with rates between 68% and 86.5% (9), although personal distress about these symptoms tends to diminish with age (8). In schizophrenia, the rates are higher than in the general population. In a 2003 U.K. survey of schizophrenia patients, 82% of males and 96% of females reported at least one sexual dysfunction (10). The U.K. survey detected no difference in any area of sexual dysfunction between those who did and those who did not have current sexual partners. The dysfunction applied to self-stimulation as well as to interpersonal sex. This is clinically important because, since women with schizophrenia frequently do not have partners, it has been wrongly assumed in the past that sexual function did not matter to them.

Ms. J was referred to her family physician for a physical examination, medication review, and lipid, prolactin, glucose, and thyroid hormone levels. Because of her 5-year history of antipsychotic medication, Ms. J was considered to have an elevated risk for obesity, diabetes, and metabolic syndrome, all three of which are associated with sexual dysfunction in women (11–13).

In the meantime, her psychiatrist engaged the patient in a discussion about the quality of her marital relationship. Ms. J said that in the past her interest in sex had always been closely tied to her wish for children. Currently, she agreed with her husband that one child was sufficient. Her son was having some disciplinary problems at home and at school, and she felt that she and her husband would not be able to cope with a second child. Having come to this decision, her interest in sex had dropped, and neither she nor her husband was happy about it. Depression is a known cause of sexual dysfunction (14), so Ms. J’s psychiatrist questioned her carefully about her mood, her sleep, and her appetite. Ms. J showed no other signs of depression. She had received a promotion at work and was quite pleased with her ability to bring more income to the household.

Since both she and her husband were concerned about her lack of interest in sexual activity, they agreed to a referral to a brief trial of relationship therapy (4, 6). Fifteen randomized controlled trials of psychological treatment in female sexual dysfunction and two other studies that examined both male and female sexual dysfunction have shown significant benefit, although it is not always maintained (15).

Not for the first time, the psychiatrist also talked to Ms. J about lifestyle alterations—diet, exercise, smoking cessation, and abstention from alcohol—because lifestyle factors are potent contributors to sexual dysfunction (5). Alcohol was not hard for Ms. J to give up; neither was smoking. She found dieting and exercise difficult, however, and insisted that she had no time for joining group programs that could be of help.

Her prolactin level turned out to be 55 ng/ml; a pituitary tumor was ruled out by imaging, and attention focused on lowering her prolactin level. Antipsychotic medication is always a prime suspect in sexual dysfunction associated with schizophrenia because untreated patients show significantly less sexual dysfunction than treated patients (16). In most studies, the extent of sexual dysfunction varies with the specific antipsychotic used. Prolactin-raising drugs are usually the ones most associated with sexual dysfunction (40%–60% prevalence in patients using prolactin-raising drugs, compared with 15%–30% in those using prolactin-sparing drugs) (17), although a differential effect on sexual function between prolactin-sparing and prolactin-raising drugs is by no means universal (18). Factors such as obesity, diabetes, metabolic syndrome, schizophrenia itself, and nicotine and alcohol consumption, as well as medications other than antipsychotics, may all confound the association (19). In principle, to bring prolactin levels down, the psychiatrist has three options: to lower the antipsychotic dosage and risk a return of psychotic symptoms; to add a prolactin-lowering drug such as bromocriptine or cabergoline (20) which can also aggravate psychotic symptoms (21); or to switch to an antipsychotic that does not elevate prolactin levels.

Twenty-five open-label noncontrolled studies and six randomized controlled trials of treatment of sexual dysfunction in schizophrenia found that a switch to aripiprazole was the only antipsychotic switch that reliably decreased prolactin levels; a switch to quetiapine was also effective, but not consistently so (6).

A recent Cochrane review on managing sexual dysfunction secondary to antipsychotic therapy (22) concluded that more well-designed investigations of the effects of dose reduction, drug holidays, symptomatic therapy, and antipsychotic switch are needed because current best practice is still uncertain. Psychiatrists do not usually use add-on therapies; they prefer dose reduction or antipsychotic switch. If patients are referred for an endocrinology consultation, however, add-on therapies are often recommended.

In addition to sexual dysfunction, there could be several other reasons to reduce prolactin levels in Ms. J. For one, she experienced both amenorrhea and galactorrhea. More importantly, there was a history of breast cancer in her family, so she herself was potentially at risk. Prolactin has been implicated in some types of breast cancer (23, 24). Prevention of osteoporosis is another reason for lowering prolactin levels (25).

Ms. J and her psychiatrist opted for a switch to aripiprazole, at 30 mg/day. Within 1 week of stopping pimozide and initiating aripiprazole, Ms. J’s prolactin levels were within normal range (26).

In women of reproductive age, the incidence of unwanted pregnancy increases after making such a switch (27, 28), although how often this happens is unknown. The fertility rate of women with schizophrenia appears to have increased over that of the general population of women since the introduction of prolactin-sparing drugs (29), but other factors may have been responsible, and most pregnancies of women with schizophrenia are probably not unwelcome. It is critical, however, for clinicians to realize that a switch from prolactin-elevating to prolactin-sparing antipsychotics may lead to a return to full fertility, which may, on occasion, be both unanticipated and unwanted.

Ms. J was informed of the risk and told that the absence of regular menses was not a guarantee of infertility (30). Her psychiatrist counseled Ms. J and her husband about the pros and cons of various kinds of contraception (31–33), including a long discussion about the risks of the withdrawal method that they were using (one in five women experience pregnancy within a year of typical use [34]). The couple was also instructed on the availability of emergency contraception in case of accident (33). The discussion also covered comparative success rates of the various contraceptive methods, costs, side effects, and relative difficulties of advance planning and equipment maintenance (33). Ms. J’s husband offered to have a vasectomy, but she was against it, thinking that she may still wish to have another child later in life. She did not want anything to do with hormones, worried that there might be interactions with her medication and that there would be side effects. She had heard that some women reacted to contraceptive pills with a loss of libido (35)—precisely what she was trying to overcome. She decided on a nonhormonal IUD, an effective method with few side effects that was both long-term and reversible (33).

Ms. J and her husband spent several joint visits discussing the difficulties of pregnancy and parenting in the context of schizophrenia (36–41). They already knew how difficult it was to maintain child custody in the face of illness (42, 43) because the child protection services had been called in when Ms. J suffered her first episode of psychosis after the birth of her son. Had it not been for the availability of her mother and her mother-in-law at the time, the child may well have been taken away from her and placed in foster care.

A presenting problem such as loss of libido needs to be explored in depth with the patient and inquiries made into its nature, duration, and extent. If an intervention is requested by the patient or contemplated by the clinician, its purposes should be clear. Most decisions involving medication change in schizophrenia require screening tests and a medical workup and subsequent joint decision-making with patient and family members. Some problems will require specialized referrals. Before making a medication change, it is always important to discuss lifestyle modifications—smoking cessation, an exercise program, dietary changes, and withdrawal from alcohol and other drugs of abuse. Before switching medication, clinician and patient may want to consider whether a dosage reduction, drug holidays, or changing the hour of drug ingestion can obviate the problems the patient is experiencing. An add-on therapy or a change to a new medication can be considered next, with the understanding that both can lead to drug interactions and can have unwanted repercussions. In the case of switching from prolactin-elevating to prolactin-sparing medication in women, unwanted pregnancy is an important concern. Effective methods of contraception need to be explored and carefully monitored. In general, clinicians need to be aware of potential unintended effects of new interventions.

Despite the contraceptive advice, Ms. J did become pregnant. This was both a good and a bad outcome. She had overcome the libido problem and was engaging in sex more often than before. She had not, however, invested in the IUD. The choice as to what to do at this juncture was a difficult one, but she decided to terminate her pregnancy. This crucial decision was accompanied by ambivalence and stress, especially because the time period for making it was necessarily limited. Ms. J was fully competent to make the decision, but that is not the case for some women with schizophrenia. Clinicians need to familiarize themselves with methods that facilitate an initially incompetent woman’s decision-making capabilities (repeated discussion, treatment of psychotic symptoms, family and partner involvement, clergy involvement if appropriate, attempts at cognitive remediation) (44, 45). Should competence not return in time, a substitute decision maker must be sought.

Ms. J managed to withstand the stress of the decision and the procedure, and her IUD is now in place. She has returned to her part-time job, and her husband has found employment as well.

The author has served as a medical consultant for Clera, Inc.