Sexual Dysfunction in Schizophrenia

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1		Elyse M. Cornett	+ 1989 word(s)	1989	2021-12-29 10:35:04	\|
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This entry is adapted from the peer-reviewed paper 10.3390/psychiatryint3010003

Psychiatric disorders, in general, have a high prevalence of sexual problems, whether from the psychopathology of the disorder itself, pre-existing or co-morbid sexual disorder or from side effects of the treatment for mental disorders. Many patients report an already existing sexual dysfunction at the onset of diagnosis. The risk association for developing sexual dysfunction in patients with schizophrenia includes antipsychotic use and resulting hyperprolactinemia, age, gender, and disease severity. Medication side effects lead to nonadherence, and relapses lead to structural changes in the brain, treatment resistance, and worsening of symptoms. Findings in certain studies propose serum prolactin and thyroid-stimulating hormone measurement as a tool for assessing patients with schizophrenia for sexual dysfunction. Regarding specific symptoms, females especially reported decreased desire at baseline and galactorrhea after treatment.

antipsychotics sexual dysfunction prolactin thyroid-stimulating hormone schizophrenia

1. Introduction

Psychiatric disorders have a high prevalence of sexual problems, whether from the psychopathology of the disorder itself, pre-existing or co-morbid sexual disorder, or from side effects of the treatment for mental disorders ^[1]^[2]. In schizophrenia, negative symptoms (anhedonia) can attribute to decreased sexual functioning ^[1]^[3]. Males and females with schizophrenia have reported sexual dysfunction in the form of decreased sexual desire, decreased sexual arousal (erectile dysfunction, priapism, diminished vaginal lubrication), anorgasmia, ejaculation, and menstrual disturbance, galactorrhea, or gynecomastia ^[3]. A study conducted by Serretti et al. showed that 16–60% of patients using antipsychotics reported sexual dysfunctions ^[3]^[4]. Antipsychotic medications may cause decreased sexual desire, erectile dysfunction, anorgasmia, and delayed or retrograde ejaculation ^[5]^[6]. This is in accordance with what is reported by patients with Schizophrenia as stated earlier in the paragraph. Patients with schizophrenia consider sexual problems to be very important related to the effects on quality of life and adherence to medication. Discussing sexual problems with a provider is sometimes difficult for patients. Physicians should be aware of this and initiate conversations about their patient’s sexual histories and expectations for their sexual life before prescribing antipsychotic medications ^[2]^[3]. The sexual side effects of medications may be the reason many people discontinue them.

2. Clinical Studies about Sexual Dysfunction in Schizophrenia

Recent clinical studies have attempted to better understand sexual dysfunction in patients with schizophrenia. Studies typically evaluate the degree of sexual dysfunction through self-administered questionnaires filled out by patients with schizophrenia. The commonly used Arizona Sexual Experience Scale (ASEX), for example, measures sexual function through a 5-item scale which explores strength of sexual drive, ease of sexual arousal, penile erection or vaginal lubrication, the ability to reach orgasm, and satisfaction with orgasm in the past week ^[7]^[8]^[9]. Other measurement tools for sexual dysfunction include the Psychotropic-Related Sexual Dysfunction Questionnaire, the Changes in Sexual Functioning Questionnaires (CSFQ-14) and the Udvalg for Klinsike Undersogelser (UKU). Some researchers conducting clinical studies have also developed their own questionnaires that explore similar factors of sexual functioning ^[10]^[11]^[12]^[13]. The 2011 Japanese study evaluating sexual dysfunction in schizophrenic patients used a custom 7-item questionnaire called the Nagoya Sexual Function Questionnaire (NSFQ) in order to better tailor the style of questions asked to the sensitivities of Asian patients with schizophrenia, who are often culturally more hesitant to discuss matters of sexual functioning with their physicians. NSFQ questions were designed and intended to be less invasive and more likely to elicit a response from patients assessed ^[14]. Despite the range of tools used to measure sexual functioning, studies consistently find a significant proportion of sexual dysfunction among schizophrenic patients. Sexual dysfunction is estimated to affect a significant number of patients suffering from and treated for schizophrenia ^[11]^[8]^[13] with prevalence estimates ranging from around 30% to as high as 83% in different studies ^[7]^[10]^[12].

Although the precise mechanism of the development of sexual dysfunction is unknown, the relationship between several variables believed important in the cause of sexual dysfunction in patients with schizophrenia have been evaluated in cross-sectional studies. These variables include prolactin levels, quality of life, antipsychotic medication, gender, and disease severity. Although these studies do not always completely agree in their findings, there have been some significant correlations shown across multiple studies with regards to certain variables, most notably gender, antipsychotic use, and prolactin levels.

Hyperprolactinemia has been established as a well-known side effect of antipsychotic medications used to treat schizophrenia, due to the disruption of the tuberoinfundibular pathway via dopamine blockade. In particular, risperidone/paliperidone and olanzapine have the most profound impact on prolactin levels ^[12]^[13]. In contrast, the second-generation antipsychotic aripiprazole (APZ) has been associated with decreased prolactin levels and is thought to stabilize D2 receptor-mediated neurotransmission through non-excessive receptor blockade ^[12]. A study by Kirino et al found a decrease or resolution of hyperprolactinemia in patients treated for schizophrenia with APZ monotherapy or with polytherapy including APZ. Serum prolactin was additionally found significantly higher in patients experiencing at least one symptom of sexual dysfunction compared to those who did not ^[13]. It has not been clear whether high levels of prolactin develop from causes other than antipsychotic use, nor has the degree to which sexual dysfunction is directly caused by increased serum prolactin been completely understood. Examining these questions, During et al compared prolactin levels and sexual functioning in patients with schizophrenia at baseline and after 6 months of antipsychotic treatment ^[10]. This study found sexual dysfunction in 68% of patients with schizophrenia at baseline and 65% after treatment. After treatment with D2/3 receptor blockade amisulpride, all patients developed hyperprolactinemia. Only 11% of males and 10% of females at baseline had increased prolactin levels ^[10]. Recent clinical studies show the importance in considering the relationship between hyperprolactinemia and sexual dysfunction in schizophrenia patients and suggest that monitoring baseline and follow-up levels of prolactin in patients may allow for better management of sexual dysfunction in patients, especially in those treated with antipsychotics known to cause hyperprolactinemia ^[10]^[12]^[13].

Studies have also found a higher incidence of sexual dysfunction in female patients ^[10]^[12]^[13]. For example, Düring et al. found high levels of sexual dysfunction in females and males both before and after antipsychotic treatment. After treatment, however, sexual dysfunction in females was significantly higher compared to males ^[10]. Increased levels of sexual dysfunction typically coincide with pronounced serum prolactin levels in female patients. Kikuchi et al. as well as Kirino et al. found that a proportion of female patients experienced particularly high levels of prolactin (>100 ng/mL) ^[14]^[13]. These patients were found in the Kirino study to experience irregular menstruation or amenorrhea ^[13].

Disease severity, quality of life, and age have also been studied for their association with sexual dysfunction in patients with schizophrenia. Older age has also been correlated with increased incidence of sexual dysfunction ^[8]^[9], while results studying disease severity and quality of life have shown mixed results. Martin et al. found no relation between severity of schizophrenia and sexual dysfunction, while Zhang et al. found increased disease severity scores, particularly scores impacted by increased negative symptoms, to be an independent factor for the development of sexual dysfunction ^[10]^[12]. Ghormode et al. and Huang et al. found that patients with schizophrenia experienced more sexual dysfunction but found no differences in social relationships measured quality of life questionnaires compared to controls ^[8]^[9]. Contrastingly, the Ethiopian study found that sexual dysfunction was associated with a poorer quality of life in patients with schizophrenia, hypothesizing that this effect is due to the effect of the disease has on a patient’s ability to maintain personal intimate relationships ^[11]. Additionally, patients in this study who were unmarried, widowed, or divorced, were 3–4× more likely to develop sexual dysfunction ^[11].

3. Treatment of Sexual Dysfunction in Schizophrenia

Many of the studies reviewed looked at the treatment of the increased prolactin levels that are caused by antipsychotic therapy. One such study looked at the treatment of hyperprolactinemia using bromocriptine vs. herbal medicine in patients with risperidone-induced hyperprolactinemia ^[15]. Hyperprolactinemia was diagnosed with serum prolactin levels > 50 mug/L. The subjects were randomized to receive Peony-Glycyrrhiza Decoction (45 g/day) followed by bromocriptine (5 mg/day) or bromocriptine followed by Peony-Glycyrrhiza Decoction. Sexual dysfunction was defined as either experiencing oligomenorrhea or amenorrhea. The severity of psychotic symptoms, adverse events, serum prolactin levels, estradiol, testosterone, and progesterone levels were examined at baseline and endpoint ^[16]. The authors concluded that Peony-Glycyrrhiza Decoction showed fewer adverse events, and significantly decreased prolactin levels without worsening of psychosis or other hormone levels.

Many studies have looked at the use of aripiprazole to decrease the hyperprolactinemia associated with antipsychotic treatment. One study looked at the addition of 5 mg of aripiprazole to treat hyperprolactinemia associated with the use of an injection form of risperidone ^[17]. This was an open, uncontrolled trial of 13 patients treated with injectable risperidone. Twelve of the thirteen patients showed a decrease in serum prolactin levels and the eight that continued treatment for two more months continued to show a decrease in prolactin levels ^[17]. Adverse effects of aripiprazole were transient and mild.

Another Japanese study looked at the use of adjunctive aripiprazole to treat hyperprolactinemia. They found that prolactin levels at week 4 and later was significantly lower than at the beginning of the study, Sexual dysfunction was also significantly improved, which was measured by erectile dysfunction in males and menstrual irregularity ^[15]. The problem with these studies, however, is their limited sample size and more studies would need to be done to validate the use of aripiprazole in the treatment of hyperprolactinemia and sexual dysfunction in patients using other antipsychotics.

4. Conclusions

Schizophrenia is a chronic illness that, in most cases, is diagnosed early in a patient’s life and has the potential to negatively affect their personal and social life. Sexual dysfunction has been shown to affect a significant portion of schizophrenic patients and is associated with a poorer quality of life due to the reduced ability to maintain personal intimate relationships. This dysfunction may be due to the disease itself or may come as a result of pharmacologic treatment. There is a lack of understanding that this can happen at baseline in a patient with a psychotic disorder. A comprehensive review of the patient’s sexual health should be done whether it be by a primary care physician, psychiatrist, or clinical psychologist. Patients may have their relationships affected by this and studies have shown that it leads to a decreased quality of life. Patients who have psychotic disorders may want a family in the future and this is a hinderance to that desire. This could lead to medication non-adherence which will lead to further psychotic breaks and more problems down the road. It can start to be avoided if the clinician thinks about sexual dysfunction in patients with this type of psychiatric condition and screens for it.

Many patients report an already existing sexual dysfunction at the onset of diagnosis. The risk association for the development of sexual dysfunction in patients with schizophrenia includes antipsychotic use and resulting hyperprolactinemia, age, gender, and disease severity. First generation antipsychotics have been linked to higher levels of prolactin elevation when compared to the atypical antipsychotics. It is difficult to determine whether sexual dysfunction is due to the disease or from pharmacologic therapy. More studies need to be done to better understand the relationship between these factors. Limitations of this manuscript include that it is not a systematic review or meta-analysis but the hope of the authors is that it can be a narrative guide to clinicians who are navigating this rocky terrain.

Since sexual dysfunction can impact a patient’s quality of life and affect treatment adherence, it is important for physicians to be aware and monitor patients for symptoms. Strategies to combat this have focused on other pharmacologic therapies or biopsychosocial therapies. Sexual dysfunction has been treated with other drugs such as PDE inhibitors, but efficacy has been shown to be poor in those with chronic illness. The use of coping strategies may prove to be an important approach for dealing with these issues. However, more studies need to be done to show the effectiveness of this approach. Medication noncompliance remains an issue with schizophrenic patients. The side effect profile of antipsychotics can be a hinderance to consistency and may cause patients to discontinue treatment. It is important for physicians to be aware of these side effects so that they may address them.

References

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