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SPECIAL ARTICLE

The impact of severe mental disorders and psychotropic on sexual health and its implications for clinical management

Angel L. Montejo1, Laura Montejo2, David S. Baldwin3 1Department of Nursing and Institute of Biomedicine of Salamanca, Neurosciences Area, University Hospital of Salamanca, Salamanca, Spain; 2Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain; 3Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK

Sexual dysfunction often accompanies severe psychiatric illness and can be due to both the itself and the use of psychotropic treatments. Many sexual symptoms resolve as the mental state improves, but treatment-related sexual adverse events tend to persist over time, and are unfortunately under-recognized by clinicians and scarcely investigated in clinical trials. Treatment-emergent adverse- ly affects quality of life and may contribute to reduce treatment adherence. There are important differences between the various compounds in the incidence of adverse sexual effects, associated with differences in mechanisms of action. with a predominantly serotonergic activity, antipsychotics likely to induce hyperprolactinaemia, and mood stabilizers with hormonal effects are often linked to moderate or severe sexual dysfunction, including decreased , delayed , , and difficulties. Severe mental disorders can interfere with sexual function and satisfaction, while patients wish to preserve a previously satisfactory sexual activity. In many patients, a lack of intimate relationships and chronic deterioration in mental and physical health can be accompanied by either a poor sexual life or a more frequent risky sexual behaviour than in the general population. Here we describe the influence of and antipsychotic medications, of and drugs, and of and mood stabilizers on sexual health, and the optimal management of patients with severe psy- chiatric illness and sexual dysfunction.

Key words: Sexual health, sexual dysfunction, severe mental illness, psychosis, depression, bipolar disorder, antipsychotics, antidepressants, mood stabilizers, quality of life

(World 2018;17:3–11)

Psychosexual medicine and psychiatry are overlapping dis- toms, and adverse effects of some antipsychotics2. People di- ciplines, and there is much interest among psychiatrists in im- agnosed with psychotic disorders often have unmet needs re- proving their theoretical knowledge and clinical skills in ad- lating to sexuality and intimacy, which impact negatively on dressing sexual dysfunction. recovery and the ability to lead a fulfilling life. Psychosis tends Adverse sexual effects are frequent with commonly pre- to be a barrier to the expression of sexuality and intimacy3. scribed psychotropic drugs, such as selective reup- It can be difficult to study sexuality in some cultures. How- take inhibitors (SSRIs) and -raising antipsychotics. ever, a questionnaire study found a high frequency (70%) of Deterioration of libido, and arousal and orgasmic dysfunction sexual dysfunction in female patients with in are frequent disturbances, adversely affecting quality of life. India4. An investigation of sexual dysfunction in Chinese pa- Sexual dysfunction tends to be under-reported and under- tients with schizophrenia found a similar frequency5. A Korean recognized and systematic enquiries are needed to assess the study found that sexual satisfaction was negatively correlated incidence, severity and impairment associated with untoward with length of illness in schizophrenic patients receiving ris- sexual effects of psychotropic drugs. peridone6. Recent developments in the field include recognition of the Despite what many clinicians believe, adequate sexual ex- beneficial effects of a healthy sexual life in patients with severe pression can improve overall well-being, restore confidence mental disorders; the need to incorporate this aspect in assess- and dignity, and allow patients with psychosis to overcome 1 ment and management within routine clinical practice ;a problems such as social disengagement and stigma. A study more in-depth understanding of the adverse effects of psycho- comparing sexual life in patients with psychosis and healthy tropic drugs on sexual life; and more detailed guidelines about controls found that sexual activity improved self-esteem, feel- how to manage sexual dysfunction in these already deeply dis- ings of acceptance and additionally sleep, anxiety and mood advantaged people. in patients in a similar way as in controls7. Sexual relationships were considered highly relevant by the vast majority of pa- tients, who were more concerned about affection and com- PSYCHOSIS AND SEXUAL DYSFUNCTION panionship than physical pleasure. Only 13% were able to maintain a steady partner and only 20% had coital activity, but Influence of psychosis on sexuality more than half believed that sexual life was still important to them. Disturbances in sexual functioning in patients with schizo- Some psychotic patients put their health at risk through phrenia and related disorders may arise from multiple factors, sexually transmitted diseases, including HIV, by not using con- including negative symptoms (apathy, avolition), depressive symp- doms8. This emphasizes the need to systematically evaluate po-

World Psychiatry 17:1 - February 2018 3 tentially risky behaviours in these patients, and provide educa- health providers, shame, cultural difficulties and lack of inter- tion designed to promote safer sexual practices. est by psychiatrists. The extent of sub-optimal communication The presence of psychotic symptoms should not be incom- about sexuality in patients with a psychotic disorder assessed patible with healthy sexual relationships. Whilst not all patients within routine clinical practice is considerable, affecting 50-73% attach the same importance to sexual life, many young patients of those with sexual dysfunction13. Lack of adequate discussion who previously had satisfactory sexual relationships are not is more common in female patients, of whom 80% reported prepared to lose this aspect of interpersonal functioning after not to have discussed sexual function with their diagnosis and start of pharmacological treatment. Many young care providers27. Cross-cultural factors are important, as a re- male patients who drop out from antipsychotic cent survey conducted in India found that the majority (73.2%) report the onset of sexual dysfunction – especially erectile and of professionals did not enquire about sexual problems in rou- orgasm problems in the short term and loss of desire over the tine clinical settings, many admitting that they lacked exper- longer term – as reasons for stopping treatment. tise28. Furthermore, many patients with severe mental illness have received little sexual education, and have insufficient time allowed for the discussion of emotional relationships in Influence of treatment of psychosis on sexuality general. Reliable comparisons between antipsychotics are difficult, Sexual dysfunction is common during short- and long-term due to the wide variety of assessment techniques29. Only six treatment with antipsychotics, and is associated with a consid- questionnaires have been validated to assess sexual dysfunc- erable impact on quality of life in adult and adolescent pa- tion in psychotic patients. Following a systematic review of tients9. Depending on the measurement method, it affects psychometric and other properties, only the Antipsychotics between 38 and 86% of patients10-13, including remitted ones and Sexual Functioning Questionnaire (ASFQ)30,theChanges and those experiencing a first episode of schizophrenia14,15. in Sexual Functioning Questionnaire (CSFQ)31, and the Psycho- Symptoms include decreased desire, difficulties in sexual tropic-Related Sexual Dysfunction Questionnaire (PRSexDQ- arousal; problems with penile , vaginal lubrication SALSEX)32 were found to address all aspects of sexual func- and orgasm; and reduced sexual satisfaction. The most fre- tioning, making them preferable for clinical practice and re- quent complaints in clinical practice include orgasmic and search33. erectile difficulties in the short term and decreased desire in Young men with psychosis consider impairment of sexual the longer term. The most frequent pattern in male patients is function as the most important adverse effect of antipsychotic the combination of lowered libido with , medication affecting treatment adherence34,35. In a US-based which is usually unacceptable16,17. nationwide survey of patients with schizophrenia, side effects Several factors are involved, including blockade of dopami- relating to prolactin and other endocrine disturbance were sig- nergic activity, hyperprolactinemia, and alpha-1 receptor block- nificantly related to lower levels of treatment adherence36. ade18. Hyperprolactinemia and related hypogonadism seems Again, cross-cultural factors are probably important, as an inves- to be strongly implicated in sexual dysfunction, being some- tigation in India, using the PRSexDQ-SALSEX questionnaire, times accompanied by infertility, amenorrhea, gynecomastia found that most patients (91.7%) reported good to fair tolerance and galactorrhoea19,20. Higher plasma prolactin levels are as- ofanysexualsideeffects28. sociated with higher rates of erectile and ejaculatory dysfunc- tion in patients with a first episode of schizophrenia16. Dopamine-blocking and hyperprolactinaemia-inducing anti- Management of treatment-induced sexual dysfunction psychotics such as haloperidol, risperidone, paliperidone and in psychotic patients amisulpride are more likely to be associated with decreased libido and/or arousal difficulties. By contrast, aripiprazole, que- Decreasing the dosage, switching the antipsychotic, add-on tiapine, olanzapine and ziprasidone have been linked to low strategies with a dopamine agonist, addition of aripiprazole, or rates of sexual dysfunction (16-27%) in open studies21,22 and in use of a -5 (PDE-5) inhibitor have all shown meta-analyses23. A lower risk for prolactin elevation and sexual some beneficial effects. dysfunction was found with aripiprazole once-monthly when However, reducing antipsychotic dosage may sometimes en- compared to long-acting paliperidone, this difference being gender relapse, so switching to another antipsychotic medica- associated with a greater improvement in quality of life24. tion may be preferable in managing many patients with Erectile problems with antipsychotic drugs may be specifi- treatment-emergent sexual dysfunction. Switching to aripipra- cally related to endothelial dysfunction linked to decreased zole was found successful in several studies, improving delayed nitric oxide production due to inhibition of endothelial nitric /orgasm in some naturalistic settings37, normalizing oxide synthetase25 and vasoconstriction from beta 2-adrenergic prolactin levels38, and maintaining the clinical efficacy of previ- effects26. ous treatment39. A careful switching protocol is needed to Sexual dysfunction tends to be under-estimated in psychotic avoid the reappearance of troublesome psychotic symptoms40. patients, for several reasons including lack of confidence in Adjunctive aripiprazole reduces antipsychotic-induced hyper-

4 World Psychiatry 17:1 - February 2018 prolactinaemia41 and sexual dysfunction42. When differing strat- selves associated with loss of sexual pleasure and sexual dis- egies were compared, switching to aripiprazole monotherapy satisfaction56,57. But depression can exert adverse effects on all was found superior to the addition of aripiprazole in patients aspects of the sexual response, including the ability to achieve with schizophrenia. Positive results have also been reported af- and maintain penile erection, to attain adequate vaginal lubri- ter switching to quetiapine or ziprasidone in 3 to 6-month pro- cation, and to achieve ejaculation or orgasm58. Most antide- spective studies43,44. pressants can exert unwanted effects on sexual function and A Cochrane review of randomized controlled trials involving satisfaction, but the adverse effects of depression itself (and of patients with schizophrenia and sexual dysfunction found that comorbid mental or physical disorders and concomitant medi- sildenafil can improve erectile function and sexual satisfaction cation) are often overlooked when considering the manage- when compared with placebo, and that switching to olanza- ment of patients with sexual dysfunction associated with anti- pine and quetiapine may have a positive impact on sexual depressant treatment. functioning in male and female patients45. Patients and health professionals can feel embarrassed to A recent multidisciplinary consensus process concluded that mention and discuss sexual symptoms, and consultation and switching an antipsychotic to a non-hyperprolactinaemic one is recognition rates in primary medical care are low51,59,60. Unfor- probably the best way to ameliorate antipsychotic-related sex- tunately, reliance on spontaneous reports of sexual adverse ual dysfunction, with aripiprazole being the first-line option46. events leads to a substantial under-estimate of sexual problems Systematic screening for sexual dysfunction is strongly recom- in depressed patients61,62. Screening and severity question- mended47. Psychosocial interventions – i.e., psychoeducation, naires can facilitate recognition and assessment, but cannot supportive psychotherapy and psychiatric rehabilitation – also fully substitute for a comprehensive but sensitive assessment. play a crucial role, with the restoration of sexual function as an The Arizona Sexual Experiences Scale (ASEX)63, the CSFQ31,the achievable recovery target3. Compounds with a lower frequency PRSexDQ-SALSEX32 and the Sex Effects Scale (SexFX)64 all have of sexual dysfunction should be considered as potential first- adequate key psychometric properties (validity, reliability and line options in psychotic patients with an active and satisfactory sensitivity to change) and have been recommended for assess- sexual life. ing sexual function and satisfaction in depressed patients be- fore and during antidepressant treatment62.

DEPRESSION AND SEXUAL DYSFUNCTION Influence of treatment of depression on sexuality

Influence of depression on sexuality It has proved difficult to accurately identify the incidence of treatment-emergent sexual dysfunction (encompassing both Depressive symptoms are strongly associated with sexual the worsening of pre-existing problems and the development difficulties and dissatisfaction, and screening for depression of new sexual difficulties in previously untroubled patients) has been recommended in patients with sexual dysfunction during antidepressant treatment. Two international studies of and chronic illness48. Conversely, depressed patients should the prevalence of sexual dysfunction in depressed patients be screened for sexual dysfunction49. A longitudinal study undergoing treatment with either an SSRI or serotonin-nor- found the prevalence of sexual problems in depressed individ- adrenaline reuptake inhibitor (SNRI), which both accounted uals to be approximately twice the prevalence in controls (50% for self-reported sexual problems before starting treatment vs. 24%)50. and the potential adverse effects of concomitant medication, Recurrent depressive disorder seems especially associated found that 27-65% of female and 26-57% of male patients with sexual problems. For example, the US Study of Women’s experienced either a worsening of pre-existing difficulties or Health Across the Nation found that women with recurrent the emergence of new sexual difficulties in the early weeks of depressive episodes (but not those who experienced only a treatment65,66. single episode) were more likely to report problems in sexual An early meta-analysis which included studies with differ- arousal, physical pleasure and emotional satisfaction, when ing designs (incorporating open-label, double-blind, cross-sec- compared to controls51. The Netherlands Mental Health Sur- tional and retrospective investigations) found that “treatment- vey and Incidence Survey-2 found that the presence of 12- emergent sexual dysfunction” was no more common with the month mood disorders was associated with a significantly antidepressants agomelatine, amineptine, , moclo- lower likelihood of reported sexual satisfaction52. bemide, or than with placebo. All oth- Depression affects mood, energy, interest, capacity for plea- er antidepressants were significantly more likely than pla- sure, self-confidence and self-esteem, so it should be expected cebo to be associated with “sexual dysfunction” (as a unitary that depression lowers sexual interest and satisfaction; this ef- category), and nearly all were significantly more likely than fect seems more marked in younger patients53. Depressive placebo to be associated with dysfunction in each phase of the symptoms commonly coexist with anxiety symptoms, which sexual response67. Bupropion appears associated with a signifi- are also associated with reported sexual difficulties and dissatis- cantly lower rate of treatment-emergent sexual dysfunction faction54,55, and with obsessive-compulsive symptoms, them- than the SSRIs , fluoxetine, or sertra-

World Psychiatry 17:1 - February 2018 5 line68, which may reflect the predominantly noradrenergic- “psychogenic” erectile dysfunction, when prescribed at higher dopaminergic mechanism of action of that drug69. daily dosage (150-200 mg)90. A second meta-analysis, of 58 randomized controlled trials Many patients experience treatment-emergent sexual dys- and five observational studies, found only minor differences function whilst taking an antidepressant68, but in others the between most antidepressants, although there were relative dis- reduction of depressive symptoms through successful treat- advantages for paroxetine and venlafaxine, and relative advan- ment can be accompanied by reported improvements in sex- tages for bupropion70. A systematic review of the relative efficacy ual desire and satisfaction91,92. Improvement in sexual func- and tolerability of mirtazapine and comparator antidepressants tion appears more common among patients who respond to found the former to be less likely than other antidepressants to antidepressant treatment93. cause adverse sexual effects71, possibly reflecting its antagonist The proportion of patients who stop treatment because of effects at alpha-2 adrenergic and 5-HT2C receptors72. sexual problems is not established94,95, nor is the time course Some novel antidepressants may have a relatively low pro- of sexual dysfunction in patients who continue with antide- pensity for adverse effects on sexual function73. Randomized pressant treatment96. controlled trials with agomelatine suggest it has fewer adverse effects on sexual functioning than some other antidepressants, Management of treatment-induced sexual dysfunction in which is probably due to its antagonist effects at the 5-HT2C depressed patients receptor, rather than the agonist effects at melatonin recep- tors74-77, although the absence of effects on nitrergic relaxation Many interventions have been proposed for managing pa- of corpus cavernosum smooth muscle may also be relevant78. tients who report sexual dysfunction associated with antide- Vilazodone appears to have a low incidence of spontaneously pressants, but there are limited randomized controlled data reported adverse effects on sexual function, which may be re- evaluating the effectiveness and acceptability of psychological lated to partial agonist effects at the 5-HT1A receptor: it does and pharmacological interventions97, and no approach can be not differ from placebo in improvement of sexual function dur- considered “ideal”98,99. ing acute treatment of major depressive episodes, and the When patients are concerned to preserve usual sexual func- “number needed to harm” for sexual adverse effects has been tioning, choosing an antidepressant thought to have fewer sex- estimated as 7 in men and 23 in women79-81. Treatment with ual adverse effects is reasonable, when other considerations the novel “multimodal” antidepressant vortioxetine is associ- allow. However, some of these antidepressants have other side ated with a low incidence of reported adverse effects on sexual effects, limited availability, or questionable efficacy. Sexual function in men (3-5%) and women (1-2%), which may relate side effects of some antidepressants may be dose-related, so to its antagonist effects at the 5-HT3 receptor, and to indirect reduction in daily dosage is commonly adopted as a first-line effects in increasing the availability of dopamine and norad- approach to management100. However, dosage reduction may renaline82. contribute to depressive symptom relapse, and should only be Risk factors for developing sexual dysfunction during anti- considered when patients have achieved full remission, and depressant treatment include male gender, older age, lower after satisfactory completion of continuation treatment. Regu- academic achievement, absence of full-time employment, lar brief interruptions of treatment (so-called “drug holidays”) physical ill-health, multiple drug treatment, and troubled 101 interpersonal relationships. Inter-individual variation in phar- have been proposed , but sexual function will improve in macokinetic parameters may be important, as “poor metabo- only a proportion of patients and with only some antidepres- lizer” status for cytochrome P450 2D6 contributes to sexual sants: depressive symptoms may worsen, and troublesome dis- dysfunction with paroxetine83,84, as does a genetic variation in continuation symptoms can emerge, making this approach po- 101 P-glycoprotein which affects transfer of paroxetine across the tentially hazardous . blood-brain barrier85. Many adjuvant interventions have been proposed for reliev- Not all sexual effects of antidepressants are unwanted in all ing sexual dysfunction associated with antidepressants, but few patients. Although behavioural approaches to premature ejac- have been subjected to rigorous evaluation. Randomized pla- ulation are effective in most patients86, many men (including cebo-controlled trials provide evidence of possible efficacy for 102 103 those without depression) troubled by persistent problems bupropion and olanzapine , gel , and the PDE- 104,105 can benefit from treatment with either the tricyclic antidepres- 5 inhibitors sildenafil (both in male and female patients ) 106 sant or SSRIs87. The short-acting SSRI dapoxe- and tadalafil . Comparative studies are rare, but a placebo- tine is efficacious in treating , with controlled study found no evidence of efficacy for augmenta- either daily dosing or “on demand” dosage88. It has similar tion with mirtazapine or in female patients107. efficacy to paroxetine, though it may be less well tolerated89.A Augmentation of antidepressants with aripiprazole can im- systematic review of randomized placebo-controlled trials prove sexual interest and satisfaction in depressed women, with trazodone (which has partial agonist effects at 5-HT1A independent of an improvement in depressive symptoms108. receptors and antagonist effects at 5-HT2A and alpha-1 adren- Switching from one antidepressant drug to another seems rea- ergic receptors) indicates that it can be efficacious in reducing sonable and is commonly adopted103, but placebo-controlled

6 World Psychiatry 17:1 - February 2018 evidence of efficacy rests on a single study of switching from mon. Overall, sexual dissatisfaction is often associated with to (now withdrawn) nefazodone97. Switching from bipolar disorder52. one drug to another may lead to discontinuation symptoms, Patients with bipolar disorder tend to have more stable sex- and the replacement drug may prove less effective in control- ual partners and a more intense sexual activity than those with ling depressive symptoms. A single study found that regular ex- schizophrenia119,120. When compared to females, males with ercise prior to sexual activity improved sexual desire and global bipolar disorder tend to have more sexual partners and are sexual functioning in depressed women taking antidepres- more likely to have with strangers121. Sexual sants109. dysfunction is a common residual symptom in euthymic pa- Nitric oxide is involved in the of the male and tients with bipolar disorder, and has a significant negative female sexual response. In men, nitric oxide in the corpus cav- impact on quality of life, similar to that of residual depressive ernosum of the penis binds to guanylate cyclase receptors, symptoms and occupational stigma122. Moreover, impairment which results in increased levels of cyclic guanosine mono- in desire, excitement and ability to achieve orgasm is signifi- phosphate (cGMP), leading to smooth muscle relaxation (va- cantly associated with suicide plans or a feeling that life is not sodilation) in the intimal cushions of the helicine arteries, worth living123. In addition, sexual dysfunction has been iden- which in turn leads to vasodilation, increased blood flow into tified as a predictor of poor medication adherence124. the spongy tissue of the penis, and subsequent erection. Sil- A meta-analysis indicated a statistically significant associa- denafil, tadalafil and vardenafil are potent and selective inhibi- tion between a history of and a lifetime diagnosis tors of cGMP-specific PDE-5, which is responsible for deg- of , depression, eating disorders, sleep disor- radation of cGMP in the corpus cavernosum, resulting in more ders and suicide attempts125. Unfortunately, no longitudinal cGMP and facilitation of erection110. In women, the role of studies assessing patients with bipolar disorder are available nitric oxide and its interplay with is less well under- in this respect. Sexual aggression is common in youth with bi- stood, but the PDE-5 inhibitor enhancement of nitric oxide- polar disorder, particularly in those with a lifetime history of cGMP in non-adrenergic-non-cholinergic signalling for women comorbid post-traumatic disorder126. Prompt identifi- seems similar to the effect in men, and nitric oxide release cation and treatment of these youth is highly needed. results in vasodilatation in clitoral and vaginal tissues111. Routine enquiries about sexual life, including questions A series of randomized placebo-controlled trials demon- about sexual drive during manic episodes, accompanied by sim- strate that PDE-5 inhibitors are efficacious in resolving sexual ple psychoeducation, is highly recommended in bipolar patients dysfunction associated with antidepressants104-106. Studies of to mitigate the physical, psychic and family consequences of men with erectile dysfunction and depressive symptoms (but promiscuous and risky sexual behaviour. not undergoing antidepressant treatment) also show that pre- scription of PDE-5 inhibitors is often accompanied by a reduc- Influence of treatment of bipolar disorder on sexuality tion in depressive symptoms, enhanced quality of life, and im- proved interpersonal relationships112-114. Furthermore, preclin- Pharmacological management in bipolar disorder involves ical studies suggest that nitric oxide activity is an important the use of lithium, anticonvulsants, antipsychotics, antidepres- vulnerability factor in the Flinders rat depressive phenotype115, sants and benzodiazepines, either in monotherapy or in com- that passage of PDE-5 inhibitors across the blood-brain bar- bination. Sexual dysfunction is one of the most common side ef- rier can occur116, and that sildenafil has antidepressant-like fects of these medications, has a high impact on quality of life, effects after central muscarinic receptor blockade117. PDE-5 and is rated by patients as one of the most disabling problems. inhibitors are often helpful when managing patients with sex- Lithium is regarded as the first-line treatment in bipolar dis- ual dysfunction associated with antidepressants, but side ef- order, but several studies suggest some negative impact of this fects such as headache, dyspepsia and visual disturbances, and drug on sexual function, as it may reduce sexual desire, worsen the need for cautious use in patients with cardiovascular dis- erectile function and decrease sexual satisfaction127,128. Ap- ease, are all potential limitations. proximately one-third of patients receiving lithium experience sexual dysfunction, which usually involves more than a single domain, in both male and female patients119. Patients are sig- BIPOLAR DISORDER AND SEXUAL DYSFUNCTION nificantly less likely to experience sexual intercourse, sexual fantasies, sexual desire, pleasure and satisfaction, and 30% of Influence of bipolar disorder on sexuality them attribute these problems to lithium treatment129. Despite this, it seems that lithium has a less pronounced adverse im- Bipolar disorder can involve sexual disturbances directly pact on sexual function compared to other treatments in bipo- related to the illness phase. Male and female patients in manic lar disorder130, especially antipsychotics131. The combination or hypomanic episodes often experience , with of benzodiazepines with lithium seems to be associated with an increased incidence of risky sexual behaviours118. By con- an increased risk of sexual dysfunction, while this dysfunction trast, in depressive episodes, reduction of sexual desire is com- does not appear to be related to serum lithium levels132.

World Psychiatry 17:1 - February 2018 7 Anticonvulsants are often associated with sexual dysfunc- are needed to assess potential sexual dysfunction, and to man- tion in people with epilepsy (35-55% of patients)133, but there age it with the aims of preserving quality of life, maintaining is limited evidence of these adverse effects in patients with emotional experiences and continuing partner relationships. bipolar disorder134-136. Treatments with fewer adverse sexual effects should be con- Valproate may induce an increase of serum testosterone, an- sidered as potential first-line options in patients with severe drostenedione and dehydroepiandrosterone sulfate (DHEAS) mental illness interested in maintaining a sexual life. Manag- concentrations, while prolactin levels typically remain within ing treatment-emergent side effects adequately is crucial to normal limits137. 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