What is known of differences in occurrence of sexual side effects of different antipsychotics?

Fråga: What is known of differences in occurrence of sexual side effects of different antipsychotics? Can support be found as a basis for specific recommendations if side effects have occurred?

Sammanfattning: Limited support can be found in the literature for recommendations on switching between different antipsychotics when the patient experiences sexual dysfunction. Variations in frequency of sexual dysfunction have been seen between different drugs but available studies are small and have short follow up times. Patients who are treated with risperidone or classical antipsychotics might experience fewer problems with sexual dysfunction if treatment is substituted with olanzapine. If the patient experience erectile dysfunction sildenafil may have beneficial effect. Some limited support can be found for a change to or addition of aripiprazole for patients experiencing sexual dysfunction with other antipsychotics.

Svar: Fifty to sixty per cent of schizophrenic patients experience sexual dysfunction during treatment with antipsychotics. This corresponds to 31 % in the general male population. Antipsychotics can cause sexual dysfunction through a number of mechanisms such as sedation, hyperprolactinemia, and antagonist effect on alpha adrenergic-, dopamine-, histamine-, and muscarinic receptors. The psychotic disease in itself and other concomitant medication can cause sexual dysfunction in psychotic patients as well. Antipsychotic medication is the most common cause of hyperprolactinemia in patients with severe psychiatric disease. The degree of prolactin increase varies between different substances and some studies indicate that atypical antipsychotics cause less sexual dysfunction than risperidone and classical antipsychotics whereas other studies does not identify any difference between first and second generation antipsychotics (1).<br><br>In 2012 an updated Cochrane review of the literature concerning sexual dysfunction caused by antipsychotic therapy was published. Side effects are related to problems with erection, vaginal secretion, orgasm, libido, retrograde ejaculation, sexual arousal, and general satisfaction concerning sexuality. These types of side effects have been reported for several psychotropic drugs. Incidences vary between different drugs and countries however. Suggested strategies to handle the problems include stopping treatment for a shorter period drug holiday, dose reduction, change of antipsychotics, and symptomatic treatment. Two of the four studies included in the review described effects of sildenafil and selegiline compared to placebo for treatment of sexual dysfunction. The other two studies evaluated the effect of a change of the antipsychotic drug and continued treatment with unchanged antipsychotic drug. These two studies included both men and women. All studies were small and follow up times were less than four months. A meta-analysis could not be conducted since the investigated interventions differed in the studies (2).<br><br>The quality of the available evidence is very low according to the authors of the report. No studies were identified that investigated other strategies such as a shorter stop of treatment or dose reduction. In a cross-over study with two weeks follow up, patients (n=31) had significantly more erections adequate for penetration when sildenafil was used compared to placebo (average difference 3.2 and 95 % confidence interval (CI) 1.83-4.57). Differences were seen in average duration of erection (average difference 1.18 minutes and 95 % CI 0.52-1.84) and number of satisfactory intercourses (average difference 2.84 and 95% CI 1.61-4.07). The authors of the Cochrane analysis concludes that sildenafil may constitute a functioning treatment addition for men, the study was small though, and follow-up was conducted after only two weeks. Selegiline was not more effective than placebo after three weeks of treatment of sexual dysfunction caused by antipsychotic treatment in men in a small study (2).<br><br>A study (n=54) compared unchanged treatment with risperidon or classical antipsychotics to a switch to olanzapine, in men and women with sexual side effects during treatment. A statistically significant difference was seen in improvement of sexual dysfunction measured by the GISF scale (Global Impressions of Sexual Function) after four months (average difference -0.80 and 95% CI -1.55 to -0.05). Lower levels of prolactin were seen with the change to olanzapine (average difference -30.84 ng/ml and 95% CI -47.46 to -14.22). No improvement was seen in sexual function after six weeks when risperidon was changed to quetiapine. Prolactin levels were significantly lower in a subgroup of the patients who switched to quetiapine (2).<br><br>In a randomized open-label trial on sexual function 44 patients were switched from another antipsychotic drug to either aripiprazol or risperidone. 36 patients remained at the end of the study, 18 in each group. Among those patients 11 of the patients receiving risperidone and one of those receiving aripiprazole experienced sexual dysfunction (p=0,001). Prolactin levels were significantly higher among the risperidone patients (3). The small size of the study and lack of evaluation of baseline characteristics are important limitations.<br><br>In an open-label study effects on sexual dysfunction were studied in 27 patients with insufficient treatment effect, or who did not tolerate their antipsychotic treatment. Patients switched to aripiprazole alone or in combination with the antipsychotic drug they were on before the study (54%). 9 patients received risperidone, 9 olanzapine, 4 amisulpride, 3 quetiapine, 1 zuclopenthixol and 1 clozapine. Significant positive effects were seen at 12 weeks on prolactine, and in men on volume of ejaculate, free androgen index, and testosterone, and in women on estradiol. At week 26 significant effects were seen in libido and sexual function and in men on erectile dysfunction, volume of ejaculate, and free androgen index, and in women on menstrual dysfunction as well as estradiol (4).<br><br>A review from 2012 identifies a number of open-label studies describing a change of treatment to aripiprazole, ziprasidone, olanzapine, and quetiapine with an improvement in sexual function and/or prolactin levels. The number of patients in these studies was few though. Open-label studies were also identified where aripiprazole, vardenafil, cabergoline, amantadine, or imipramine were used as additional treatment in patients with sexual dysfunction induced by antipsychotics. Improvements in sexual function and/or hormonal profile were seen. However, the studies were small (n<30) and time to follow-up short (<3 months) (1).<br><br>A meta-analysis from 2011 quantified differences in sexual dysfunction in patients treated with different antipsychotics. Quetiapine, ziprasidone, perfenazin, and aripiprazole were associated with a relatively low frequency of sexual dysfunction (16-27%) whereas olanzapine, risperidone, haloperidol, clozapine, and thioridazine were associated with higher frequencies (40-60%). The authors point out that data for aripiprazole, clozapine, perfenazin, and thioridazine were not replicated consistently and should be interpreted with caution. Also, the choice of method for measuring sexual dysfunction in the different studies was seen to have significant effects on the results for many of the studied drugs. Furthermore data from randomized controlled studies yield a lower frequency of sexual dysfunction for olanzapine, quetiapine, and risperidone when analyzed separately than in the analysis of the whole material, indicating that the true frequency might actually be lower for these drugs than what the whole material indicates (5).<div id="referenser" style="display:none;">Nunes LV, Moreira HC, Razzouk D, Nunes SO, Mari Jde J. Strategies for the treatment of antipsychotic-induced sexual dysfunction and/or hyperprolactinemia among patients of the schizophrenia spectrum: a review. J Sex Marital Ther 2012;38(3):281-301<br>Schmidt HM, Hagen M, Kriston L, Soares-Weiser K, Maayan N, Berner MM. Management of sexual dysfunction due to antipsychotic drug therapy. Cochrane Database Syst Rev 2012 Nov 14;11:CD003546<br>de Boer MK, Wiersma D, Bous J,Sytema S, van der Moolen AE, Wilffert B, Hamamura T, Knegtering H. A randomized open-label comparison of the impact of aripiprazole versus risperidone on sexual functioning (RAS study). J Clin Psychopharmacol 2011 Aug;31(4):523-5<br>Mir A, Shivakumar K, Williamson RJ, McAllister V, O´Keane V, Aitchison KJ. Change in sexual dysfunction with aripiprazole: a switching or add-on study. J Psychopharmacol 2008 May;22(3):244-53<br>Serretti A, Chiesa A. A meta-analysis of sexual dysfunction in psychiatric patients taking antipsychotics. Int Clin Psychopharmacol 2011 May;26(3):130-40</div>