Efficacy and Safety of Flibanserin for the Treatment of Hypoactive Sexual Desire Disorder in Women

Abstract

, the US Food and Drug Administration (FDA) approved flibanserin as a treatment for hypoactive sexual desire disorder (HSDD) in premenopausal women, despite concern about suboptimal risk-benefit trade-offs. OBJECTIVE To conduct a systematic review and meta-analysis of randomized clinical trials assessing efficacy and safety of flibanserin for the treatment of HSDD in women. DATA SOURCES Medical databases (among others, Embase, Medline, Psycinfo) and trial registries were searched from inception to June 17, 2015. Reference lists of retrieved studies were searched for additional publications. STUDY SELECTION Randomized clinical trials assessing treatment effects of flibanserin in premenopausal and postmenopausal women were eligible. No age, language, or date restrictions were applied. Abstract and full-text selection was done by 2 independent reviewers. DATA EXTRACTION AND SYNTHESIS Data were extracted by one reviewer and checked by a second reviewer. Results were pooled using 2 approaches depending on the blinding risk of bias. MAIN OUTCOMES AND MEASURES Primary efficacy outcomes included number of satisfying sexual events (SSEs), eDiary sexual desire, and Female Sexual Function Index (FSFI) desire. Safety outcomes included, among others, 4 common adverse events (AEs): dizziness, somnolence, nausea, and fatigue. RESULTS Five published and 3 unpublished studies including 5914 women were included. Pooled mean differences for SSE change from baseline were 0.49 (95% CI, 0.32-0.67) between 100-mg flibanserin and placebo, 1.63 (95% CI, 0.45-2.82) for eDiary desire, and 0.27 (95% CI, 0.17-0.38) for FSFI desire. The risk ratio for study discontinuation due to AEs was 2.19 (95% CI, 1.50-3.20). The risk ratio for dizziness was 4.00 (95% CI, 2.56-6.27) in flibanserin vs placebo, 3.97 (95% CI, 3.01-5.24) for somnolence, 2.35 (95% CI, 1.85-2.98) for nausea, and 1.64 (95% CI, 1.27-2.13) for fatigue. Women's mean global impression of improvement scores indicated minimal improvement to no change. CONCLUSIONS AND RELEVANCE Treatment with flibanserin, on average, resulted in one-half additional SSE per month while statistically and clinically significantly increasing the risk of dizziness, somnolence, nausea, and fatigue. Overall, the quality of the evidence was graded as very low. Before flibanserin can be recommended in guidelines and clinical practice, future studies should include women from diverse populations, particularly women with comorbidities, medication use, and surgical menopause.

Review Article: Sexuality and Risk-Reducing Salpingo-oophorectomy

“…Its use remains controversial because of limited symptom benefit and adverse effects. 74 Approximately 10% of women in the phase 3 trial reported significant improvement in sexual desire, 75 with a meta-analysis reporting flibanserin increased the rate of satisfying sexual events by only 0.5 per month. 74 This modest improvement, and the common adverse effects of dizziness, somnolence, nausea, and fatigue, should be discussed with women considering flibanserin.…”

Statistical and Epistemological Issues in the Evaluation of Treatment Efficacy of Pharmaceutical, Psychological, and Combination Treatments for Women's Sexual Desire Difficulties

“…Gao et al (2015) restricted their sample to four published RCTs and reported a standardized mean difference in SSEs of .59. Jaspers et al (2016) replicated this effect using the same sample of published studies with an additional published study in which only women who showed improvement in an open-label phase were retained and randomized to treatment or placebo (Goldfischer et al, 2011 (2016) and Clayton and Pyke (2016) suggested that future research could focus on direct comparisons between pharmaceutical and psychological treatments, or combination treatments for low desire in women. At this critical juncture of the clinical science on treatment of women's sexual difficulties, we welcome the opportunity to directly compare pharmaceutical and psychological treatments for low sexual desire.…”

“…The meta-analyses by Gao, Yang, Yu, and Cui (2015) and Jaspers et al (2016), examining efficacy and risks associated with flibanserin treatment, are excellent examples of variability in the strengths and weaknesses of meta-analysis, specifically -the file-drawer effect‖ to which Balon and Seagraves were referring. Gao et al (2015) restricted their sample to four published RCTs and reported a standardized mean difference in SSEs of .59.…”

Challenges in Designing Psychological Treatment Studies for Sexual Dysfunction

“…In this study, both treatment modalities produced similar levels of improvement in sex-related distress (Brotto, Seal, Third, a factor seldom considered in the context of treatment efficacy is how well women might tolerate the different treatments. Even if CBT or mindfulness are established as less effective than medications, these psychological approaches may be better tolerated given that they have not typically been associated with side effects such as those caused by some medications to treat low sexual desire in women (Jaspers et al, 2016). Because low sexual desire is not a fatal condition, it is likely that the risk-benefit ratio and the side-effect profile of a medication may be key in determining patient adherence.…”

“…The finding that flibanserin improves sexually satisfying events by only 0.5 -1 per month (Gao, Yang, Yu, & Cui, 2015;Jaspers et al, 2016) illustrates that the drug is not a panacea and that other treatment options are needed. Non-pharmacological treatments may be particularly appropriate for women who have significant psychological and/or dyadic contributors to their low desire, or simply cannot take flibanserin due to its serious interactions with alcohol and medications such as CYP3A4 inhibitors or other chronic medical conditions such as hepatic impairment.…”