Flibanserin May Slightly Improve Sexual Function in Women, But Adverse Events May Limit Use

EBM Focus - Volume 11, Issue 16

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Reference - JAMA Intern Med 2016 Apr 1;176(4):453 (level 2 [mid-level] evidence)

  • Flibanserin was approved by the FDA in August of 2015 for the treatment of hypoactive sexual desire disorder in premenopausal women after being previously rejected twice for an unfavorable risk-benefit profile.
  • In a systematic review of 8 trials comparing flibanserin vs. placebo in women with hypoactive sexual desire disorder, flibanserin was associated with small improvements in the number of satisfying sexual encounters per months and sexual desire scores.
  • Flibanserin was also associated with a significant increase in mild-to-moderate adverse events including dizziness, somnolence, nausea, and fatigue; however, severe adverse events such as hypotension and syncope were not included in this analysis.

Sexual dysfunction is common in women, with approximately 40% of women in the United States reporting problems with desire, arousal, or orgasm and 20% reporting sexually-related personal distress (Obstet Gynecol 2008 Nov;112(5):970). Hypoactive sexual desire disorder is the most common type of female sexual dysfunction. Although it affects women of all ages, it is most prevalent in women aged 40-60 years and in those with surgically induced menopause (Obstet Gynecol 2011 Apr;117(4):996). In a controversial and highly publicized decision, the FDA approved flibanserin for the treatment of hypoactive sexual desire disorder in premenopausal women in August of 2015 after previously rejecting the drug twice for an unfavorable risk-benefit profile (FDA Press Release 2015 Aug 18, JAMA 2015 Sep 1;314(9):869). A recent systematic review was performed to determine the benefits and harms of flibanserin.

Eight trials (including 3 unpublished trials) comparing flibanserin vs. placebo in women with generalized hypoactive sexual desire disorder were included in this review. Six trials included premenopausal women and 2 trials included postmenopausal women. While at least 7,914 women were randomized (one trial did not report the number randomized), only 5,914 women completed the trials. Five trials assessed multiple does of flibanserin, but the most common dose was 100 mg given as either a single dose at bedtime or 50 mg twice daily. Only this dose was included in the meta-analysis. In the efficacy analysis, flibanserin was associated with a small, but statistically significant, improvement in the number of satisfying sexual encounters per months (weighted mean difference [WMD] 0.52, 95% CI 0.29-0.75). Statistically significant improvements were also found for the eDiary sexual desire score and the Female Sexual Function Index desire score, but these improvements were not clinically meaningful. Additionally, 2 trials included in this review asked women if they experienced a meaningful benefit from the trial medication and found a significant increase in the rate of positive response with flibanserin (NNT of 6-13) (J Sex Med 2012 Mar;9(3):793, J Sex Med 2012 Apr;9(4):1074). However, this data was not included in the meta-analysis. In the safety analysis, flibanserin was associated with an increased risk of side effects. The 4 adverse events with the greatest increase in risk were dizziness (risk ratio [RR] 4, 95% CI 2.56-6.27), somnolence (RR 3.97, 95% CI 3.01-5.24), nausea (RR 2.35, 95% CI 1.81-3.04), and fatigue (RR 1.64, 95% CI 1.27-2.13).

For women with hypoactive sexual desire disorder, there are few treatment options and most medications are associated with small improvements in sexual function and a high risk of adverse events. These results suggest that flibanserin is no different. In the FDA press release announcing the approval of flibanserin for premenopausal women, the described benefit was small and consistent with the findings of this systematic review (FDA Press Release 2015 Aug 18). The FDA press release also highlighted the potential adverse effects of flibanserin, including potentially serious hypotension and syncope if alcohol is used while taking flibanserin. While severe adverse events were only reported in 2 trials and were not included in this systematic review, the FDA required further studies to better understand these risks. This review did find an increase in a number of mild-to-moderate adverse effects and an increased rate of discontinuation due to adverse events with flibanserin, which may account for the high dropout rates in all 8 included trials. Overall, the results of this review suggest that while flibanserin is an option for women with hypoactive sexual desire disorder, most women are unlikely to find a clinically important improvement with this medication.

For more information, see the Female sexual dysfunction topic in DynaMed Plus. DynaMed users click here.


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