How effective and safe is flibanserin (Addyi; Valeant) for the treatment of hypoactive sexual desire disorder (HSDD) in women?  A new study published in JAMA Internal Medicine aimed to assess the clinical benefits of this new prescription drug which has stirred up controversy since even before its FDA approval back in August 2015. This is the first systematic review and meta-analysis to address the clinical impact of flibanserin in treating women with HSDD.

While the mechanism of action for flibanserin in the treatment of HSDD is unknown, it is thought to work by restoring prefrontal cortex control over the brain’s motivation/rewards structures enabling sexual desire to manifest. Specifically, flibanserin increases dopamine and norepinephrine while transiently decreasing serotonin in the brain’s prefrontal cortex, which may be accomplished by reduced glutamate transmission. In vitro, flibanserin has demonstrated high agonist activity at 5-HT1A receptors and antagonist activity at 5-HT2A receptors; it also has moderate antagonist activities at the 5-HT2B, 5-HT2C, and dopamine D4 receptors.

For this study, researchers included eight studies (five published, three unpublished) which included nearly 6000 women (both pre- and postmenopausal) with generalized acquired HSDD according to the Diagnostic and Statistical Manual of Mental Disorders (4th Edition, Text Revision); all studies were randomized, double-blind, placebo-controlled trials. Primary efficacy outcomes included the number of satisfying sexual events (SSEs), monthly sexual desire intensity (eDiary desire score), and Female Sexual Function Index desire domain (FSFI desire). In addition to these, five secondary efficacy outcomes (FSFI total score, Female Sexual Distress Scale-Revised Item 13 and total score, Patient’s Global Impression of Improvement, Patient Benefit Evaluation) and safety outcomes (any adverse events, investigator-defined drug-related adverse events, adverse events leading to study discontinuation, severe/serious adverse events) were included in the analysis.

Results indicate that the impact of flibanserin in producing a meaningful change in women with HSDD was small; patient’s global impression of improvement scores showed minimal improvement to no change. When comparing flibanserin 100mg to placebo, researchers found that the pooled mean difference in SSE change from baseline was 0.49 (95% CI, 0.32–0.67); this varied depending on whether the study was published (0.58 [95% CI, 0.37-0.80]) or unpublished  (0.31 [95% CI, 0.00-0.62]) and also when factoring in premenopausal women only (0.65 [95% CI, 0.38-0.92]). For eDiary desire score, which was only measured in premenopausal women, the mean difference in change from baseline was 1.63 (95% CI, 0.45–2.82); for FSFI desire it was 0.27 (95% CI, 0.17–0.38). A statistically significant difference was seen between flibanserin 100mg versus placebo in all primary and secondary outcomes.