Flibanserin: initial evidence of efficacy on sexual dysfunction, in patients with major depressive disorder.

Flibanserin, a novel 5-HT(1A) agonist and 5-HT(2A) antagonist, has the potential to treat sexual dysfunction. Provide historical perspective on the rationale for development of flibanserin to treat sexual dysfunction, based on post hoc analyses of data. The Arizona Sexual Experiences (ASEX) scale and the Hamilton depression rating scale (HAMD) Genital Symptoms item. Sexual function outcomes are presented from four double-blind, randomized controlled studies involving a total of 369 men and 523 women diagnosed with Major Depressive Disorder. Each study had an active treatment arm to confirm assay sensitivity on the primary antidepressive endpoint. Two studies placebo, flibanserin (50mg bid), or fluoxetine (20mg qd) for 6 weeks and two involved placebo, flibanserin (50-100mg bid), or paroxetine (20-40mg qd) for 8 weeks. Individual study completion rates were 77-80%. At baseline, 38% of men and 67% of women reported sexual dysfunction. Assay sensitivity was not demonstrated in the fluoxetine trials and sexual function outcomes were inconsistent. Flibanserin and placebo were associated with low rates of treatment-emergent sexual dysfunction in women during the paroxetine studies. In one study, 70% of flibanserin-treated women with baseline sexual dysfunction reported improvement in sexual function, compared with 30% of placebo-treated women. Mean change from baseline on the HAMD "Genital Symptoms" item in one paroxetine study was significantly better among flibanserin- than placebo-treated women at weeks 4, 6, and 8 (P<0.05). Sexual function adverse events across flibanserin groups were generally comparable to placebo. Although these studies were not designed or powered to compare sexual function outcomes, results suggested a potential benefit of flibanserin on sexual function, particularly on female sexual desire, and provided a rationale to evaluate the efficacy of flibanserin as a treatment for female hypoactive sexual desire disorder.