Flibanserin: Initial Evidence of Efficacy on Sexual Dysfunction, in Patients with Major Depressive Disorder

Abstract

Introduction Flibanserin, a novel 5-HT1A agonist and 5-HT2A antagonist, has the potential to treat sexual dysfunction. Aim Provide historical perspective on the rationale for development of flibanserin to treat sexual dysfunction, based on post hoc analyses of data. Main Outcome Measures The Arizona Sexual Experiences (ASEX) scale and the Hamilton depression rating scale (HAMD) Genital Symptoms item. Methods 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 (50 mg bid), or fluoxetine (20 mg qd) for 6 weeks and two involved placebo, flibanserin (50–100 mg bid), or paroxetine (20–40 mg qd) for 8 weeks. Results 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. Conclusions 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.

Sexual dysfunction in diabetic women

“…Tibolone has androgenic, estrogenic, and progesterone activity and it has been shown to improve desire, arousal, and lubrication. 95,103,107 Phentolamine is an a-antagonist that improves arousal and lubrication; 108 apomorphine, 94 a-melanocyte-stimulating hormones, 109 serotonin receptor antagonists, 110 and selective estrogen and androgen receptor modulators are in phase II trials. 112 Vasodilators as L-arginin, 112 alprostadile, 113 and herbal therapy (gingko biloba) 112 have an as yet undetermined role in the treatment of FSD.…”

Preclinical Abuse Potential Assessment of Flibanserin: Effects on Intracranial Self-Stimulation in Female and Male Rats

“…Flibanserin is a serotonin receptor subtype 1A (5HT1A) agonist and 2A (5HT2A) antagonist [1, 2] that has shown efficacy in treating female sexual interest/arousal disorder, formerly known as hypoactive sexual desire disorder [3, 4]. Although precise mechanisms of flibanserin effects on sexual behavior are still under study, flibanserin has been shown in rats to alter extracellular levels of dopamine and serotonin in the prefrontal cortex and nucleus accumbens in both male [5] and female rats [6, 7].…”

Flibanserin: a serendipitous story

“…However the drug was found to improve the sexual health of the female participants in the study. 13 It was this initial observation that spurred on the impetus for developing the molecule in the treatment of hypoactive sexual desire disorder. The drug has also been studied in post-menopausal women and as shown improvement in sexual desire and it increase in the number of sexually satisfying events.…”