Is 100mg Flibanserin Effective in Increasing the Number of Sexually Satisfying Events (SSE) in Women with Hypoactive Sexual Desire Disorder (HSDD)?

OBJECTIVE: The objective of this selective EBM review is to determine whether or not 100mg Flibanserin is effective in increasing the number of sexually satisfying events in women with HSDD. STUDY DESIGN: Review of three, placebo-controlled trials in which women \u3e 18 years old with HSDD were treated with either 100mg Flibanserin or a Placebo once daily qhs for 24 weeks DATA SOURCES: Three randomized, placebo-controlled trials found via PubMed searches and published in English peer-reviewed journals between 2011-2014 OUTCOMES MEASURED: Outcomes measured were the number of SSE over 4 weeks and analyzed with Wilcoxon’s rank-sum test. RESULTS: In DeRogatis et al, 100mg Flibanserin led to increases in the mean (standard error) SSE 1.6 (0.23) vs 0.80 (0.20) and was proven to be statistically significant (p CONCLUSIONS: Based on this review, 100mg Flibanserin taken once daily qhs is effective and well tolerated in treating those with HSDD in both pre- and postmenopausal women. The mean number of SSE was statistically significant vs. placebo in all three studies

Effect of Flibanserin Treatment on Body Weight in Premenopausal and Postmenopausal Women with Hypoactive Sexual Desire Disorder: A Post Hoc Analysis.

Background: Flibanserin, a 5-HT1A agonist and 5-HT2A antagonist, is indicated for the treatment of acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women. This post hoc analysis evaluated the effect of flibanserin treatment on body weight in premenopausal and postmenopausal women with HSDD. Materials and Methods: This analysis included three 24-week, double-blind, placebo-controlled studies of flibanserin 100 mg each bedtime (qhs) in premenopausal women, a similarly designed study in postmenopausal women, and a 52-week, open-label extension study in premenopausal women. Results: In a pooled analysis of premenopausal women, mean baseline body mass index (BMI) was 27.0 kg/m2 in the flibanserin group (n = 1227) and 26.8 kg/m2 in the placebo group (n = 1238). Among patients who completed 24 weeks of treatment, least squares (LS) mean weight change was −1.4 kg in the flibanserin group (n = 1010) and −0.1 kg in the placebo group (n = 1066; p \u3c 0.0001). Weight loss ≥5% from baseline was reported in 21.0% of patients who received flibanserin and 7.8% of patients who received placebo; weight loss ≥10% was reported in 3.8% and 2.0% of patients, respectively. In postmenopausal women, mean baseline BMI was 27.7 kg/m2 in the flibanserin group (n = 467) and 27.3 kg/m2 in the placebo group (n = 480). LS mean weight change at week 24 was −1.8 kg in the flibanserin group (n = 385) and −0.1 kg in the placebo group (n = 425; p \u3c 0.0001), with weight loss ≥5% reported in 24.7% and 7.3% of patients, respectively, and weight loss ≥10% reported in 5.2% and 1.7%, respectively. In HSDD patients with \u3e12 months (n = 880) and \u3e18 months (n = 637) of exposure to flibanserin, mean weight change was −1.0 and −1.2 kg, respectively; 25.4% and 26.9% of patients, respectively, experienced weight loss ≥5% from baseline, and 7.8% and 8.4%, respectively, experienced weight loss ≥10%. Conclusions: Women treated with flibanserin for HSDD may experience weight loss

Flibanserin: a serendipitous story

Female sexual disorders are increasingly being recognized in the population and hypoactive sexual desire disorder (HSDD) is one of the commonest sexual disorders among females. The prevalence of the disease varies between 10-20% in the Caucasian population. Testosterone is the only treatment that is approved by the European Medical Agency. Flibanserin is a drug that has been approved by the US FDA for HSDD among pre-menopausal women in 2015. Flibanserin is a 5-HT1A receptor agonist and 5-HT2A receptor antagonist that rebalances the neural circuitry involved in processing sexual desire by reducing serotonin activity and enhancing dopamine and epinephrine activity. The efficacy of the drug was confirmed in three pivotal randomized placebo control trials in premenopausal women who consumed the drug for 24 weeks. There was a significant improvement in the number of sexually satisfying events. The most common safety concerns for flibanserin as seen in clinical trials were somnolence, hypotension and syncope. The drug is prescribed at a dose of 100 mg once daily at bed time. The marginal efficacy of the drug coupled with other safety concerns, such as hypo-tensions have given room for much criticism over the drug’s approval by the FDA. Nevertheless, on a positive note the serendipitous discovery of flibanserin and its repurposing for HSDD is a compelling narrative in its drug development history. It remains to be seen if the long term safety of the molecule and the efficacy of the molecule in non-trial settings could make it an attractive pharmaco-therapeutic option for HSDD

Region-dependent effects of flibanserin and buspirone on adenylyl cyclase activity in the human brain

The mode of action of antidepressant drugs may be related to mechanisms of receptor adaptation, involving overall the serotonin 1A (5-HT1A) receptor subtype. However, so far, the clinical effectiveness of selective compounds acting at this level has proved disappointing. This could be explained by the heterogeneity of 5-HT1A receptors within the central nervous system. In animals, two 5-HT1A agonists, flibanserin and buspirone, have shown different pharmacological properties, depending on the brain region. Since no evidence supports this observation in humans, this study sought to investigate whether these two drugs exert different effects on 5-HT1A receptor activation in three different human brain areas: the prefrontal cortex, hippocampus and raphe nuclei. 5-HT1A-mediated inhibition of forskolin-stimulated adenylyl cyclase (AC) was taken as an index of 5-HT1A receptor activation. Flibanserin significantly reduced the activity of AC post-synaptically, i.e. in the prefrontal cortex [EC50 (mean +/- S.E.M.), 28 +/- 10.2 nM; Emax, 18 +/- 2.3%] and in the hippocampus (EC50, 3.5 +/- 3.1 nM; Emax, 20 +/- 4.0%), but had no effect in the raphe nuclei, i.e. at pre-synaptic level. Vice versa, buspirone was only slightly but significantly effective in the raphe (EC50, 3.0 +/- 2.8 nM; Emax, 12 +/- 1.9%). Agonist effects were sensitive to the 5-HT1A antagonists WAY-100135 and pindobind 5-HT1A in the cortex and raphe nuclei, whereas buspirone antagonized flibanserin in the hippocampus. These findings suggest a region-related action of flibanserin and buspirone on forskolin-stimulated AC activity in human brain

Retinal Neuroprotective Effects of Flibanserin, an FDA-Approved Dual Serotonin Receptor Agonist-Antagonist

Purpose: To assess the neuroprotective effects of flibanserin (formerly BIMT-17), a dual 5-HT1A agonist and 5-HT2A antagonist, in a light-induced retinopathy model. Methods: Albino BALB/c mice were injected intraperitoneally with either vehicle or increasing doses of flibanserin ranging from 0.75 to 15 mg/kg flibanserin. To assess 5-HT1A-mediated effects, BALB/c mice were injected with 10 mg/kg WAY 100635, a 5-HT1A antagonist, prior to 6 mg/kg flibanserin and 5-HT1A knockout mice were injected with 6 mg/kg flibanserin. Injections were administered once immediately prior to light exposure or over the course of five days. Light exposure lasted for one hour at an intensity of 10,000 lux. Retinal structure was assessed using spectral domain optical coherence tomography and retinal function was assessed using electroretinography. To investigate the mechanisms of flibanserin-mediated neuroprotection, gene expression, measured by RT-qPCR, was assessed following five days of daily 15 mg/kg flibanserin injections. Results: A five-day treatment regimen of 3 to 15 mg/kg of flibanserin significantly preserved outer retinal structure and function in a dose-dependent manner. Additionally, a single-day treatment regimen of 6 to 15 mg/kg of flibanserin still provided significant protection. The action of flibanserin was hindered by the 5-HT1A antagonist, WAY 100635, and was not effective in 5-HT1A knockout mice. Creb, c-Jun, c-Fos, Bcl-2, Cast1, Nqo1, Sod1, and Cat were significantly increased in flibanserin-injected mice versus vehicle-injected mice. Conclusions: Intraperitoneal delivery of flibanserin in a light-induced retinopathy mouse model provides retinal neuroprotection. Mechanistic data suggests that this effect is mediated through 5-HT1A receptors and that flibanserin augments the expression of genes capable of reducing mitochondrial dysfunction and oxidative stress. Since flibanserin is already FDA-approved for other indications, the potential to repurpose this drug for treating retinal degenerations merits further investigation

Is Flibanserin a Safe and Effective Treatment to Increase Sexual Desire in Premenopausal Women with Hypoactive Sexual Desire Disorder?

OBJECTIVE: The objective of this selective EBM review is to determine whether or not Flibanserin is a safe and effective treatment to increase sexual desire in premenopausal women with Hypoactive Sexual Desire Disorder. STUDY DESIGN: Review of three randomized controlled trials published in 2013, 2012, and 2012; selection was based on their relevance to the clinical question and if they contained patient oriented outcomes. DATA SOURCES: Three peer-reviewed randomized controlled trials comparing the use of Flibanserin to placebo in the treatment of Hypoactive Sexual Desire Disorder were found on PubMed. OUTCOME(S) MEASURED: For each trial patients were divided into two groups and assigned to either Flibanserin treatment or placebo treatment. Each trial assessed number of satisfying sexual events (SSE), Patient Global Impression of Improvement (PGI-I), and Adverse Events (AEs), events leading to the discontinuation of the trial. RESULTS: All three trials showed a statistically significant (p CONCLUSIONS: Based on all three trials, there is a statistically significant increase in sexual desire with the use of Flibanserin compared to the use of placebo in premenopausal women with HSDD. The analysis of PGI-I showed a moderately low NNT indicating that the drug, Flibanserin, was effective in improving the women’s condition. The analysis of AEs showed a moderate numbers needed to harm indicating that there are risks to taking Flibanserin. All serious safety concerns were investigated and deemed not related to the use of Flibanserin. Flibanserin is a relatively safe drug, and is an effective treatment of HSDD symptoms in premenopausal women

Sexually “Broken”: The Rhetorical Production of The Distressed Nonsexual in The Flibanserin Debate & Beyond

Using a Foucauldian-influenced approach to discourse and power, this thesis analyzes the production of nonsexualities, such as the lack of sexual desire, in the contemporary United States. In psychiatric discourse, the distressed nonsexual subject is produced as the patient with Hypoactive Sexual Desire Disorder (HSDD). This discursive formation was put to use in the debate surrounding pharmaceutical drug flibanserin (Addyi) in order to secure its approval by the FDA in 2015. I posit that, by emphasizing the distress of the HSDD patient experience, the rhetoric of pro-flibanserin advocacy succeeded in producing an ethical exigency, arguing that it would be cruel for the FDA to reject the drug. Centrally, its support for this claim relies upon the construction of an ideal (hetero)sexual marriage and problematizing nonsexuality as a threat to love. Flibanserin’s rhetorical support depended, then, upon casting nonsexuality in the role of a destructive enemy force. As a counter-discourse, the discourse of the asexual community—which produces “asexuality” as a sexual orientation—codifies a point of resistance to these claims

Flibanserin and 8‐OH‐DPAT Implicate Serotonin in Association between Female Marmoset Monkey Sexual Behavior and Changes in Pair‐Bond Quality

Introduction.  Psychopathological origins of personally distressing, hypoactive sexual desire disorder (HSDD) in women are unknown, but are generally attributed to an inhibitory neural regulator, serotonin (5‐HT). Flibanserin, a 5‐HT 1A agonist and 5‐HT 2A antagonist, shows promise as a treatment for HSDD. Aim.  To test the hypothesis that female marmoset sexual behavior is enhanced by flibanserin and diminished by 8‐OH‐DPAT, in order to evaluate the efficacy of serotonergic modulation of female sexual behavior in a pairmate social setting comparable to humans. Methods.  Sexual and social behavior were examined in eight female marmoset monkeys receiving daily flibanserin (15 mg/kg), 8‐OH‐DPAT (0.1 mg/kg), or corresponding vehicle for 15–16 weeks in a counterbalanced, within‐subject design, while housed in long‐term, stable male–female pairs. Main Outcome Measures.  Marmoset pairmate interactions, including sexual and social behavior, were scored during weeks 5–6 of daily flibanserin, 8‐OH‐DPAT or vehicle treatment. 24‐hour pharmacokinetic profiles of the drugs and their metabolites, as well as drug‐induced acute symptoms of the 5‐HT behavioral syndrome were also assessed. Results.  Two‐way analysis of variance reveals that flibanserin‐treated females attract more male sexual interest ( P  = 0.020) and trigger increased grooming ( P  = 0.001) between partners. In contrast, 8‐OH‐DPAT‐treated females show increased rejection of male sexual advances ( P  = 0.024), a tendency for decreased male sexual interest ( P  = 0.080), and increased aggression with their male pairmates ( P  = 0.049). Conclusions.  While 8‐OH‐DPAT‐treated female marmosets display decreased sexual receptivity and increased aggressive interactions with their male pairmates, flibanserin‐treated female marmosets demonstrate increased affiliative behavior with their male pairmates. Such pro‐affiliation attributes may underlie flibanserin's effectiveness in treating HSDD in women. Aubert Y, Gustison ML, Gardner LA, Bohl MA, Lange JR, Allers KA, Sommer B, Datson NA, and Abbott DH. Flibanserin and 8‐OH‐DPAT implicate serotonin in association between female marmoset monkey sexual behavior and changes in pair‐bond quality. J Sex Med 2012;9:694–707.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90344/1/j.1743-6109.2011.02616.x.pd