The JAMA analysis misleadingly concluded that flibanserin increased SSEs by an average of only 0.49 per month, therefore concluding that its effects were weak and outweighed by adverse effects of dizziness and somnolence. Their meta-analysis included dosing studies using the ineffective lower doses of 25 mg and 50 mg, diluting the results.
Using the FDA-required tool of SSE for women is an issue and important for women’s health clinicians to understand when reviewing the clinical trials and the history of delayed approval of flibanserin.5
Using SSE is a carryover from the FDA’s approval process for PDE5 inhibitors (like sildenafil), which specified that a man with significant erectile dysfunction cannot have an SSE without an erection. Clearly, women can and do have sexual events whether interested or not. (Some women have referred to this as “duty sex.”) These events were reported to happen 2.5 times a month in the flibanserin trials. This raises the baseline creating a ceiling effect on SSEs (2.5 at baseline + placebo effect +flibanserin effect = about 6 times per month.)
Interestingly and importantly, women who responded to flibanserin had on average 2.5 to 4 additional SSEs per month when compared to placebo and one quarter of the responders had more than 4 additional SSEs per month.
Also when interpreting a mean increase of “one extra sexually satisfying event per month,” perspective is vital and a woman will be able to assess that herself. For the most part, the women enrolled in the trials were very healthy and in long-standing committed relationships with higher-than-average rates of SSEs at baseline.
At least 50% of women have a self-reported meaningful response to flibanserin and those who do not respond can stop therapy. Furthermore, the adverse effects of dizziness, hypotension, and somnolence can be reduced by taking the medicine at night and avoiding alcohol, which can raise flibanserin blood levels.
The JAMA editorial incorrectly stated that flibanserin carries a “black box warning.” Rather, it carries a boxed warning that using the drug with alcohol increases the risk of hypotension and syncope because it is processed through the cytochrome CYP3A4 pathway, as are antifungal medications taken for vaginal yeast infections.
In contrast to the alcohol challenge study, in the pivotal clinical trials on flibanserin, approximately 60% of women studied admitted to social alcohol use. Therefore, the FDA required a somewhat contrived additional alcohol challenge study that led to the development of a Risk Evaluation and Mitigation Strategy (REMS) program in order for certified physicians to prescribe and for certified pharmacists to dispense the drug.