Flibanserin (Addyi), dubbed the “female Viagra”, offers “marginal” benefits to women who suffer from hypoactive sexual desire disorder (HSDD), according to new research
A team of researchers from Holland found that women taking the drug recorded an average of 0.5 additional satisfying sexual experiences (SSE) each month. But it also increased their risk of side effects, such as dizziness, sleeplessness, nausea and fatigue.
“The findings of this review suggest that the benefits of flibanserin treatment are marginal, particularly when taking into account the concurrent occurrence of adverse events,” the team says.
The researchers, who published their findings in JAMA International (online, 29 February 2016), based the results on a review of eight randomised clinical trials looking at the treatment effects of flibanserin, involving 5,914 premenopausal and postmenopausal woman. The drug was approved for use in premenopausal in the United States by the Food and Drug Administration (FDA) in August 2015 after being rejected twice before.
The FDA approval was underpinned by a “risk evaluation and mitigation strategy”, which means that the drug must be prescribed and dispensed by certified doctors and pharmacists, who will have undergone specific training. The FDA also added a ‘black box warning’ to the drug’s label highlighting the risk of severe low blood pressure and loss of consciousness when it is used with alcohol. The drug is not yet approved in Europe.
The researchers found that the pooled mean difference for SSE change from baseline was 0.49 (95% confidence interval [CI] 0.32–0.67) between 100mg flibanserin and placebo.
There was a two-fold increase in the risk of study discontinuation due to adverse events for women taking flibanserin compared with placebo (risk ratio 2.19, 95% CI 1.50-3.20). The risk ratio for dizziness was 4.00 (95% CI 2.56–6.27) in flibanserin versus placebo; 3.97 (95% CI 3.01–5.24) for sleeplessness; 2.35 (95% CI 1.85–2.98) for nausea; and 1.64 (95% CI 1.27–2.13) for fatigue.
The researchers say that the most common reported adverse events were of mild and moderate intensity, and that reports of serious adverse events were equally low in flibanserin and placebo users. “This reflects positively on flibanserin’s safety, but the conclusion that flibanserin is safe is premature,” they say.
The researchers acknowledge that their findings must be interpreted with caution because their review was based on studies that “were light on detail”, which affects the accuracy and quality of the evaluation.
“With nearly 90% of American physicians indicating that they would prescribe an approved HSDD pharmacological product over available non-pharmacological treatments, the need for sound evidence on the efficacy and safety profile of flibanserin is evident,” the research team adds.
The researchers call for further research before flibanserin can be recommended in guidelines and clinical practice. “Future studies should include women from diverse populations, particularly women with a history of somatic and psychological comorbidities, medication use, and surgical menopause.”
The authors of an accompanying editorial argue that the FDA approved a “marginally effective drug… in the face of substantial — and unnecessary — uncertainty about its dangers”.
“Women with distressing sexual desire problems need good treatments. We all need a drug approval process that delivers good decisions based on adequate evidence,” they conclude.
Tage Ramakrishna, chief medical officer and president of research and development at Valeant Pharmaceuticals, which manufactures Addyi, says the data used could not give reliable results. “[This] meta-analysis… provided little additional context. Meta-analyses using pooled data carry less statistical weight than the prospective, randomised, placebo-controlled trials used to secure FDA approval,” he says.
“It is crucial that women suffering from HSDD are able to speak to their physicians about the full range of options – including medical treatment – to manage this serious and well-established condition. Analyses such as the one published in JAMA Internal Medicine, by omitting context and downplaying the importance of increased sexually satisfying events to those with HSDD, makes that conversation more difficult.”
Natika Halil, chief executive of the sexual health charity FPA, says: “On the strength of the evidence presented in this study, it would appear there are very limited benefits, and more research is needed around sexual dysfunction in women to establish root causes and what effective treatments may be.”
 Jaspers L, Feys F, Bramer W M et al. Efficacy and safety of flibanserin for the treatment of hypoactive sexual desire disorder in women: a systematic review and meta-analysis. JAMA Intern Med 2016. doi: 10.1001/jamainternmed.2015.8565