A new review hype the controversy associated with the ‘pink pill’ commonly dubbed as ‘Female Viagra’.

 

Image Courtesy: L.A. Times

The little pink pill or Flibanserin (Addyi, Sprout Pharmaceuticals)  also dubbed  as the "Female Viagra" was approved by the US Food and Drug Administration (FDA) for the treatment of  hypoactive sexual desire disorder (HSDD) in premenopausal women,  in August 2015, despite  being unsure  about suboptimal risk-benefit trade-offs.

Image Courtesy:  Chicago Tribune

Flibanserin, a 5-HT1A agonist, a 5-HT2A antagonist, and a very weak partial agonist on dopamine D4 receptors, increases levels of dopamine and norepinephrine and decreases serotonin in animal brain areas. Therefore, since dopamine and norepinephrine are thought to promote and serotonin is thought to inhibit sexual desire and arousal, it was suggested that flibanserin enhances sexual desire in HSDD,

A recent systematic review and meta-analysis of randomized clinical trials was published on line on February, 2016 in Journal of American Medical Association (JAMA10.1001/jamainternmed.2015.8565) which assessed efficacy and safety of flibanserin for the treatment of HSDD in women.

The approval of Flibanserin by FDA (a failed antidepressant) has always been shrouded in mystery. It was rejected by FDA twice before it was approved by FDA in August 2015; its clinical review team which voted against it advocating that the benefit-harm balance was unfavorable was overruled by the Clinical Pharmacology and Clinical Division Director. He acknowledged ‘the limited efficacy and worrisome harms, but emphasized the unmet need in women for whom other treatments failed.’

In the recent review by Jaspers L et al from the Erasmus University Medical Center, Rotterdam, the Netherlands, Included five published and 3 unpublished studies constituting a total of   5914 women. The Primary efficacy outcomes were number of satisfying sexual events (SSEs), eDiary sexual desire, and Female Sexual Function Index (FSFI) desire. Safety outcomes were 4 common adverse events (AEs): dizziness, somnolence, nausea, and fatigue and many others. The inclusion of studies focusing on postmenopausal women took into account the potential off-label use.

The study found minimal benefit by the use of Addyi, specifically the pooled mean difference for a Sexually Satisfying Event (SSE) between 100 mg of Flibanserin and placebo was .49%, 1.63 for ediary desire and .27% for Female Sexual Function Index (FSFI) desire domain.

This means that the drug only added .5 additional satisfying sexual experiences per month, while the incidence of adverse effects increased four fold said the study coauthor Ellen T. M. Laan, PhD, from the Department of Sexology and Psychosomatic Obstetrics and Gynecology, Academic Medical Center, University of Amsterdam, the Netherlands, said in a recorded interview with JAMA Internal Medicine.

The risk ratio for study discontinuation due to adverse events was 2.19. The most bothersome was syncope and hypotension that occurred with concurrent alcohol use or CYP3A4 inhibitors, including oral contraceptives and fluconazole.

Meanwhile, many physicians have questioned the results of the study and have reported favorable results with many of the patients using it. They also believe that  the women should be allowed to make an informed decision to choose the ‘pink pill’ as the men are allowed to make an informed decision about ‘Viagra’.

On the basis of the study findings the authors concluded that “The findings of this review suggest that the benefits of flibanserin treatment are marginal, particularly when taking into account the concurrent occurrence of AEs.”

More robust evidence on its safety profile and efficacy is needed before a recommendation can be made in guidelines and clinical practice regarding its use, as majority of American physician indicated that they would prefer an approved HSDD pharmacological product over available non-pharmacological treatments. Further, it is known that an integrative approach involving psychological interventions play a crucial role in treatment of HSDD.

The authors acknowledge the limitation of the study and recommend that future studies should include women from more diverse ethnicity, with a history of somatic and psychological co-morbidities, medication use, and surgical menopause.

References:

http://www.jsm.jsexmed.org/article/S1743-6095%2815%2931530-7/abstract

http://link.springer.com/article/10.1007%2Fs10508-012-0062-0

http://www.cnn.com/2016/02/29/health/female-viagra-gets-mixed-reviews/index.html

http://archinte.jamanetwork.com/article.aspx?articleid=2497781#ioi150116r17

http://archinte.jamanetwork.com/article.aspx?articleid=2497781

http://www.jsm.jsexmed.org/article/S1743-6095%2815%2932579-0/pdf