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| 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.
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| 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 from the Erasmus
University Medical
Center, Rotterdam,
the Netherlands,
Included 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and 3 unpublished studies constituting a total of 5914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.
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