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BOSTON -- Women with hypoactive sexual desire disorder (HSDD) attained broad and durable improvement in a variety of outcome measures when treated with flibanserin (Addyi), pooled data from three randomized trials showed.

As compared with placebo treatment, flibanserin led to significant improvement in standardized assessments of sexual desire, arousal, lubrication, orgasm, and satisfaction. Pain associated with sexual activity decreased significantly, and total score on the Female Sexual Function Index (FSFI) increased significantly in flibanserin-treated patients compared with placebo treatment.

The data extended the findings of the individual trials, which demonstrated improvement in the desire domain, Michael L. Krychman, MD, of the Southern California Center for Sexual Health and Survivorship Medicine in Newport Beach, Calif., said at the American Urological Association annual meeting.

"The effects are not exceptionally robust," said Krychman. "It has a restorative effect to normal in terms of desire. Women are not going to turn into these crazed sex fiends lurking around the corner for sexual activity. They may have more sexual thoughts. They may feel more sexy. They may be more responsive to their partners."

The urology community should welcome the availability of an effective treatment for HSDD, said Tomas Griebling, MD, of the University of Kansas Medical Center in Kansas City.

"Although we recognize that female sexual dysfunction is a significant problem, I think few urologists work with this in their clinical practices," said Griebling. "Part of the problem is frustration that we don't have much available to offer patients in the way of treatment. I see this drug, in many ways, as a ground-breaking development."

Almost 2 years ago flibanserin became the first FDA-approved treatment for generalized acquired HSDD. The approval, which required three attempts to pass muster with the FDA, occurred amid reservations about modest clinical activity and risks of adverse central nervous system (CNS) effects.

Less than a year after approval, controversy reared its head again, when published a review of eight clinical studies of flibanserin, plus an editorial, which collectively characterized supporting evidence as minimal, at best. Specialists in sexual medicine criticized the authors for inaccuracies and an "antimedication bias."

Flibanserin is a 5-HT_1A agonist/5-HT_2A antagonist that reduces serotonin activity and enhances dopamine and norepinephrine activity in specific regions of the cerebral cortex. Krychman reported findings from a pooled analysis of three separate placebo-controlled trials, involving a total of 2,368 patients randomized to flibanserin or placebo. The studies formed the basis for establishing the drug's safety and efficacy in premenopausal women with HSDD.

For the analysis, Krychman's group examined scores on the FSFI, which captures self-reported responses to questions or statements in six domains of sexual function: desire, arousal, lubrication, orgasm, satisfaction, and pain, as well as the total score. In the individual trials, the desire domain and total FSFI score were the primary outcomes, assessed after 24 weeks of randomized treatment.

The six domains of the FSFI comprise 19 items with score ranges of 1 to 5 for desire and 0 to 5 for the other domains, minimum score of 1.2 for desire and 0 for all others, and a maximum score of 6 for each domain. The possible total FSFI score ranges from 2 to 36.

The 2,368 patients had a mean age of about 36, and about 88% of the patients were white. The study population had a mean relationship duration of about 11 years and a mean HSDD duration of 4 to 5 years.

Weighted mean scores for each of the six domains showed significant improvement from baseline to 24 weeks in favor of flibanserin:

• Desire: 0.9 versus 0.4
• Arousal: 1.0 versus 0.6
• Lubrication: 0.9 versus 0.5
• Orgasm: 0.8 versus 0.5
• Satisfaction: 0.9 versus 0.6 (P<0.0001 for this and all comparisons above)
• Pain: 0.3 versus 0.1 (P<0.01)

The flibanserin group also had significantly greater improvement in total FSFI score from baseline (4.8 versus 2.9, P<0.0001).

Flibanserin was associated with significantly higher rates of adverse events, especially somnolence (12.8% versus 3.4%), dizziness (10.6% versus 1.5%), nausea (9.9% versus 3.2%), and fatigue (7.1% versus 4.3%). Given that flibanserin is a centrally acting agent, higher rates of CNS-centered events are not surprising, said Krychman.

Prescribing information for flibanserin includes a boxed warning about a risk of hypotension and syncope in women who drink alcohol while taking the drug or who take other drugs that are moderate or strong inhibitors of the CYP3A4 pathway. Additionally, the FDA mandated that all prescribers complete a Risk Evaluation and Mitigation Strategies training program.

Krychman questioned the design of an FDA-required study that led to the boxed warning. The study, conducted during daytime, predominantly involved men, and participants were required to consume 3 ounces of distilled spirits, two beers, or two glasses of wine immediately prior to taking flibanserin. Krychman pointed out that the drug is supposed to be taken at bedtime.

"If you take the medication, you have more than a 60% chance of responding," he said. "Those that respond, as determined by prescription refills and during the clinical trial, continue to take the drug. These people stay on the medication."

Patients who took the medication as prescribed in the evening had no CNS effects in the morning, Krychman continued. Additionally, a study of automobile driving showed that women who took flibanserin at night had better driving performance the next day.

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