UPDATED October 24, 2016 // Currently available antidepressants may aggravate sexual dysfunction and make depression worse, a new survey of US adults with major depressive disorder (MDD) suggests.
"This survey provides a new window into the lives of those trying to manage and live with major depressive disorder and paints a comprehensive picture of the consequences of antidepressant treatments that don't also address sexual dysfunction," Anita H. Clayton, MD, professor and chair of psychiatry and neurobehavioral sciences at the University of Virginia School of Medicine in Charlottesville, said in a statement.
Roughly 1000 US adults currently receiving antidepressant drug therapy for MDD participated in the Sexual Symptoms and Side Effects in Depression (SEXSED) survey, conducted online between September 28 and October 5, 2016.
The vast majority (88%) of respondents reported a loss of sexual desire, satisfaction, or sexual function. More than two thirds (68%) first experienced sexual problems as a symptom of their depression, and 17% first experienced sexual problems only after starting antidepressants.
Of those reporting sexual dysfunction, more than half (55%) saw no improvement or suffered further decline in sexual function since starting their current antidepressant treatment. Nearly three quarters (73%) of those with sexual dysfunction reported that it made depression worse.
The survey was conducted by independent market research consultancy Wakefield Research and was commissioned by Fabre-Kramer Pharmaceuticals, the developer of gepirone extended-release (Travivo), a still experimental and somewhat controversial antidepressant that has a unique mechanism of action that may avert the sexual side effects of currently available antidepressants, such as selective serotonin reuptake inhibitors (SSRIs).
Sexual side effects of antidepressants are a "significant concern for many patients," Dr Clayton noted in an interview with Medscape Medical News. "There have been any number of studies now showing that SSRIs can contribute to significant sexual dysfunction in multiple areas, including desire, arousal, and orgasmic function," she said.
Gepirone "doesn't have serotonin reuptake inhibitory effects at all. It works at the serotonin 5-HT1A receptor," Dr Clayton explained. "There are some antidepressants on the market that also have a 5-HT1A effect, but they also have serotonin reuptake inhibitory effects. So if gepirone were approved, it would be the first drug like this for depression. It's been a long and drawn out process to approval, but I think it is moving forward," she said.
Rocky Regulatory Road
As reported previously by Medscape Medical News, in December 2015, a US Food and Drug Administration (FDA) advisory committee voted against approving gepirone (9 to 4), concluding that the available data did not support its approval.
But the company appealed the decision, and in March of this year, the FDA Office of New Drugs notified the company that it had subsequently concluded that gepirone does demonstrate evidence of effectiveness in the short-term treatment of MDD.
"This decision overturns FDA's previous position and resolves an outstanding deficiency impeding approval of Travivo," the company said in a news release at the time.
But Natalie Compagni Portis, PsyD, MFT, who was a patient representative on the FDA advisory panel in 2015, remains unconvinced.
There remains a "significant lack of evidence that gepirone performs well" in the treatment of MDD, she told Medscape Medical News. "It did not perform better than placebo or better than other active comparators in most of the trials. Post hoc analysis did show limited benefit in a few trials, but the endpoints had been changed in the post hoc analysis," she noted.
"Furthermore, reduced risks [of sexual dysfunction] in light of ineffective treatment are irrelevant," Dr Portis said. "Sexual dysfunction is of meaningful and significant concern to patients weighing the cost/benefit balance, but benefit is primary. Without significant benefit with regard to the depression, the sexual side effects are not meaningful," she said. "I will say, though, that when considering taking antidepressants, patients do express concern about sexual side effects, and it is a real deterrent for some."
Dr Portis added that she is "disappointed to hear that FDA has gone against the review panel's recommendations, though this is not without precedent." She said she stands by her comments to Medscape and at the review meeting.
But in an email to Medscape Medical News, Fabre-Kramer CEO Stephen Kramer, MD, said, "The evidence shows that Travivo does perform well. It has two positive pivotal phase 3 trials, acknowledged as positive by the FDA."
For now, said Dr Clayton, ways to manage sexual side effects of current antidepressants vary and usually depend on the individual.
"Some people just want to wait and watch it, and maybe for about 5% to 10% of people, sexual function will get better over 4 to 6 months. That's a pretty small likelihood of being effective," she pointed out.
"We do try to change the medication in some cases. For someone who has started on an antidepressant and it worked for them but they had sexual dysfunction, it's generally pretty easy to change them to another medication. But for people who have not responded to any number of medications and are finally on something that is helpful, then they may want to have something added in to try to counteract the sexual side effects," Dr Clayton said.
Dr Clayton has financial relationships with Fabre-Kramer Pharmaceuticals, Takeda, Palatin Technologies, S1 Biopharma, and other pharmaceutical companies. Dr Portis has disclosed no relevant financial relationships.
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Cite this: Antidepressants Worsen Sexual Dysfunction and Depression? - Medscape - Oct 20, 2016.