ED Drug May Help Antidepressant-Related Sexual Dysfunction

Deborah Brauser

February 07, 2013

Although use of adjunctive sildenafil (Viagra, Pfizer) by patients with antidepressant-induced sexual dysfunction is not associated with improvements in quality of life, it may improve libido and sexual drive, new research suggests.

In further analysis of the Sequenced Treatment Alternatives to Relieve Depression (Star*D) study, investigators examined a cohort of 102 male and female patients who had received antidepressants, who complained of sexual dysfunction, and who were then give sildenafil 50 mg to 100 mg.

Results showed that 1 year after treatment, there were no significant overall improvements in quality-of-life scores. However, there were improvements in "overall contentment," as well as in sexual interest and libido. Sildenafil is often used to improve male erectile and orgasmic dysfunction.

"Because we measured only libido and not erectile dysfunction, it is possible that the direct association between the use of sildenafil and improvement in quality of life went undetected," write Christina M. Dording, MD, from the Depression Clinical and Research Program at Massachusetts General Hospital in Boston, and colleagues.

"Further characterization of the effects...in depressed populations appears warranted," they write.

The study is published in the February issue of Annals of Clinical Psychiatry.

Further Analysis From Star*D

According to the researchers, 50% of all patients taking antidepressants experience treatment-induced sexual dysfunction.

Patients often report that this dysfunction affects their mood, self-esteem, and relationships. It also often leads to premature discontinuation of treatment.

The investigators hypothesized that "an effective form of treatment for this common side effect" would improve various quality-of-life measures.

"Previous research has explored sildenafil's effectiveness in treating various forms of erectile dysfunction, but there is no research supporting sildenafil's use for improving the quality of life," they write, noting that the medication also has not been shown to be superior to placebo for treating libido deficits.

The multisite Star*D study has been called "the largest depression study ever done outside the pharmaceutical industry" by top researchers.

In it, patients with major depressive disorder (MDD) received up to 4 successive treatment steps, beginning with citalopram and then switching to or augmenting with other medication or with cognitive therapy as needed.

For this analysis, 102 (68.6% men; mean age, 42.2 years) of the 2239 participants who achieved remission and were in Star*D's follow-up phase were assessed. These patients all reported antidepressant-induced sexual dysfunction and received 50-mg to 100-mg daily doses of sildenafil as needed for 1 year.

The 30-item Inventory of Depressive Symptoms (IDS-C) was used to measure sexual interest, the 17-item Hamilton Depression Rating Scale (HDRS) was used to measure libido, and the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) was used to measure sexual drive.

In addition, the Q-LES-Q was used to measure overall quality of life as well as specific factors, such as familial relationships, overall well-being and contentment, and satisfaction with sildenafil.

Improved Libido

Over time, "gradual improvements" were found in libido and sexual functioning in the patients receiving sildenafil.

In addition, significant associations were found between treatment use and improvement in libido item 14 score on the HDRS (P = .0002) and in sexual interest item 22 score on the IDS-C (P = .0004).

These improvements "peaked at 6 months of follow-up, with some reversion at months 9 and 12, although final scores were still improved over baseline," report the investigators. "The improvement was thus not found to be time dependent."

Sexual drive, as measured on the Q-LES-Q, also steadily improved during the 12-month follow-up period.

There were no significant overall improvements found for the specific quality-of-life factors measured with the Q-LES-Q. However, there was a significant time-related improvement in overall contentment (P = .0081) — and treatment satisfaction did increase over time.

Finally, overall quality-of-life scores significantly decreased as sexual function worsened (P < .0001).

"Despite no direct association with sildenafil use and quality-of-life scores, sildenafil may be a beneficial treatment for antidepressant-induced sexual dysfunction," write the investigators.

They note that a double-blind, placebo-controlled study is now needed to explore these potential benefits.

Been There, Done That?

However, H. George Nurnberg, MD, told Medscape Medical News that this statement is confusing — especially because he has led prospective studies of this type.

This includes a randomized controlled trial (RCT) published in JAMA in 2003 that showed improvements in erectile function after treatment with sildenafil in men with antidepressant-associated sexual dysfunction, and an RCT published in JAMA in 2008 showing that women with this type of dysfunction had a reduction in adverse sexual effects after sildenafil treatment.

"The types of studies the investigators are calling for have already been done," said Dr. Nurnberg, who is professor and interim chair in the Department of Psychiatry at the University of New Mexico in Albuquerque.

He added that the current analysis did try to identify an important issue: the overall effect on people from treatment-related adverse events.

"However, spin-offs of studies such as Star*D are somewhat hampered by the methodology and limitations of what the initial large, mega-studies were all about," he said.

"With Star*D, they were trying to see what the real-world effectiveness of using antidepressant treatment would be and to inform clinicians about an effective way to manage depression. And this group is now trying to look at one small aspect of that. They're trying to prune a couple branches off this very thick tree."

Puzzling Measures

In addition, he called the quality-of-life measures used in this analysis "puzzling," especially the focus on libido and sexual drive.

"These are issues that were measured really by proxy. In other words, they used an item in each of their depression scales. But what PDE5 [phosphodiesterase type 5] inhibitors like sildenafil do is treat erectile dysfunction and orgasm delay. They don't claim to affect sexual drive," said Dr. Nurnberg.

"So it's odd that [the researchers] would focus on these measures to evaluate whether the drug works. Loss of sexual interest or drive is a depression effect."

He added that there is probably some "halo effect" in that as sexual side effects improve, "patients do feel better."

"But it's hard to tease out what was sexual dysfunction and what was really an effect on depression change, because the investigators were really picking a measure for sildenafil treatment that is more a measure for depression improvement," he said.

Still, he noted that, as mentioned earlier, other studies have shown that sildenafil can improve sexual dysfunction in this patient population.

"This is probably the most evidence-based treatment for antidepressant-associated sexual dysfunction that's in the literature," said Dr. Nurnberg.

However, he noted that "in the real world," clinicians should ask their patients several questions first, including, "Did you have sexual dysfunction before you became depressed? If not, did it start with the depression and did it change with treatment?"

"It's important to be proactive about asking these questions. That will let you know if the dysfunction is due to something independent of depression, treatment, or both.

The initial Star*D study was funded by the National Institute of Mental Health/National Institutes of Health. The study authors report numerous potential conflicts, which are fully listed in the original article. Dr. Nurnberg has disclosed no relevant financial relationships.

Ann Clin Psychiatry. 2013;25:3-10. Abstract