Better sexual acceptability of agomelatine (25 and 50 mg) compared with paroxetine (20 mg) in healthy male volunteers. An 8-week, placebo-controlled study using the PRSEXDQ-SALSEX scale

Abstract

Sexual dysfunction (SD) is a common and underestimated effect of antidepressants. Healthy volunteers are the most adequate group to study this adverse event avoiding influence of depression itself. Sexual acceptability of agomelatine (a melatonergic agonist and 5HT(2C) antagonist) paroxetine and placebo by using the Psychotropic-Related Sexual Dysfunction Salamanca Sex Questionnaire (PRSEXDQ-SALSEX) was explored. A total of 92 healthy male volunteers were randomised to agomelatine (25 or 50 mg), paroxetine 20 mg or placebo for 8 weeks. SD, defined as at least one sexual impairment in one of the following PRSEXDQ-SALSEX items (decreased libido, delayed orgasm/ejaculation, anorgasmia/no ejaculation and erectile dysfunction), was evaluated at baseline and after 2, 4 and 8 weeks. At the last post-baseline assessment, SD was significantly lower in each agomelatine group (22.7% on 25 mg and 4.8% on 50 mg) than in the paroxetine group (85.7%; p < 0.0001). In the placebo group, 8.7% of volunteers reported a SD. The percentages of volunteers with moderate or severe SD were 4.5% for agomelatine 25 mg, 4.8% for agomelatine 50 mg, 61.9% for paroxetine 20 mg and 0% in the placebo group (p < or = 0.0001 agomelatine versus paroxetine). There is a much lower risk of having SD with agomelatine than paroxetine in healthy male volunteers, which confirms the better sexual acceptability profile of agomelatine compared with the SSRIs.

The impact of severe mental disorders and psychotropic medications on sexual health and its implications for clinical management

“…Some novel antidepressants may have a relatively low propensity for adverse effects on sexual function 73 . Randomized controlled trials with agomelatine suggest it has fewer adverse effects on sexual functioning than some other antidepressants, which is probably due to its antagonist effects at the 5-HT2C receptor, rather than the agonist effects at melatonin receptors [74][75][76][77] , although the absence of effects on nitrergic relaxation of corpus cavernosum smooth muscle may also be relevant 78 .…”

Emerging antidepressants to treat major depressive disorder

“…During a 6-month period, relapse was significantly lower in patients on continued agomelatine therapy compared to placebo (Goodwin et al, 2009). Additionally, this drug has less sexual side effects than SSRIs (Montejo et al, 2010). However, problematic are the transient elevations in liver enzymes, which is one reason why agomelatine is not approved for use in the US.…”

Agomelatine: a review for general practitioners

“…This was borne out in an eight-week, placebo-controlled study in healthy volunteers, that revealed that sexual dysfunction was significantly lower in those taking agomelatine, compared to those taking paroxetine. 41 In a 12-week study in depressed patients, agomelatine showed a superior sexual side-effect profile compared to venlafaxine. 23 Transient and mild nausea and dizziness are the most common adverse reactions, and these usually occur in the first two weeks and generally do not lead to cessation of treatment.…”