The outcome of depression can be affected after chronic use of antidepressants, because of the spectrum of side effects affecting compliance and quality of life. Among the most disabling side effects are sleep disturbances and sexual dysfunction.

Agomelatine, with its unique pharmacological profile acting as an agonist at melatonergic receptors and as an antagonist at 5-HT2C receptors, improves sleep and does not affect sexual functioning in major depressive disorder. In one study, agomelatine 25 mg, increased slow-wave sleep and normalized its distribution throughout the night (P<0.05) without altering REM sleep. In another study, agomelatine 25-50mg, compared with venlafaxine 75-150 mg, showed similar antidepressant efficacy and demonstrated significant sleep improvement (LSEQ questionnaire) as early as from the first week of treatment (P=0.007 for getting off to sleep and P=0.015 for quality of sleep). This improvement was maintained throughout the entire 6-week treatment period, with a parallel improvement in daytime alertness.

A comparison of sexual functioning in depressed patients treated with agomelatine or venlafaxine indicated that agomelatine 50 mg had a better sexual profile than venlafaxine XR 150 mg in remitted patients after 12 weeks of treatment on both orgasm and preorgasm measures; both treatments showed comparable antidepressant efficacy. To confirm the favourable effects of agomelatine on sexual functions, a study in healthy volunteers has been carried out and these results will be discussed.

In conclusion, agomelatine is a novel antidepressant that ameliorates disturbed sleep and leaves sexual functioning unaffected, thus improving both depressive symptoms and quality of life of depressed patients.