A Double-Blind Comparison of Sexual Functioning, Antidepressant Efficacy, and Tolerability Between Agomelatine and Venlafaxine XR

TLDR

Sexual dysfunction is common in major depressive disorder and worsens with antidepressant use, reducing treatment compliance. The study compared agomelatine and venlafaxine XR on sexual function in depressed patients. A 12‑week, double‑blind, multicenter trial enrolled 276 adults, randomizing them to agomelatine 50 mg or venlafaxine XR up to 150 mg/d, with analyses focused on sexually active patients and those achieving remission. Agomelatine produced significantly less sexual dysfunction and fewer adverse‑event discontinuations than venlafaxine XR, while remission rates were comparable, indicating a superior sexual side‑effect profile.

Abstract

Impaired sexual function is associated with major depressive disorder in the untreated state and is often more prevalent during antidepressant therapy, which frequently results in poor treatment compliance. In this double-blind, multicenter study, the effects of agomelatine (an MT1 and MT2 agonist and 5HT-2C antagonist) and venlafaxine XR on sexual function were compared using the Sex Effects Scale in depressed patients. A total of 276 male and female patients received either agomelatine (50 mg) or venlafaxine XR (titrated to a target dose of 150 mg/d) for 12 weeks. Those who were sexually active at baseline (n = 193) and those who, in addition, achieved remission (n = 111) were defined a priori for analyses of change in sexual function. Treatment-emergent sexual dysfunction was significantly less prevalent among patients who received agomelatine, and venlafaxine XR was associated with significantly greater deterioration on the Sex Effects Scale domains of desire and orgasm. Both treatments resulted in equivalently high rates of remission (agomelatine, 73%; venlafaxine XR, 66.9%), although fewer patients in the agomelatine group discontinued treatment because of adverse events (agomelatine, 2.2%, vs venlafaxine XR, 8.6%). Agomelatine seems to be an efficacious antidepressant with a superior sexual side effect profile compared with venlafaxine XR, although superiority to placebo was not evaluated in this trial.