Improvement in subjective sleep in major depressive disorder with a novel antidepressant, agomelatine: randomized, double-blind comparison with venlafaxine.

OBJECTIVE: Patients with major depressive disorder (MDD) experience sleep disturbances that may be worsened by some antidepressant drugs early in treatment. The aim of this study was to assess the subjective quality of sleep of patients receiving agomelatine, a new antidepressant with melatonergic MT(1) and MT(2) receptor agonist and 5-HT(2C) antagonist properties, compared with that of patients receiving venlafaxine, a serotonin-norepinephrine reuptake inhibitor.

METHOD: This double-blind, randomized study involved 332 patients with MDD (DSM-IV criteria), lasted 6 weeks, and compared the effects of agomelatine 25-50 mg/day and venlafaxine 75-150 mg/day, with a possible dose adjustment at 2 weeks. Subjective sleep was assessed with the Leeds Sleep Evaluation Questionnaire (LSEQ), and the main efficacy criterion was the "getting to sleep" score. Antidepressant efficacy was assessed with the 17-item Hamilton Rating Scale for Depression (HAM-D) and the Clinical Global Impressions (CGI) global improvement scale. The study was performed between November 2002 and June 2004.

RESULTS: After 6 weeks, the antidepressant efficacy of agomelatine was similar to that of venlafaxine. The LSEQ "getting to sleep" score was significantly better with agomelatine (70.5 +/- 16.8 mm) than with venlafaxine (64.1 +/- 18.2 mm); the between-treatment difference at the last visit was 6.36 mm (p = .001), and the difference was already significant at week 1. Secondary sleep items, including LSEQ quality of sleep (p = .021), sleep awakenings (p = .040), integrity of behavior (p = .024), and sum of HAM-D items 4, 5, and 6 (insomnia score) (p = .044), were also significantly improved compared to venlafaxine, as was the CGI global improvement score (p = .016). Incidence of adverse events was 52.1% with agomelatine and 57.1% with venlafaxine, and withdrawals due to adverse events were more common with venlafaxine than with agomelatine (13.2% vs. 4.2%).

CONCLUSION: Agomelatine showed similar antidepressant efficacy with earlier and greater efficacy in improving subjective sleep than venlafaxine in MDD patients.