Sustained efficacy of agomelatine 10 mg, 25 mg, and 25-50 mg on depressive symptoms and functional outcomes in patients with major depressive disorder. A placebo-controlled study over 6 months

This randomized placebo-controlled "dose relation study" was conducted in patients who met criteria for major depressive disorder, to evaluate the efficacy and safety of agomelatine during 24 weeks at 3 doses (i) low fixed dosage (10 mg/day, n=100 patients entered the extension period), (ii) fixed dosage (25 mg/day, n=111) and (iii) a flexible dosage with up-titration in case of insufficient improvement at week 2 (25-50 mg/day, n=115) versus placebo (n=85). Mood was evaluated using the Hamilton rating scale for depression (HAM-D17) and Clinical Global Impression (CGI) scale. The functional status was examined with the Sheehan Disability Scale (SDS). At last post-baseline assessment, there were significant placebo-agomelatine differences on mean HAM-D17 total scores in favour of each agomelatine dose regimen (4.51±1.06 points, p<0.0001 at 10 mg; 7.74±1.05 points, p<0.0001 at 25 mg and 7.72±1.05 points, p<0.0001 at 25-50 mg). The response rate according to HAM-D17 was significantly higher in patients taking agomelatine than those taking placebo (difference of 21.8% at 10mg p<0.001; 36.4% and 35.4% respectively at 25 mg and 25-50 mg, p<0.0001). The remitter rate was significantly higher in patients taking agomelatine than those taking placebo (difference of 16.7% at 10 mg p=0.003; 33.8% and 35.4% respectively at 25 mg and 25-50 mg, p<0.0001). The effects of agomelatine were corroborated by CGI scores. Agomelatine improved symptom-related functional impairment on all domains of the SDS scale for the fixed dose 25 mg, and the one step titration 25-50 mg dose regimen. Similar findings were obtained for all measures in the subgroup of severely depressed patients. All dose regimens of agomelatine were well tolerated and no unexpected adverse event was reported. Long term agomelatine treatment improves both mood symptoms and social and occupational functioning of moderately to severely depressed patients. There is a dose effect between 10 mg and higher dose regimens of agomelatine. The threshold dose of 25 mg for initiating treatment can be maintained over 6 months in depressed patients.