The present analysis assesses the 24-week antidepressant efficacy and safety of agomelatine 10, 25 and 25–50 mg versus placebo in outpatients suffering from moderate to severe Major Depressive Disorder (MDD).

In this phase III, international, randomized, double-blind trial, 549 patients were randomized in four parallel groups: agomelatine 10 mg (n=133), agomelatine 25 mg (n=138), agomelatine 25–50 mg (n=137) or placebo (n=141).

In the FAS (N=547), at last post-baseline assessment, there were significant and incremental differences (E(SE)) on mean HAM-D total score in favor of each agomelatine dose regimen vs placebo: 10mg – 4.51(1.06) (p<0.0001); 25mg – 7.74 (1.05) (p< 0.0001); 25–50mg – 7.72 (1.05) (p< 0.0001).

The response rate (decrease in HAM-D total score ≥ 50% from baseline) was higher on each agomelatine group: 63.6% on 10mg, 78.3% on 25 mg, 77.2% on 25–50mg than on placebo group (41.8%), p<0.001, p< 0.0001 and p< 0.0001 respectively.

The remission rate (HAM-D total score<7) was higher on each agomelatine group: 38.6% on 10mg, 55.8% on 25mg and 57.4% on 25-50 mg groups versus 22.0% on placebo, p=0.003, p<0.0001, p<0.0001 respectively.

Headache and nausea were the most frequent emergent adverse events on agomelatine irrespective of the dose regimen (in at least 5% of patients).

One patient on agomelatine 10mg, 2 patients on agomelatine 25mg and 2 patients on agomelatine 50 mg versus none on placebo had transaminases increase (>3 ULN). All recovered.

These results show the long-term antidepressant effect over 24 weeks of 3 dose regimens of agomelatine in MDD patients.