After the initial response, the next goal is to ensure sustained remission with normal functioning and minimal residual depressive symptoms. During this phase, continued adherence to treatment is needed, which is easier if the patient perceives improvement and tolerates the treatment well. The efficacy of agomelatine, the first melatonergic antidepressant with an innovative mode of action, has been assessed in the long term in 4 studies:

1. (1) the 18-week extension phases of two short-term studies comparing agomelatine (25-50 mg/d) with venlafaxine (75-150 mg/d),

2. (2) a similar extension phase after 6 weeks of treatment versus sertraline 50-100 mg/d, and

3. (3) a specific 10-month placebo-controlled relapse prevention study.

At 6 months, more patients responded to treatment with agomelatine either in term of improvement in CGI-I scores as compared to venlafaxine (P< 0.05), or in terms of response rate on the HAM-D as compared to sertraline (P< 0.05). Agomelatine therefore appears to produce in more patients a relief of depressive symptoms than either SNRIs or SSRIs.

A meta-analysis showed that a higher percentage of agomelatine-treated patients completed the extension period of 6 months as compared with venlafaxine or sertraline suggesting that clinical improvement induced by agomelatine lead to a better compliance to treatment.

The antidepressant efficacy of agomelatine is maintained in the long term, as demonstrated by the prevention of risk of relapse by 56.3% versus placebo over a 10-month treatment period (p< 0.0001).

All these features make agomelatine, the option to consider for achieving a full recovery from major depressive disorder.