This study will assess efficacy, safety and tolerability of agomelatine (AGO178) 25 mg and 50 mg in patients with Major Depressive Disorder (MDD). This study includes an 8-week double-blind phase and a 52-week open-label phase.

Inclusion Criteria:

• Diagnosis of Major Depressive Disorder, single or recurrent episode, according to DSM-IV criteria
• HAM-D17 total score > or = 22 at Screening and Baseline
• CGI-Severity score > or = 4 at Screening and Baseline
• Only patients who complete the core protocol are eligible to participate in the Open-Label Extension Phase

Exclusion Criteria:

• History of bipolar disorder (I or II), schizophrenia, schizoaffective disorder, eating disorder, or obsessive compulsive disorder
• Any current Axis I disorder other than major depressive disorder which is the focus of treatment
• Substance or alcohol abuse in the last 30 days, dependence in the last 6 months
• Concomitant psychotropic medication, including herbal preparations and melatonin
• Psychotherapy of any type
• Female patients of childbearing potential who are not using effective contraception

Other protocol-defined inclusion/exclusion criteria may apply