Objective: Recommendations for treatment of chronic major depressive disorder (cMDD) are mostly based on clinical experiences and on the literature on treatment-resistant depression (TRD) but not on a systematic review of the literature. Method: We conducted a systematic review of 10 randomized controlled trials (RCTs), with 17 comparisons between antidepressants (ADs), psychotherapy, or the combination of both interventions. Results: The best evidence is for the combination of psychotherapy and ADs, and especially for the combination of the cognitive behavourial analysis system of psychotherapy and ADs. Evidence is very weak for both ADs alone and psychotherapy alone. Assessment of TRD was mostly absent in the studies. Conclusion: The best treatment for cMDD is a combination of psychotherapy and ADs. However, there is a lack of well-performed RCTs in both ADs and psychotherapy and their combination for cMDD. Therefore, the conclusions are preliminary. Psychothérapie, antidépresseurs, et leur combinaison pour le trouble dépressif majeur chronique: une revue systématique