Major depressive disorder may respond to monotherapy with monoamine oxidase inhibitors (MAOIs) or tianeptine. Literature search showed no reports of MAOIs combined with tianeptine. The method included was clinical case history. A 59-year-old woman had partial improvement of depression with the MAOI tranylcypromine combined with topiramate, trazodone and ziprasidone. The patient had further improvement of depression symptoms after addition of tianeptine. No adverse events were evident. The combination of MAIOs and tianeptine may be effective for refractory major depressive disorder.