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Background: Major depressive disorder (MDD) is the most common disorder in our community. Hypericum perforatumm, is a herb with a long application history in treating depression. A controlled study to evaluate the effects of this herbal medicine in Iran did not exist. Objectives: This study aimed to assess the effect of Hypericum perforatom (perforan), in combination with tricyclic antidepressants in MDD treatment. Materials and Methods: The present study was a placebo-controlled double blind rand-omized clinical trial including 40 patients with major depressive disorder who referred to Psychiatric Clinic and Golestan Hospital in 2011. Patients were randomly distributed in 4 blocks with 10 patients in each. 5 out of 10 patients took medicine (group I) and the others received placebo (group II)