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Objective: The aim of this study is to define the clinical features that affect the antidepressant treatment response by comparing the cases that responded and did not respond to the antidepressant treatment. Methods: Among the patients admitted to the GATA Department of Psychiatry, the ones who were diagnosed with major depressive disorder and have given antidepressant treatment were included to the study. Sociodemographic information form, SCID-I, SCID-II, and Hamilton Depression Scale (HAM-D) were used for the initial assessment. HAM-D scale was repeated at the second, fourth and sixth weeks of the treatment. The cases, whose HAM-D scale scores were reduced 50% or more, were defined as the responders to antidepressant treatment and were compared with non-responders based on their clinical features. Results: At the end of the sixth week of the treatment, 73 (83.9%) of the 87 depression cases responded to the treatment and 14 (16.1%) of them did not respond. The severity of the depression was higher and there were more comorbid Axis-I and Axis-II diagnoses in the non-responders group compared to the responders group. There were no significant differences between the two groups in terms of the comorbid physical illnesses, the number of depression episodes and the age of onset of the disease. Conclusion: As a result, the severity of the depression and the comorbidity of Axis-I and Axis-II diagnoses were determined as the clinical features which negatively affect the response to the antidepressant treatment. These clinical features could be evaluated as possible indicators of poorer outcomes of antidepressant treatments and therefore considering other treatment options might be important at the beginning of the treatment.