Antidepressants are widely used to treat depression in Korea, however, only a few studies have focused on the provider of the treatment. The aim of the study is to compare the differences between patients who were prescribed antidepressants by psychiatrists and those who were prescribed antidepressants by non-psychiatrists in South Korea. Patients with a diagnosis of depressive disorder who had been newly prescribed antidepressants in 2012 were selected from the Health Insurance Review and Assessment Service database. They were classified into two groups depending on whether they received the antidepressant prescription from a psychiatrist or non-psychiatrist. Sociodemographic, clinical, and depression related cost has been investigated. Treatment resistant depression, which is defined as a failure of two antidepressant regimens to alleviate symptoms, was also investigated. Prescription adequacy was assessed based on whether a regimen was maintained for at least 4 weeks. Among the 834694 patients with pharmaceutically treated depression (PTD) examined in this study, 326122 (39.1%) were treated by psychiatrists. Patients who were treated by psychiatrists were younger and had more psychiatric comorbidities than those treated by non-psychiatrists. They had longer PTD duration (229.3 days vs. 103.0 days, p < 0.05) and a larger proportion of treatment resistant depression (9.3% of PTD) when compared to those patients treated by non-psychiatrists. The patients treated by psychiatrists had a smaller proportion of inadequate antidepressant use compared to those patients in the non-psychiatrist group (44.5% vs. 65.1%, p < 0.05). The costs related to depression corrected with PTD duration were higher in the nonpsychiatrist group (32214 won vs. 56001 won, p < 0.05). Patients who receive antidepressants from psychiatrists are patients with more severe, treatment-resistant depression. Psychiatrists prescribe antidepressants more adequately and cost-effectively than non-psychiatrists.