Introduction: Depression is a public health problem for which treatment is done with the use of antidepressant drugs, which should be used with caution due to its side effects and potential drug interactions. Objective: To identify and classify the main potential drug interactions between antidepressants and other drugs. Materials and methods: The research was conducted with patients that use antidepressants and received it from the Basic Health Unity of the city of Sao Jose do Inhacora, RS, Brazil. The subjects were located by searching the database of appointments that took place from December 2013 to January 2014. The interviews were conducted at their homes by using a data collection instrument developed by the authors and validated by a pilot study. Potential drug interactions were researched in the Micromedex® database. The missing interactions on that database were further investigated on books regarding drug interactions and were classified for risk assessment as being of high, moderate and low importance. Results: A total of 88 patients were interviewed, the mean age was 56.68±16.36 years old. A total of 127 potential drug interactions were detected and 42 (47.72%) patients were directly subjected to it, with a mean of 5.90±2.73 per patient. Regarding the risk assessment, the interactions were classified as high in 69 (54.33%), moderate in 53 (41.73%) and low in 5 (3.94%). Conclusion: This study demonstrates the occurrence of potential medical interactions in a significant portion of the patients, as well as the self medication practice, which also represents a risk for the users. Therefore, it is important that the pharmacist is part of the multidisciplinary team, aiming to minimize the pharmacological related errors and to improve the quality of life of the patients.