Antidepressant medications are prescribed to treat depression and related psychiatric illnesses. In patients with depression, many categories of drugs are prescribed to treat clinical conditions and comorbidities. Hence, it is essential to screen such patients for potential drug interactions. The study aimed to assess the frequency of potential drug interactions (pDDIs) associated with antidepressant medications administered to the outpatients of the psychiatry department. This cross-sectional investigation was conducted in a psychiatry outpatient setting. Patients satisfying inclusion criteria were screened for pDDIs by reviewing the patients’ electronic case records. All the identified pDDIs were further evaluated using Micromedex database 2.0.A total of 131 eligible patients’ case records were reviewed. The frequency of pDDIs between antidepressants and other psychotropic medications, antidepressants and non-psychotropic medications, antidepressants,tobacco, antidepressants, and ethanol was 48.1%,9.2%, 7.6%, and 3.8%, respectively. Use of more than three medications [RR: 1.5; CI: 1.1-2.1], presence of total [RR: 7.9; CI: 1.1-52.5] as well as psychiatric polypharmacy [RR: 4.8; CI: 1.3-17.9] were identified as predisposing factors of pDDIs.The results of the multiple regression indicated that the model was a significant predictor of pDDIs (F[3, 127]= 6.368, p<0.01, R2 = 0.13). In comparison,psychiatric polypharmacy was the only variable contributing significantly to the model (B = -0.423, p<.05). Nearly fifty percent of patients taking antidepressant medications were found to have the potential for developing drug interactions. Review of treatment charts for psychotropic, non-psychotropic, and non-prescription medications, along with different medical conditions that patients suffer from and the social habits of patients,is essential to identify and resolve potential drug interactions in at-risk patients.