A BSTRACT Background: Antidepressant medications are primarily used in the management of depression and various anxiety disorders. Antidepressant medications are known to cause adverse drug reactions (ADRs). Reporting ADRs can help in the rational use of medication and better patient drug management. Objective: The aim of this study was to monitor the incidence and nature of ADRs to antidepressant medications in a psychiatric outpatient setting of a secondary care hospital of the UAE. Materials and Methods: It was a cross-sectional study conducted in the psychiatric outpatient setting of a secondary care hospital. Patients attending psychiatry outpatient department and prescribed with antidepressant medications were included. All clinical side effects or ADRs noted by physician and reported by patients were documented and assessed according to causality, severity, and preventability scales. Results: A total of 131 patients were screened for the presence or occurrence of ADRs. During the study duration, an aggregate of 29 patients reported at least one ADR. Incidence of suspected ADR to antidepressant medications was found to be 22.1%. Most commonly documented suspected ADR was found to be weight gain in eight (18.1%) patients followed by somnolence in four (9.1%) patients. Escitalopram was the most common drug implicated with ADR in 13 (29.6%) patients followed by fluoxetine in 6 (13.6%) patients. According to World Health Organization-The Uppsala Monitoring Centre causality assessment, the predominance of the suspected ADRs was of “possible” type in 27 (61%) patients, and “mild” in severity in 40 (91%) patients, and “not preventable” in 37 (84%) patients. A statistically significant association ( P = 0.019) was observed only between the presence of drug-interaction and the occurrence of ADR (relative risk: 0.429, confidence interval: 0.211–0.872). Conclusion: Most of the suspected ADRs related to antidepressants were “mild,” “predictable,” and “not preventable” in nature. Continuous monitoring may help in identifying, reducing, and preventing the risk of ADRs.