Introduction: Antidepressants are used primarily in the management of depressive and anxiety disorders. The occurrence of adverse drug reactions (ADRs) to antidepressants is a major challenge as it influences patient compliance. Aim: The aim of this study was to find out the ADR profile of antidepressant drugs in a mental health institute in Odisha. Materials and Methods: This is a cross sectional observational study conducted in Department of Pharmacology in collaboration with Mental Health Institute (Centre of Excellence) S.C.B Medical College and Hospital, Cuttack from September 2017 to September 2019. Patients who received at least one antidepressant drug were included in the study irrespective of age and sex. Data were collected by interviewing the patients or attendants and on detection of ADR, it was recorded on suspected ADR reporting form designed by PvPI. Causality, severity and preventability of ADRs were assessed by, WHO-UMC causality assessment, modified Hartwig-Siegel Scale and modified Schumock-Thornton criteria respectively. Results: Out of 180 patients taking antidepressants, ADRs were reported in 24% of patients, with either possible or probable causality. None were labelled as certain. ADRs were observed in 50% of patients who received TCAs and among 34.5% who received polytherapy. Insomnia (27%), fatigue (17%) and agitation (13%) were most common ADRs. Most of the ADRs were of mild severity (91%) and not preventable (84%). Conclusion: Insomnia, fatigue and agitation were among most common ADRs. There was increased chance of ADRs with polytherapy and use of TCAs. Most ADRs were mild and not preventable.