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Objectives: To determine and explore the factors that contribute towards non-compliance to antidepressants among patients with major depressive disorder. Methodology: A longitudinal multicenter study was conducted from April to October 2019 to October 2020 in several psychiatric clinics in Pakistan. All patients with diagnosed depression as per ICD 10 Criteria, who were above the age 18 years, gave consent to take part in the study were eligible for the study. Patients with a history of traumatic brain injury, aged &lt; 18 years were excluded from the study. Compliance to treatment was measured through self-report and prescription refill data. Results: A total of 820 patients were included in this study. A median age of 33.0 (18-67) was observed with the majority of female patients. Out of the total study population of 820 patients, 284 (34.6%) reported non-compliance to the treatment. The cause of non-compliance was significantly associated with therapeutic management. The majority of the patients who were on tricyclic antidepressants (TCAs) stopped taking medication because of lack of improvement in their symptoms. About 100 (55.90%) patients on SSRis reported lack of efficacy for non-compliance however, when antidepressants were combined with cognitive behavioral therapy the reported rate of lack of efficacy reduced to 32.9% Conclusion: The current study shows that the foremost reason for non-compliance was lack of efficacy among patients.  Keywords: anxiety, antidepressants, cognitive behavioral therapy, efficacy, depression, tricyclic antidepressants

Factors leading to Non-Compliance to Antidepressants Among Patients with Major Depressive Disorder: A Cohort Study from Pakistan