OBJECTIVES: This study examined patterns of adherence, switching, and discontinuation, in major depressive disorder (MDD) patients initiating antidepressant medication (ADM) therapy. METHODS: Depressed patients recently initiating an ADM were identified from a large pharmacy benefits manager database. Eligible patients were invited to participate by phone or mail and enrolled patients completed RESULTS: Of 2,412 patients screened, 591 were enrolled. Average age was 40.4 years (standard deviation=12.1), 82.4% of participants were women, and 87.6% were white. At Week 4 (n=483), 39.4% were classified as low adherers with 31 (6.4%) patients having discontinued ADM for reasons including side effects (n=14, 45.2%), feeling better (n=5, 16.1%), cost (n=5, 16.1%), and lack of efficacy (n=4, 12.9%). There were 27 (5.6%) patients who switched by Week 4. Of these, 12 (44.4%) switched due to side effects, 11 (40.7%) due to lack of efficacy, and 3 (11%) due to cost. By week 12 (n=425), 33 additional patients had discontinued ADM citing similar reasons as those at Week 4. Of 43 patients who reported switching at Week 4 or Week 12, 15 (34.9%) cited side effects, 16 (37.2%) cited lack of efficacy, and 4 (9.3%) cited cost. CONCLUSIONS: In this real-world, 12-week study of MDD patients initiating ADM, adherence to ADM was low. Switching and discontinuing ADM were common within the 12-weeks period and were primarily attributed to side effects and lack of efficacy.