OBJECTIVES: To compare medication persistence and concomitant MDD drug use in patients prescribed i) branded desvenlafaxine, ii) other branded selective serotonin re-uptake inhibitors (SSRIs) and selective serotonin-norepinephrine re-uptake inhibitors (SNRIs), and iii) generic SSRIs/SNRIs (escitalopram, venlafaxine, citalopram, fluvoxamine, sertraline, fluoxetine and paroxetine). METHODS: MDD patients (ICD-9-CM codes 296.2, 296.3) with ≥2 prescription fills for branded desvenlafaxine or other SSRIs/SNRIs and 12 months continuous enrollment pre-index (where first fill date was index date) were identified from the MarketScan Commercial Claims and Encounters Database (2009-2013). Treatment persistence (time to treatment discontinuation, defined as a prescription gap≥ 45 days) was assessed using Kaplan-Meier curves and Cox proportional model. Concomitant drug use among study groups was examined. RESULTS: Of 273,514 identified patients, 14,379 initiated branded desvenlafaxine (mean age 46 years; 30% with psychiatric comorbidities [PC]), 50,937 other branded SSRIs/SNRIs (48 years; 31% PC), and 208,198 generic SSRIs/SNRIs (47 years; 29% PC). Median time to discontinuation for branded desvenlafaxine was longer than either branded or generic SSRIs/SNRIs groups (40.7 [95% CI: 39.3, 42.0] vs. 28.9 [28.4, 29.1] vs. 33.4 [33.1, 33.7] weeks). After adjustment, patients treated with other branded SSRIs/SNRIs (HR=1.31, P <0.001) or generic SSRIs/SNRIs (HR=1.11, P <0.001) were more likely to discontinue than branded desvenlafaxine patients. Concomitant drug use was higher among branded desvenlafaxine (44%) compared to other branded (40%) and generic (36%) SSRIs/SNRIs groups. The most frequent concomitant drugs used were atypical antidepressants alone (37%), followed by antipsychotics alone (18%). CONCLUSIONS: Patients prescribed branded desvenlafaxine were more persistent than other branded or generic SSRIs/SNRIs groups and had a higher prevalence of concomitant drug use than other patients.  The higher concomitant drug use did not appear to be driven by differences in psychiatric comorbidity burden. Results suggest a better ability to stay on treatment with branded desvenlafaxine compared to other SSRI/SNRI medications.