OBJECTIVES: Depressive disorders affect ~35 million US adults annually. A large US health plan offers some members a “Refill and Save Program” (RSP), with discounted copayments for desvenlafaxine (DSV) and extended-release venlafaxine (VENXR) when refilled within 30 days after previous fill run-out. This study compared adherence between RSP and non-RSP cohorts. METHODS: This retrospective claims database study examined adult commercial members with ≥1 claim for DSV or VENXR from October 1, 2009 – March 31, 2010; the first claim date was index date. Members with schizophrenia were excluded. Members were continuously enrolled for 6 months pre-index and 9 months post-index. Proportion of days covered (PDC) on index antidepressant was modeled with ordinary least-squares regression, controlling for index antidepressant, naïve antidepressant use, demographic and plan characteristics. Subset analysis was conducted on naïve and continuing index antidepressant users and on subjects with no change in post-index RSP exposure. RESULTS: The study population included 46,138 members with mean age 48±12 years and 75.3% female, divided between RSP (n=28,925) and non-RSP (n=17,213): 21.4% were naïve to their index antidepressants. Mean PDC was 69% in RSP, 65% in non-RSP (p<0.001). Regression results showed PDC was 6.5 percentage points higher (p<0.001) in the RSP versus non-RSP cohort. PDC in RSP cohort was 8.2 percentage points higher (p<0.001) among naïve index antidepressant users, and 6.4 percentage points higher (p<0.001) among continuing users. Analyses on those with no change in post-index RSP exposure yielded similar significant results but with smaller effect. CONCLUSIONS: The RSP cohort, versus non-RSP, had higher index antidepressant PDC. These results suggest that copayment discounts may have a positive impact on adherence to desvenlafaxine and extended-release venlafaxine HCl.