OBJECTIVE: Sertraline maintenance therapy effectively delays recurrence of major depressive disorder in adult diabetic patients when data are examined across all age-groups. A secondary analysis was performed to assess this effect in younger and older subsets of patients. RESEARCH DESIGN AND METHODS: Younger (aged <55 years, n = 85) and older (aged > or =55 years, n = 67) subsets were identified from a multicenter, double-blind, placebo-controlled, maintenance treatment trial of sertraline in diabetic participants who achieved depression recovery with open-label sertraline treatment. Cox proportional hazards models were used to determine differences in time to depression recurrence between treatment arms (sertraline or placebo) for each age subset and between age subsets for each treatment. RESULTS: In younger subjects, sertraline conferred significantly greater prophylaxis against depression recurrence than placebo (hazard ratio 0.37 [95% CI 0.20-0.71]; P = 0.003). Benefits of sertraline maintenance therapy were lost in older participants (0.94 [0.39-2.29]; P = 0.89). There was no difference in time to recurrence for sertraline-treated subjects between age subsets (P = 0.65), but older subjects had a significantly longer time to recurrence on placebo than younger subjects (P = 0.03). CONCLUSIONS: While sertraline significantly increased the time to depression recurrence in the younger diabetic participants, there was no treatment effect in those aged > or =55 years because of a high placebo response rate. Further research is necessary to determine the mechanisms responsible for this effect and whether depression maintenance strategies specific for older patients with diabetes should be developed.