There has been limited research into defining what constitutes an adequate first-line antidepressant trial in elderly patients. The authors report the outcome of extended, high-dosage sertraline treatment in a sample of nursing home residents experiencing residual significant depressive symptoms after 10 weeks of treatment with sertraline at a final dosage of 100 mg/day. Subjects who had a Hamilton Depression Rating Scale score > or = 12 after 10 weeks of treatment with sertraline were eligible for the 8-week open-label extension phase, which involved titrating the sertraline dosage to 200 mg/day. The cumulative response rate was 52% for the extension phase, compared with 37% for the acute phase. Examining acute phase nonresponders, 39% responded during the extension phase. Rates of discontinuation due to adverse events were comparable in the 2 phases. Our findings suggest that an extended trial or high dosages of sertraline may benefit some depressed elderly patients with persistent depression after acute treatment.