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Discontinuation of Maintenance Selective Serotonin Reuptake Inhibitor Monotherapy After 5 Years of Stable Response: A Naturalistic Study

J Clin Psychiatry 2008;69(11):1811-1817

Objective: Selective serotonin reuptake inhibitors (SSRIs) are effective treatments of major depressive disorder (MDD), but data to guide the duration of maintenance therapy in community settings are limited. We assessed whether extending maintenance beyond 5 years provided additional benefit and identified other predictors of outcome.

Method: All patients treated at an urban community outpatient clinic between June 1993 and September 2005 were considered for inclusion in this study. Based upon patient preference and clinician judgment, 60 patients with DSM-IV MDD elected to continue, and 27 patients to discontinue, SSRI treatment after 5 years of clinical stability on maintenance monotherapy in a community clinic. Differences in relapse risk were assessed using the Kaplan-Meier product limit method, and risk factors were evaluated in Cox proportional hazards regression, based on up to 8 years of illness course.

Results: Subjects who continued on SSRI treatment experienced a survival probability of maintaining remission during the first year, which was twice that of discontinued subjects (0.79 vs. 0.40), and survival differences persisted for over 30 months. Median survival time until relapse for patients who continued SSRIs was 38 months, exceeding the 10-month survival time of patients who discontinued. After controlling for significant covariates, the hazard ratio for SSRI discontinuation was 4.9. Residual depressive symptoms conferred increased relapse risk, while age, gender, SSRI type and dose, and prior depressive episodes did not predict relapse.

Conclusion: After 5 years of maintenance monotherapy for MDD, SSRI discontinuation in a community setting is associated with a far poorer illness course than continued maintenance. Discontinuation of long-term maintenance is most likely to be successful in patients with minimal residual symptoms, and discontinued patients should be carefully monitored.