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

Tara M. Pundiak, M.D.; Brady G. Case, M.D.; Eric D. Peselow, M.D.; and Loretta Mulcare, B.S.E.

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.


(J Clin Psychiatry 2008;69:1811-1817. Online Ahead of Print November 4, 2008.)

Received Feb. 25, 2008; accepted June 18, 2008. From Freedom from Fear, Staten Island, N.Y.

Preliminary data were presented at the American Psychiatric Association 58th Institute on Psychiatric Services, October 5-8, 2006, New York, N.Y., and at the 160th annual meeting of the American Psychiatric Association, May 19-24, 2007, San Diego, Calif.

The authors acknowledge the staff at Freedom from Fear for their help compiling these data.

Dr. Case is currently with the Department of Adolescent Psychiatry, New York University School of Medicine, New York; and the Statistics and Services Research Division, Nathan S. Kline Institute for Psychiatric Research, Orangeburg, N.Y.

Dr. Case has received research support from the American Psychiatric Association through a grant funded by AstraZeneca and from the American Academy of Child and Adolescent Psychiatry through a grant funded by Eli Lilly. Dr. Peselow has participated in speakers/advisory boards for Pfizer and Forrest. Dr. Pundiak and Ms. Mulcare report no financial affiliations or other relationships relevant to the subject of this article.

Corresponding author and reprints: Tara M. Pundiak, M.D., PSC 476 Box 76, FPO, AP 96322 (e-mail: