Discontinuation of maintenance selective serotonin reuptake inhibitor monotherapy after 5 years of stable response: a naturalistic study.

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.

Continuation versus discontinuation of lithium in recurrent bipolar illness: a naturalistic study.

OBJECTIVES: Lithium's efficacy in prophylaxis of mood episodes in bipolar disorder (BD) is well established in the clinical trial setting, but may be less robust in routine clinical practice. We compared illness recurrence in bipolar patients naturalistically continued on or discontinued from lithium after an extended period of clinical stability on lithium monotherapy, and evaluated other potential risk factors for relapse. METHODS: We followed 213 patients who were stable for 2 years on lithium monotherapy following resolution of acute symptoms marking their last manic episode. Based upon patient preference and clinical judgment, 159 patients were continued on lithium monotherapy and 54 patients were slowly discontinued. Survival differences between the continued and discontinued groups were assessed using the Kaplan-Meier product limit method, and risk factors for relapse were evaluated in Cox proportional hazards regression. RESULTS: Patients continued on lithium prophylaxis experienced risk of recurrence equivalent to a third of that suffered by discontinued patients during the first year of treatment (0.15 versus 0.45), and significant survival differences persisted throughout follow-up. Median survival time to illness recurrence for patients continued on lithium was 7.33 years [95% confidence interval (CI) 5.67-9.67]; that for patients discontinued from lithium was 1.33 years (95% CI 0.33-2.33). After controlling for all significant covariates, lithium discontinuation was associated with a hazard ratio of 4.85. Inter-episode manic and depressive symptoms conferred increased risk for subsequent recurrence of illness in both groups, while lower lithium levels recorded during the two years of clinical stability preceding study onset were protective. CONCLUSIONS: Despite considerable rates of illness recurrence in both groups, those who continued on lithium sustained markedly lower rates of recurrence over a lengthy follow-up period. Lithium discontinuation in BD after successful maintenance monotherapy is not advisable. If discontinuation is considered, lithium levels previously required to maintain clinical stability, and breakthrough or residual mood symptoms experienced during remission, should inform clinical decision making.