Rif S El-Mallakh1, Paul A Vöhringer2, Michael M Ostacher3, Claudia F Baldassano4, Niki S Holtzman5, Elizabeth A Whitham5, Sairah B Thommi5, Frederick K Goodwin6, S Nassir Ghaemi7. 1. Department of Psychiatry, University of Louisville, Louisville, KY, United States. 2. Mood Disorders Program, Department of Psychiatry, Tufts Medical Center, Boston, MA, United States; Clinic University Hospital, University of Chile, Santiago, Chile, United States. 3. Department of Psychiatry & Behavioral Sciences, Stanford School of Medicine, Palo Alto, CA, United States. 4. Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, United States. 5. Mood Disorders Program, Department of Psychiatry, Tufts Medical Center, Boston, MA, United States. 6. Department of Psychiatry, The George Washington University, Washington, DC, United States. 7. Mood Disorders Program, Department of Psychiatry, Tufts Medical Center, Boston, MA, United States; Tufts University School of Medicine, Boston, MA, United States.
Abstract
BACKGROUND: The use of antidepressants in rapid-cycling bipolar disorder has been controversial. We report the first randomized clinical trial with modern antidepressants on this topic. METHODS: As part of the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study, we analyzed, as an a priori secondary outcome, rapid cycling as a predictor of response in 68 patients randomized to continue vs. discontinue antidepressant treatment, after initial response for an acute major depressive episode. Outcomes assessed were percent time well and total number of episodes. All patients received standard mood stabilizers. RESULTS: In those continued on antidepressants (AD), rapid cycling (RC) subjects experienced 268% (3.14/1.17) more total mood episodes/year, and 293% (1.29/0.44) more depressive episodes/year, compared with non-rapid cycling (NRC) subjects (mean difference in depressive episodes per year RC vs. NRC was 0.85 ± 0.37 (SE), df = 28, p = 0.03). In the AD continuation group, RC patients also had 28.8% less time in remission than NRC patients (95% confidence intervals (9.9%, 46.5%), p = 0.004). No such differences between RC and NRC subjects were seen in the AD discontinuation group (Table 1). Analyses within the rapid-cycling subgroup alone were consistent with the above comparisons between RC and NRC subjects, stratified by maintenance antidepressant treatment, though limited by sample size. CONCLUSIONS: In an a priori analysis, despite preselection for good antidepressant response and concurrent mood stabilizer treatment, antidepressant continuation in rapid-cycling was associated with worsened maintenance outcomes, especially for depressive morbidity, vs. antidepressant discontinuation.
RCT Entities:
BACKGROUND: The use of antidepressants in rapid-cycling bipolar disorder has been controversial. We report the first randomized clinical trial with modern antidepressants on this topic. METHODS: As part of the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study, we analyzed, as an a priori secondary outcome, rapid cycling as a predictor of response in 68 patients randomized to continue vs. discontinue antidepressant treatment, after initial response for an acute major depressive episode. Outcomes assessed were percent time well and total number of episodes. All patients received standard mood stabilizers. RESULTS: In those continued on antidepressants (AD), rapid cycling (RC) subjects experienced 268% (3.14/1.17) more total mood episodes/year, and 293% (1.29/0.44) more depressive episodes/year, compared with non-rapid cycling (NRC) subjects (mean difference in depressive episodes per year RC vs. NRC was 0.85 ± 0.37 (SE), df = 28, p = 0.03). In the AD continuation group, RC patients also had 28.8% less time in remission than NRC patients (95% confidence intervals (9.9%, 46.5%), p = 0.004). No such differences between RC and NRC subjects were seen in the AD discontinuation group (Table 1). Analyses within the rapid-cycling subgroup alone were consistent with the above comparisons between RC and NRC subjects, stratified by maintenance antidepressant treatment, though limited by sample size. CONCLUSIONS: In an a priori analysis, despite preselection for good antidepressant response and concurrent mood stabilizer treatment, antidepressant continuation in rapid-cycling was associated with worsened maintenance outcomes, especially for depressive morbidity, vs. antidepressant discontinuation.
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