Jay D Amsterdam1, Lorenzo Lorenzo-Luaces2, Irene Soeller3, Susan Qing Li3, Jun J Mao4, Robert J DeRubeis2. 1. Depression Research Unit, Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania School of Medicine, Philadelphia, PA, USA. Electronic address: jamsterd@mail.med.upenn.edu. 2. Depression Research Unit, Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Department of Psychology, University of Pennsylvania, Philadelphia, PA, USA. 3. Depression Research Unit, Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Department of Family Medicine and Community Health, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. 4. Department of Family Medicine and Community Health, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Abstract
OBJECTIVE: Compare the safety and effectiveness of continuation antidepressant versus mood stabilizer monotherapy for preventing depressive relapse in bipolar II disorder. METHODS:Subjects ≥18 years old with bipolar II depression (n=129) were randomized to double-blind venlafaxine or lithium monotherapy for 12 weeks. Responders with a ≥50% reduction in depression score were continued for an additional 6 months of relapse-prevention monotherapy. Primary outcome was depressive relapse during continuation monotherapy. Secondary outcomes included sustained response rate from initiation of treatment to study end-point, relapse hazard, time to relapse, change in mania ratings, and frequency of treatment-emergent sub-syndromal hypomania and/or depressive episodes. RESULTS:Venlafaxine produced greater sustained response rate versus lithium (p<0.0001); however, there was no difference in relapse rate for venlafaxine (7.5%) versus lithium (26.7%) (p=0.079); relapse hazard (p=0.073), or time to relapse (p=0.090) between treatment conditions during continuation monotherapy. There were no group differences in mania rating scores over time and no difference in frequency or duration of syndromal or sub-syndromal hypomanic episodes. There were more sub-syndromal depressive episodes during lithium monotherapy (p=0.03). LIMITATIONS: Sample size was limited by the lower sustained response rate for lithium versus venlafaxine; study was not specifically powered to detect differences in treatment-emergent hypomanic or depressive episodes between groups. CONCLUSION: Results suggest that continuation venlafaxine monotherapy may provide similar prophylactic effectiveness relative to lithium, with no difference in treatment-emergent hypomanic episodes and without the need for frequent serum lithium level and metabolic monitoring. Larger, prospective trials are needed to confirm these observations.
RCT Entities:
OBJECTIVE: Compare the safety and effectiveness of continuation antidepressant versus mood stabilizer monotherapy for preventing depressive relapse in bipolar II disorder. METHODS: Subjects ≥18 years old with bipolar II depression (n=129) were randomized to double-blind venlafaxine or lithium monotherapy for 12 weeks. Responders with a ≥50% reduction in depression score were continued for an additional 6 months of relapse-prevention monotherapy. Primary outcome was depressive relapse during continuation monotherapy. Secondary outcomes included sustained response rate from initiation of treatment to study end-point, relapse hazard, time to relapse, change in mania ratings, and frequency of treatment-emergent sub-syndromal hypomania and/or depressive episodes. RESULTS:Venlafaxine produced greater sustained response rate versus lithium (p<0.0001); however, there was no difference in relapse rate for venlafaxine (7.5%) versus lithium (26.7%) (p=0.079); relapse hazard (p=0.073), or time to relapse (p=0.090) between treatment conditions during continuation monotherapy. There were no group differences in mania rating scores over time and no difference in frequency or duration of syndromal or sub-syndromal hypomanic episodes. There were more sub-syndromal depressive episodes during lithium monotherapy (p=0.03). LIMITATIONS: Sample size was limited by the lower sustained response rate for lithium versus venlafaxine; study was not specifically powered to detect differences in treatment-emergent hypomanic or depressive episodes between groups. CONCLUSION: Results suggest that continuation venlafaxine monotherapy may provide similar prophylactic effectiveness relative to lithium, with no difference in treatment-emergent hypomanic episodes and without the need for frequent serum lithium level and metabolic monitoring. Larger, prospective trials are needed to confirm these observations.
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