Safety and effectiveness of continuation antidepressant versus mood stabilizer monotherapy for relapse-prevention of bipolar II depression: A randomized, double-blind, parallel-group, prospective study

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.

Trial registration: ClinicalTrials.gov NCT00602537.

Keywords: Antidepressant; Bipolar II depression; Bipolar II disorder; Clinical trial. ClinicalTrials.gov identifier: NCT00602537; Lithium; Mood conversion; Relapse-prevention; Venlafaxine.

Copyright © 2015 Elsevier B.V. All rights reserved.

Figures

Figure 1

CONSORT diagram of subjects assigned to continuation venlafaxine or lithium