title: 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).
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Jay D
authors.initials: JD
authors.lastname: Amsterdam
authors.affiliation: 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.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Lorenzo-Luaces
authors.affiliation: 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.
authors.forename: Irene
authors.initials: I
authors.lastname: Soeller
authors.affiliation: 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.
authors.forename: Susan Qing
authors.initials: SQ
authors.lastname: Li
authors.affiliation: Department of Family Medicine and Community Health, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Jun J
authors.initials: JJ
authors.lastname: Mao
authors.affiliation: 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.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: DeRubeis
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000523:psychology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D018020:Lithium Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D011446:Prospective Studies; D055502:Secondary Prevention / Q000706:statistics & numerical data*; D016896:Treatment Outcome; D000069470:Venlafaxine Hydrochloride / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D018020:Lithium Compounds; D000069470:Venlafaxine Hydrochloride
keywords: Antidepressant; Bipolar II depression; Bipolar II disorder; Clinical trial. ClinicalTrials.gov identifier: NCT00602537; Lithium; Mood conversion; Relapse-prevention; Venlafaxine