Short-term venlafaxine v. lithium monotherapy for bipolar type II major depressive episodes: effectiveness and mood conversion rate

Br J Psychiatry. 2016 Apr;208(4):359-65. doi: 10.1192/bjp.bp.115.169375. Epub 2016 Feb 18.


Background: Controversy exists over antidepressant use in bipolar II depression.

Aims: To compare the safety and effectiveness of antidepressantv.mood stabiliser monotherapy for bipolar type II major depressive episodes.

Method: Randomised, double-blind, parallel-group, 12-week comparison of venlafaxine (n= 65)v.lithium (n= 64) monotherapy in adult out-patients (trial registration numberNCT00602537).

Results: Primary outcome - venlafaxine produced a greater response rate (67.7%)v lithium (34.4%,P<0.001). Secondary outcomes - venlafaxine produced a greater remission rate (58.5%v 28.1%,P<0.001); greater decline in depression symptom scores over time (β = -5.32, s.e. = 1.16, χ(2)= 21.19,P<0.001); greater reduction in global severity scores over time (β = -1.05, s.e. = 0.22, w(2)= 22.33,P<0.001); and greater improvement in global change scores (β = -1.31, s.e. = 0.32, χ(2)= 16.95,P<0.001) relative to lithium. No statistically significant or clinically meaningful differences in hypomanic symptoms were observed between treatments.

Conclusions: These findings suggest that short-term venlafaxine monotherapy may provide effective antidepressant treatment for bipolar II depression without a statistically significant increase in hypomanic symptoms relative to lithium.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antidepressive Agents / adverse effects
  • Antidepressive Agents / therapeutic use
  • Bipolar Disorder / drug therapy*
  • Double-Blind Method
  • Female
  • Humans
  • Lithium Compounds / adverse effects*
  • Lithium Compounds / therapeutic use*
  • Male
  • Middle Aged
  • Psychiatric Status Rating Scales
  • Treatment Outcome
  • Venlafaxine Hydrochloride / adverse effects*
  • Venlafaxine Hydrochloride / therapeutic use*
  • Young Adult


  • Antidepressive Agents
  • Lithium Compounds
  • Venlafaxine Hydrochloride

Associated data