A single blind comparison of lithium and lamotrigine for the treatment of bipolar II depression

J Affect Disord. 2008 Dec;111(2-3):334-43. doi: 10.1016/j.jad.2008.02.004. Epub 2008 Mar 20.


Background: Treatment studies are lacking for patients with bipolar II disorder (BDII). The objective of this study was to compare lamotrigine (LTG) and lithium (Li) monotherapy for the treatment of BDII depression.

Methods: Patients with BDII acute depression were randomized to open-label monotherapy with LTG or Li, and evaluated by trained raters blinded to treatment. Patients were titrated to 200 mg/day of LTG over 8 weeks or at least 900 mg/day of Li over 2 weeks (serum level 0.6-1.2 mEq/L), and seen biweekly for 16 weeks. The primary outcome variable was change in the Hamilton Depression Rating Scale 17-item (Ham-D(17)), evaluated using mixed effects random regression.

Results: Both groups showed significant improvement from baseline to endpoint on the Ham-D(17) (p<0.0001), with no between group differences (p=0.95). Seventy-two percent of the population was rapid cycling by DSM-IV criteria. No differences in response were noted between rapid cyclers and non-rapid cyclers. Early termination for any cause was 42%. The Li group reported significantly more side effects, although drop-out due to side effects did not differ between groups.

Limitations: This study was limited by an open treatment design, a lack of placebo arm, and uneven treatment groups.

Conclusions: Lamotrigine and lithium were effective monotherapy for BDII depression, with comparable response and remission rates. Naturalistic design and lack of placebo limit conclusions, though patient history indicated long standing depression unlikely to be alleviated by time. Patients who received Li reported more side effects, but this did not appear to impact drop-out rates.

Publication types

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

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Aged
  • Ambulatory Care
  • Anticonvulsants / adverse effects
  • Anticonvulsants / therapeutic use*
  • Bipolar Disorder / diagnosis
  • Bipolar Disorder / drug therapy*
  • Bipolar Disorder / psychology
  • Diagnostic and Statistical Manual of Mental Disorders
  • Drug Administration Schedule
  • Female
  • Humans
  • Lamotrigine
  • Lithium Compounds / adverse effects
  • Lithium Compounds / therapeutic use*
  • Male
  • Middle Aged
  • Patient Dropouts
  • Psychiatric Status Rating Scales
  • Severity of Illness Index
  • Single-Blind Method
  • Survival Analysis
  • Treatment Outcome
  • Triazines / adverse effects
  • Triazines / therapeutic use*


  • Anticonvulsants
  • Lithium Compounds
  • Triazines
  • Lamotrigine