Lithium carbonate versus cognitive therapy as sequential combination treatment strategies in partial responders to antidepressant medication: an exploratory trial

J Clin Psychiatry. 2003 Apr;64(4):439-44. doi: 10.4088/jcp.v64n0414.


Background: Partial antidepressant response is associated with increased rates of relapse. Despite increasing evidence that full symptomatic remission is the optimal goal of antidepressant therapy, there have been few comparisons between disparate treatment approaches to achieve this goal.

Method: Forty-four patients with DSM-IV major depressive disorder (MDD) who had a partial response (17-item Hamilton Rating Scale for Depression [HAM-D-17] score of 8-15) during open-label antidepressant treatment for 8 to 14 weeks were randomly assigned to receive cognitive therapy (CT) or lithium augmentation (LA) for a further 8 weeks using a single-blind design. Antidepressant medication was continued throughout the study. Subjects were also reassessed 4 weeks after discontinuation of LA or CT. Patients were enrolled in this study beginning September 1996 and follow-up for all patients was completed in December 2000.

Results: Although LA or CT did not significantly decrease symptom severity during sequential combination therapy, there was a significant decrease in HAM-D-17 scores 4 weeks later in LA-treated subjects compared with CT-treated subjects (p =.04). This resulted in 32% of patients achieving remission status, although between-group differences were not significantly different (38% in the LA group compared with 26% in the CT group, p =.39).

Conclusion: Despite methodological limitations, this preliminary study provides justification for both combination treatments. An adequately powered, randomized, controlled trial to evaluate the relative merits of combination psychotherapy and augmentation of pharmacotherapy in patients with partially remitted MDD is required.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antidepressive Agents / therapeutic use*
  • Cognitive Behavioral Therapy
  • Combined Modality Therapy
  • Depressive Disorder / diagnosis
  • Depressive Disorder / drug therapy
  • Depressive Disorder / therapy*
  • Female
  • Follow-Up Studies
  • Humans
  • Lithium Carbonate / therapeutic use*
  • Male
  • Middle Aged
  • Personality Inventory
  • Psychiatric Status Rating Scales
  • Secondary Prevention
  • Severity of Illness Index
  • Single-Blind Method
  • Treatment Outcome


  • Antidepressive Agents
  • Lithium Carbonate