A comparison of lithium and T3 augmentation following two failed medication treatments for depression: A STAR*D report

Andrew A. Nierenberg, Maurizio Fava, Madhukar H. Trivedi, Stephen R. Wisniewski, Michael E. Thase, Patrick J. McGrath, Jonathan E. Alpert, Diane Warden, James F. Luther, George Niederehe, Barry Lebowitz, Kathy Shores-Wilson, A. John Rush

Research output: Contribution to journalArticlepeer-review

376 Scopus citations


Objective: More than 40% of patients with major depressive disorder do not achieve remission even after two optimally delivered trials of antidepressant medications. This study compared the effectiveness of lithium versus triiodothyronine (T3) augmentation as a third-step treatment for patients with major depressive disorder. Method: A total of 142 adult outpatients with nonpsychotic major depressive disorder who had not achieved remission or who were intolerant to an initial prospective treatment with citalopram and a second switch or augmentation trial were randomly assigned to augmentation with lithium (up to 900 mg/day; N=69) or with T3 (up to 50 μg/day; N=73) for up to 14 weeks. The primary outcome measure was whether participants achieved remission, which was defined as a score ≤7 on the 17-item Hamilton Depression Rating Scale. Results: After a mean of 9.6 weeks (SD=5.2) of treatment, remission rates were 15.9% with lithium augmentation and 24.7% with T3 augmentation, although the difference between treatments was not statistically significant. Lithium was more frequently associated with side effects (p=0.045), and more participants in the lithium group left treatment because of side effects (23.2% versus 9.6%; p=0.027). Conclusions: Remission rates with lithium and T3 augmentation for participants who experienced unsatisfactory results with two prior medication treatments were modest and did not differ significantly. The lower side effect burden and ease of use of T3 augmentation suggest that it has slight advantages over lithium augmentation for depressed patients who have experienced several failed medication trials.

Original languageEnglish (US)
Pages (from-to)1519-1530
Number of pages12
JournalAmerican Journal of Psychiatry
Issue number9
StatePublished - Sep 2006
Externally publishedYes

ASJC Scopus subject areas

  • Psychiatry and Mental health


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