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A Comparison of Lithium and T₃ Augmentation Following Two Failed Medication Treatments for Depression: A STAR*D Report

STAR*D Study Team

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.

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