A Comparison of Lithium and T ₃ Augmentation Following Two Failed Medication Treatments for Depression: A STAR*D Report

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 (T ₃ ) 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 T ₃ (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 T ₃ 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 T ₃ 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 T ₃ augmentation suggest that it has slight advantages over lithium augmentation for depressed patients who have experienced several failed medication trials.