Combined treatment with sertraline and liothyronine in major depression - A randomized, double-blind, placebo-controlled trial

Background: Antidepressant treatments that achieve a higher remission rate than those currently available are urgently needed. The thyroid hormone triiodothyronine may potentiate antidepressant effects. Objective: To determine the antidepressant efficacy and safety of liothyronine sodium (triiodothyronine) when administered concurrently with the selective serotonin reuptake inhibitor sertraline hydrochloride to patients with major depressive disorder. Design: Double-blind, randomized, 8-week, placebocontrolled trial. Setting: Outpatient referral centers. Patients: A total of 124 adult outpatients meeting unmodified DSM-IV criteria for major depressive disorder without psychotic features. Interventions: Patients were randomized to receive sertraline hydrochloride (50 mg/d for 1 week; 100 mg/d thereafter) plus liothyronine sodium (20-25 mu g/d for 1 week; 40-50 mu g/d thereafter) or sertraline plus placebo for 8 weeks. Main Outcome Measures: The primary outcome measure was categorical response to treatment (>= 50% decrease in scores on the 21-item Hamilton Rating Scale for Depression from baseline to study end point). Remission rate (final Hamilton Rating Scale for Depression score, >= 6) was a secondary outcome measure. Results: Intent-to-treat Hamilton Rating Scale for Depression response rates were 70% and 50% in the sertraline-liothyronine and sertraline-placebo groups, respectively (P=.02; odds ratio, 2.93; 95% confidence interval, 1.23-7.35); remission rates were 58% with sertralinehothyronine and 38% with sertraline-placebo (P=.02; odds ratio, 2.69; 95% confidence interval, 1.16-6.49). Baseline T-3 values were lower in patients treated with sertraline-liothyronine who had remissions than in those without remissions t(48)=3.36; P <.002). Among patients treated with sertraline-liothyronine, remission was associated with a significant decrease in serum thyrotropin values (F-1,(73)=4.00; P < 05). There were no significant effects of liothyronine supplementation on frequency of adverse effects. Conclusions: These results demonstrate enhancement of the antidepressant effect of sertraline by concurrent treatment with liothyronine without a significant increase in adverse effects. The antidepressant effect of liothyronine may be directly linked to thyroid function.