Combined treatment with sertraline and liothyronine in major depression: a randomized, double-blind,...

Antidepressant treatments that achieve a higher remission rate than those currently available are urgently needed. The thyroid hormone triiodothyronine may potentiate antidepressant effects.

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.

Double-blind, randomized, 8-week, placebo-controlled trial.

Outpatient referral centers.

A total of 124 adult outpatients meeting unmodified DSM-IV criteria for major depressive disorder without psychotic features.

Patients were randomized to receive sertraline hydrochloride (50 mg/d for 1 week; 100 mg/d thereafter) plus liothyronine sodium (20-25 microg/d for 1 week; 40-50 microg/d thereafter) or sertraline plus placebo for 8 weeks.

The primary outcome measure was categorical response to treatment (> or =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, < or =6) was a secondary outcome measure.

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 sertraline-liothyronine 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.

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.