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

Rena Cooper-Kazaz, Jeffrey T Apter, Revital Cohen, Leonid Karagichev, Said Muhammed-Moussa, Daniel Grupper, Taly Drori, Michael E Newman, Harold A Sackeim, Benjamin Glaser, Bernard Lerer
Archives of General Psychiatry 2007, 64 (6): 679-88

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, placebo-controlled 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 microg/d for 1 week; 40-50 microg/d thereafter) or sertraline plus placebo for 8 weeks.

MAIN OUTCOME MEASURES: 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.

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 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.

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.

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