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A Randomized, Double-blind, Placebo-Controlled Trial

Rena Cooper-Kazaz, MD; Jeffrey T. Apter, MD; Revital Cohen, MA; Leonid Karagichev, MD; Said Muhammed-Moussa, MD; Daniel Grupper, MD; Taly Drori, MD; Michael E. Newman, PhD; Harold A. Sackeim, PhD; Benjamin Glaser, MD; Bernard Lerer, MD

Arch Gen Psychiatry. 2007;64(6):679-688.

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 µg/d for 1 week; 40-50 µg/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 sertraline-liothyronine and 38% with sertraline-placebo (P = .02; odds ratio, 2.69; 95% confidence interval, 1.16-6.49). Baseline T₃ values were lower in patients treated with sertraline-liothyronine who had remissions than in those without remissions (t₄₈ = 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.

Trial Registration  clinicaltrials.gov Identifier: NCT00158990

Author Affiliations: Biological Psychiatry Laboratory, Department of Psychiatry (Drs Cooper-Kazaz, Karagichev, Muhammed-Moussa, Drori, Newman, and Lerer and Ms Cohen), and Endocrinology and Metabolism Service, Department of Internal Medicine (Dr Glaser), Hadassah-Hebrew University Medical Center, Jerusalem, Israel; Global Medical Institutes, Princeton, NJ (Dr Apter); Be’er Ya’akov Mental Health Center, Be’er Ya’akov, Israel (Dr Grupper); and Department of Biological Psychiatry, New York State Psychiatric Institute, New York (Dr Sackeim).

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