Combined Treatment With Sertraline and Liothyronine in Major Depression: A Randomized, Double-Blind, Placebo-Controlled Trial

Arch Gen Psychiatry. 2007 Jun;64(6):679-88. doi: 10.1001/archpsyc.64.6.679.


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.

Trial registration: NCT00158990.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Depressive Disorder, Major / diagnosis
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / psychology
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Middle Aged
  • Placebos
  • Psychiatric Status Rating Scales / statistics & numerical data
  • Serotonin Uptake Inhibitors / adverse effects
  • Serotonin Uptake Inhibitors / therapeutic use*
  • Sertraline / adverse effects
  • Sertraline / therapeutic use*
  • Thyroid Function Tests
  • Thyrotropin / blood
  • Treatment Outcome
  • Triiodothyronine / adverse effects
  • Triiodothyronine / therapeutic use*


  • Placebos
  • Serotonin Uptake Inhibitors
  • Triiodothyronine
  • Thyrotropin
  • Sertraline

Associated data