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Triiodothyronine Addition to Paroxetine in the Treatment of Major Depressive Disorder

Departments of Endocrinology and Metabolism (B.C.A., J.P.B., E.F., W.M.W.), Psychiatry (J.H., A.H.S.), and Cardiology (J.G.P.T.), Academic Medical Centre, University of Amsterdam, 1100 DE Amsterdam, The Netherlands; and Department of Psychiatry (R.v.D., W.J.G.H.), Vrjie Universiteit Medical Centre, 1081 HV Amsterdam, The Netherlands

Address all correspondence and requests for reprints to: Bente C. Appelhof, M.D., Academic Medical Center of the University of Amsterdam, Department of Endocrinology and Metabolism, F5-161, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands. E-mail: b.c.appelhof{at}amc.uva.nl.

There is evidence that thyroid hormone T₃ increases serotonergic neurotransmission. Therefore, T₃ addition to antidepressants may improve treatment response in major depression. In nonrefractory depression, T₃ addition to tricyclic antidepressants indeed accelerates treatment response. Current therapeutic practice favors selective serotonin reuptake inhibitors. This is the first study to investigate the efficacy of T₃ addition to paroxetine in major depression.

One hundred thirteen patients with major depressive disorder were randomly assigned to 8 wk of double-blind outpatient treatment with low-dose T₃ (25 µg), high-dose T₃ (25 µg twice daily), or placebo in addition to paroxetine 30 mg daily.

A total of 106 patients started treatment and were included in the outcome analysis. Response rate after 8 wk (reduction of Hamilton Rating Scale for Depression score 50%) was 46% in all three treatment arms (P = 0.99). T₃ addition did not accelerate clinical response to paroxetine, nor was an effect of T₃ found when only women were analyzed. Patients on T₃ addition reported more adverse events than patients on placebo comedication.

In conclusion, these results do not support a role for T₃ addition to selective serotonin reuptake inhibitors in the treatment of nonrefractory major depressive disorder. On the contrary, more adverse reactions occurred in T₃-treated patients.

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