An Open Study of Triiodothyronine Augmentation of Selective Serotonin Reuptake Inhibitors in Treatment-Resistant Major Depressive Disorder

Dan V. Iosifescu, M.D.; Andrew A. Nierenberg, M.D.; David Mischoulon, M.D.; Roy H. Perlis, M.D.; George I. Papakostas, M.D.; Julie L. Ryan, B.A.; Jonathan E. Alpert, M.D.; and Maurizio Fava, M.D.

Objective: In an open trial, we investigated the efficacy of triiodothyronine (T₃) adjuvant to selective serotonin reuptake inhibitors (SSRIs) in subjects with major depressive disorder (MDD) resistant to SSRI treatment.

Method: Twenty subjects who met DSM-IV criteria for MDD (mean ± SD age = 44.3 ± 10.3 years; 55% [N = 11] women) and had failed to respond to a course of treatment of at least 8 weeks with an SSRI antidepressant were enrolled in a 4-week open-label augmentation treatment with T₃ 50 mg/day. Atypical and melancholic subtypes of MDD were diagnosed using Structured Clinical Interview for DSM-IV Axis I Disorders criteria. We administered the 17-item Hamilton Rating Scale for Depression (HAM-D-17) 4 times during the study (which was conducted between 2001 and 2003).

Results: During T₃ augmentation, the severity of depression decreased from an initial mean ± SD HAM-D-17 score of 20.5 ± 3.6 to a final HAM-D-17 score of 14.0 ± 7.1 (p < .001). Seven subjects (35.0%) were treatment responders (HAM-D-17 reduction >= 50%), and 6 subjects (30.0%) achieved clinical remission (final HAM-D-17 <= 7). The 5 subjects with atypical depression experienced significantly (p < .01) greater clinical improvement (final HAM-D-17 scores 6.6 ± 1.8 vs. 16.4 ± 4.5), and higher rates of treatment response (100% [5/5] vs. 13.3% [2/15]) and remission (80.0% [4/5] vs. 13.3% [2/15]), compared to subjects with nonatypical MDD. The 8 subjects with melancholic MDD experienced significantly (p < .05) greater depression severity at the end of the study compared to nonmelancholic MDD subjects (final HAM-D-17 scores = 18.3 ± 6.6 vs. 11.1 ± 6.1).

Conclusion: Triiodothyronine augmentation of SSRIs may be a promising treatment strategy in SSRI-resistant MDD, particularly in subjects with the atypical MDD subtype.

(J Clin Psychiatry 2005;66:1038-1042)

Received Sept. 29, 2004; accepted Feb. 3, 2005. From the Depression Clinical and Research Program, Massachusetts General Hospital, Harvard Medical School, Boston.

This study was supported by a National Alliance for Research on Schizophrenia and Depression (NARSAD) Young Investigator Award (Dr. Iosifescu) and a Clinical Investigator Training Program Fellowship from Harvard/Massachusetts Institute of Technology Division of Health Science and Technology, in collaboration with Pfizer Inc (Dr. Iosifescu).

Preliminary findings from this study were presented at the American College of Neuropsychopharmacology (ACNP) 42nd Annual Meeting, San Juan, Puerto Rico, 2003, and at the American Psychiatric Association 157th Annual Meeting, New York, N.Y., 2004.

Financial disclosure appears at the end of the article.

Corresponding author and reprints: Dan V. Iosifescu, M.D., Massachusetts General Hospital, 50 Staniford St., Suite 401, Boston, MA 02114 (e-mail: diosifescu@partners.org).