An open study of triiodothyronine augmentation of selective serotonin reuptake inhibitors in treatment-resistant major depressive disorder

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

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48 Scopus citations


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 μg/day. Atypical and melancholic sub-types 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.

Original languageEnglish (US)
Pages (from-to)1038-1042
Number of pages5
JournalJournal of Clinical Psychiatry
Issue number8
StatePublished - Aug 2005
Externally publishedYes


ASJC Scopus subject areas

  • Psychiatry and Mental health

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