Triiodothyronine Augmentation in the Treatment of Refractory Depression: A Meta-analysis

doi:10.1001/archpsyc.1996.01830090090013

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Vol. 53 No. 9, September 1996

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Triiodothyronine Augmentation in the Treatment of Refractory Depression

A Meta-analysis

Ronnie Aronson, MD; Hilary J. Offman; Russel T. Joffe, MD; C. David Naylor, MD, DPhil

Arch Gen Psychiatry. 1996;53(9):842-848.

Abstract

Background
Several trials have addressed the efficacy of liothyronine sodiumtherapy in euthyroid, nonpsychotic depressed patients refractoryto tricyclic antidepressant therapy. We undertook a meta-analysisof these trials.

Methods
The MEDLINE database (1966 to May 1995) and published referencelists were examined for controlled clinical trials of triiodothyronineaugmentation in euthyroid patients with refractory depression.Quality assessment and data abstraction were performed independentlyby two reviewers. Results were aggregated three ways: the relativeresponse rate compared with controls, accepting each trial'sdefinition of clinical response; absolute improvement in responserates; and improvements in depression scores, analyzed as continuousvariables without a prespecified threshold for clinical response.

Results
Aggregating eight studies with a total of 292 patients, patientstreated with triiodothyronine augmentation were twice as likelyto respond as controls (relative response, 2.09; 95% confidenceinterval [CI], 1.31 to 3.32; P=.002). This corresponded to a23.2% absolute improvement in response rates (95% CI, 4.5% to41.9%; P=.02). Improvements in depression scores were moderatelylarge (standardized effect size, 0.62; P<.001). However,study quality was uneven, and results were statistically heterogeneous.Among the four randomized double-blind studies, pooled effectswere not significant (relative response, 1.53; 95% CI, 0.70to 3.35; P=.29), but one study with negative results accountedfor most of the intertrial heterogeneity in results.

Conclusions
Triiodothyronine augmentation may be an effective empiricalmethod of increasing response rates and decreasing depressionseverity scores in a subgroup of patients with depression refractoryto tricyclic antidepressant therapy, but the total number ofpatients randomized was small, and additional placebo-controlleddata are required for a definitive verdict. Since therapeutictrends now favor other drugs, future trials might usefully examinetriiodothyronine augmentation with selective serotonin reuptakeinhibitors or compare potentiation strategies, eg, lithium vstriiodothyronine, for managing refractory depression. Such trialswould benefit from much larger sample sizes than those reviewedhere.

Author Affiliations

From the Departments of Medicine (Drs Aronson and Naylor), Psychiatry (Dr Offman), and Behavioural Science (Dr Naylor) and the Sunnybrook Unit, Clinical Epidemiology and Health Care Research Program (Dr Naylor), University of Toronto (Ontario); Department of Psychiatry, McMaster University, Hamilton, Ontario (Dr Joffe); and the Institute for Clinical Evaluative Sciences, Toronto (Dr Naylor).

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