This Article  • References  • Full text PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Social Bookmarking   What's this?

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 sodium therapy in euthyroid, nonpsychotic depressed patients refractory to tricyclic antidepressant therapy. We undertook a meta-analysis of these trials.

Methods
The MEDLINE database (1966 to May 1995) and published reference lists were examined for controlled clinical trials of triiodothyronine augmentation in euthyroid patients with refractory depression. Quality assessment and data abstraction were performed independently by two reviewers. Results were aggregated three ways: the relative response rate compared with controls, accepting each trial's definition of clinical response; absolute improvement in response rates; and improvements in depression scores, analyzed as continuous variables without a prespecified threshold for clinical response.

Results
Aggregating eight studies with a total of 292 patients, patients treated with triiodothyronine augmentation were twice as likely to respond as controls (relative response, 2.09; 95% confidence interval [CI], 1.31 to 3.32; P=.002). This corresponded to a 23.2% absolute improvement in response rates (95% CI, 4.5% to 41.9%; P=.02). Improvements in depression scores were moderately large (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 effects were not significant (relative response, 1.53; 95% CI, 0.70 to 3.35; P=.29), but one study with negative results accounted for most of the intertrial heterogeneity in results.

Conclusions
Triiodothyronine augmentation may be an effective empirical method of increasing response rates and decreasing depression severity scores in a subgroup of patients with depression refractory to tricyclic antidepressant therapy, but the total number of patients randomized was small, and additional placebo-controlled data are required for a definitive verdict. Since therapeutic trends now favor other drugs, future trials might usefully examine triiodothyronine augmentation with selective serotonin reuptake inhibitors or compare potentiation strategies, eg, lithium vs triiodothyronine, for managing refractory depression. Such trials would benefit from much larger sample sizes than those reviewed here.

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).

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Evidence-based guidelines for treating depressive disorders with antidepressants: A revision of the 2000 British Association for Psychopharmacology guidelines
Anderson et al.
J Psychopharmacol 2008;22:343-396.
ABSTRACT  

Combined Treatment With Sertraline and Liothyronine in Major Depression: A Randomized, Double-blind, Placebo-Controlled Trial
Cooper-Kazaz et al.
Arch Gen Psychiatry 2007;64:679-688.
ABSTRACT | FULL TEXT  

A Comparison of Lithium and T3 Augmentation Following Two Failed Medication Treatments for Depression: A STAR*D Report
Nierenberg et al.
Am. J. Psychiatry 2006;163:1519-1530.
ABSTRACT | FULL TEXT  

Daily Variations in Type II Iodothyronine Deiodinase Activity in the Rat Brain as Controlled by the Biological Clock
Kalsbeek et al.
Endocrinology 2005;146:1418-1427.
ABSTRACT | FULL TEXT  

New drugs, old problems: REVISITING... PHARMACOLOGICAL MANAGEMENT OF TREATMENT-RESISTANT DEPRESSION
Cowen
Adv. Psychiatr. Treat. 2005;11:19-27.
ABSTRACT | FULL TEXT  

Drug treatment of depression: reflections on the evidence
Anderson
Adv. Psychiatr. Treat. 2003;9:11-20.
ABSTRACT | FULL TEXT  

Randomised controlled trials investigating pharmacological and psychological interventions for treatment-refractory depression: Systematic review
STIMPSON et al.
Br. J. Psychiatry 2002;181:284-294.
ABSTRACT | FULL TEXT  

Slower Treatment Response in Bipolar Depression Predicted by Lower Pretreatment Thyroid Function
Cole et al.
Am. J. Psychiatry 2002;159:116-121.
ABSTRACT | FULL TEXT  

Progress in the Battle With the Black Dog: Advances in the Treatment of Depression
Nemeroff
Am. J. Psychiatry 2001;158:1555-1557.
FULL TEXT  

Does Thyroid Supplementation Accelerate Tricyclic Antidepressant Response? A Review and Meta-Analysis of the Literature
Altshuler et al.
Am. J. Psychiatry 2001;158:1617-1622.
ABSTRACT | FULL TEXT  

Enhanced Spontaneous Locomotor Activity in Bovine GH Transgenic Mice Involves Peripheral Mechanisms
Bohlooly-Y et al.
Endocrinology 2001;142:4560-4567.
ABSTRACT | FULL TEXT  

Cognitive therapy and social functioning in chronic depressionAuthor's reply
Ito et al.
Br. J. Psychiatry 2001;178 :477-478.
FULL TEXT  

Evidence-based guidelines for treating depressive disorders with antidepressants: a revision of the 1993 British Association for Psychopharmacology guidelines
Anderson et al.
J Psychopharmacol 2000;14:3-20.
ABSTRACT  

Low Levels of Transthyretin in the CSF of Depressed Patients
Sullivan et al.
Am. J. Psychiatry 1999;156:710-715.
ABSTRACT | FULL TEXT  

Fortnightly review: Drug treatment of depression
Spigset and Mårtensson
BMJ 1999;318:1188-1191.
FULL TEXT  

Chronic Clomipramine and Triiodothyronine Increase Serotonin Levels in Rat Frontal Cortex In Vivo: Relationship to Serotonin Autoreceptor Activity
Gur et al.
J. Pharmacol. Exp. Ther. 1999;288:81-87.
ABSTRACT | FULL TEXT