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Endocrine Rounds Mood Disorders and the Thyroid Wednesday, March 16, 2005 Dr. Merrill Edmonds Iodothyronine selenocysteine deiodinases T3 production Hypothyroid & Depression Thyroid & Depression Abnormalities in Thyroid Axis • Standard Tests variable • • • • TRH stimulation • • • Blunted response in 25-30% Exaggerated response in 10% TRH levels in CSF increased • • Some studies suggest increase in free T4 and decrease in free T3 and others suggest the opposite Sick Euthyroid picture Increased incidence of thyroid antibodies? (TBII) No correlation with circulating TSH Transthyretin levels in CSF are low Thyroid & Depression Animal studies • • antidepressants increase deiodinases in rat brain increase T3 levels in brain Mood stabilizing agents • Lithium, carbamazepine, valproic acid • lower thyroid levels Thyroid hormone in depression Augmentation agents? • • • First used in 1958 Numerous studies of variable methodologic rigor Meta-analysis (1996) Triiodothyronine augmentation in the treatment of refractory depression. A meta-analysis. Aronson R, Offman HJ, Joffe RT, Naylor CD. – 8 studies with 292 patients – 2 fold improvement in response rate = 23% absolute improvement Thyroid hormone in depression Augmentation agents? • T3 better than T4? Joffe RT and Singer 1990 Psychiatry Research 53% response rate with T3 vs 19% with T4 • T4 in larger doses as effective as T3? Bauer et al 1998, Neuropsychopharmacology Rudas et al 1999, Biol Psychiatry Thyroid hormone in depression • Accelerate Tricyclic Response? • Meta-analysis (2001) (treated before 1975) Does Thyroid Supplementation Accelerate Tricyclic Antidepressant Response? A Review and Meta-Analysis of the Literature Altshuler, Bauer, Frye,et al. Am J Psychiatry 2001; 158:1617–1622 – 6 studies with 125 patients – 20-25 ug T3 Thyroid hormone in depression • Supraphysiologic Doses? • Thyroxine (mean 368 ug/day for 1 year [250-500]) Effects of supraphysiological thyroxine administration in healthy controls and patients with depressive disorders Michael Bauer, al. Journal of Affective Disorders 68 (2002) 285– 294 – fewer side-effects in depressed patients – improved subjective response Thyroid hormone in depression Hypothyroid & Depression Adding T3 to T4 in depressed patients • Does a Combination Regimen of Thyroxine (T4) and Triiodothyronine Improve Depressive Symptoms Better Than T4 Alone in Patients with Hypothyroidism? Results of a Double-Blind, Randomized, Controlled Trial • • A. M. SAWKA, H. C. GERSTEIN, M. J. MARRIOTT, G. M. MACQUEEN, AND R. T. JOFFE (JCEM 88: 4551–4555, 2003) Substituting T3 (12.5 ug, twice daily) for 50% of the T4 replacement dose did not improve self-assessed mood or well-being over 15 wk to a greater extent than continuing the pre-study dose of T4 and adding a placebo. Hypothyroid & Depression Summary • Thyroid hormone probably useful to augment a poor response to standard treatment • • • Best dose and length of treatment? Whether T3 or T4 is best still up in the air No evidence for substituting T3 for T4 in hypothyroid patients with depressive symptoms Wilson’s Syndrome Adding T3 to T4 in hypothyroid patients Combined Thyroxine/Liothyronine Treatment Does Not Improve Well-Being, Quality of Life, or Cognitive Function Compared to Thyroxine Alone: A Randomized Controlled Trial in Patients with Primary Hypothyroidism • JOHN P. WALSH, LAUREN SHIELS, EE MUN LIM, CHOTOO I. BHAGAT, LYNLEY C. WARD, BRONWYN G. A. STUCKEY, SATVINDER S. DHALIWAL, GERARD T. CHEW, MINOTI C. BHAGAT, AND ANDREA J. CUSSONS (JCEM 88: 4553–4550, 2003) Combined T4/T3 treatment does not improve wellbeing, cognitive function, or quality of life compared with T4 alone.