Transcript Endocrine Rounds

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
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TRH stimulation
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Blunted response in 25-30%
Exaggerated response in 10%
TRH levels in CSF increased
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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
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antidepressants increase deiodinases in rat brain
increase T3 levels in brain
Mood stabilizing agents
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Lithium, carbamazepine, valproic acid
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lower thyroid levels
Thyroid hormone in depression
Augmentation agents?
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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?
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T3 better than T4?
Joffe RT and Singer 1990 Psychiatry Research
53% response rate with T3 vs 19% with T4
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T4 in larger doses as effective as T3?
Bauer et al 1998, Neuropsychopharmacology
Rudas et al 1999, Biol Psychiatry
Thyroid hormone in depression
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Accelerate Tricyclic Response?
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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?
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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
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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
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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
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Thyroid hormone probably useful to augment a
poor response to standard treatment
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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
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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.