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Thyroid Hormone Augmentation for Bipolar Disorder: A Systematic Review.

Ashok Seshadri1,2, Vishnu Sundaresh3, Larry J Prokop4

  • 1Department of Psychiatry & Psychology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.

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Thyroid hormone augmentation shows mixed results for bipolar disorder (BD). While some studies suggest benefits for depression and rapid cycling, high-quality evidence is lacking, warranting cautious use in treatment-resistant cases.

Keywords:
LT4T3bipolar depressionbipolar disorderslevothyroxineliothyroninerapid cyclingthyroid hormone

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Area of Science:

  • Endocrinology
  • Psychiatry
  • Pharmacology

Background:

  • Thyroid hormone (TH) augmentation is common in major depression but less so in bipolar disorder (BD).
  • Mechanisms of TH action in BD are unclear, but central TH deficit is hypothesized in rapid cycling.
  • Mood stabilizers are the primary treatment for BD.

Purpose of the Study:

  • To systematically review the evidence for thyroid hormone augmentation in bipolar disorder.
  • To synthesize findings from randomized controlled trials (RCTs), open-label trials, and observational studies.
  • To evaluate the efficacy and safety of levothyroxine (LT4) and triiodothyronine (T3) in BD.

Main Methods:

  • Systematic literature search of Ovid MEDLINE, Embase, PsycINFO, and Cochrane databases.
  • Inclusion of RCTs, open-label trials, and observational studies.
  • Synthesis of evidence for LT4 and T3 augmentation in BD, following PRISMA guidelines.

Main Results:

  • Open-label studies indicated potential benefits of high-dose LT4 for bipolar depression and rapid cycling.
  • An RCT of high-dose LT4 did not show significant benefits over placebo.
  • Another RCT found LT4 and T3 beneficial only in rapid-cycling bipolar women; meta-analysis was not feasible.
  • Thyroid hormone augmentation was generally well-tolerated with no significant thyrotoxicosis reported.

Conclusions:

  • Evidence for TH augmentation in BD is mixed, with a lack of high-quality studies.
  • The promise of supratherapeutic LT4 augmentation from open-label trials is not consistently replicated in RCTs.
  • Limited data exist for T3 augmentation.
  • TH augmentation, particularly supratherapeutic doses, should be reserved for highly treatment-resistant bipolar depression and rapid-cycling BD.