Depression (Study) • Holtorf Medical Group
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Depression (Study)

Many depressed and bipolar patients have undiagnosed thyroid  dysfunction as the underlying cause or major contributor to their  depression that is not detected by standard thyroid tests (23-38). The  dysfunction present with these conditions includes down regulation of D1  (reduced T4 to T3 conversion) and reduced uptake of T4 into the cell,  resulting in increased serum T4 levels with low intracellular T3 levels  (24-26,30,31,35,39-45) and upregulated D3, resulting in elevated reverse  T3 (23,24,30,31), which blocks thyroid effect (147,184-194) and is an  indicator of reduced transport of T4 into the cell (183,193).  Additionally, studies show that depressed patients have reduced T4  transport across the blood brain barrier due to a defective transport  protein, transthyretin, resulting in significantly reduced thyroid  levels in the brains of depressed patients despite “normal” serum levels  and standard thyroid tests (23,39,40) as well as a reduced TSH response  to TRH (28-31,43-50).

It is not surprising that  T4 and T4/T3 combinations may have some  benefit in depression; but due to the suppressed T4 to T3 conversion  from suppressed D1(24-26,30) and reduced uptake of T4 into the cell and  brain (25,31,39,40), timed-released T3 is significantly more beneficial  than T4 or T4/T3 combination supplementation (25,41,202,225-227).

In the International Journal of Neruopsychopharmacology,  Posternak M et al. published a double blind placebo control trial of 50  patients with normal thyroid function as defined by a normal TSH (1.5  +/- 0.8). The patients were randomized to receive 25 mcg of T3 or  placebo in addition to antidepressant therapy (221). The study found  almost a 2-fold increase in response rate with T3 and a 4.5 times  greater likelihood of experiencing a positive response at any point over  a six-week period with the addition of T3. Side effects were higher in  placebo group on 10/11 criteria including a significant increase in  nervousness with the placebo group.

Kelly T et al. investigated the effectiveness of T3 for the treatment  of biopolar disorder in who patients had failed to adequately respond  to an average of 14 medications used to treat their bipolar disorder.  The average dose of T3 used was 90.4 mcg (range 13 mcg-188 mcg). The  medication was found to be well tolerated and 84% experienced  significant improvement and 33% had a full remission. Again, this is in  patients who had not previously responded to numerous medications. One  patient who was switched to T4 for cost reasons experienced a return of  symptoms, which resolved with the reintroduction of T3. The authors  concluded, “Augmentation with supraphysiologic doses of T3 should be  considered in cases of treatment resistant bipolar depression… (227).”  The authors thanked several doctors who encouraged them to go beyond the  traditional 50 mcg of T3 because it has helped so many of their  patients.

With over 4000 patients, The Star*D Report is the largest trial  comparing antidepressant effectiveness for depression. It found that 66%  of patients fail to respond to antidepressants or have side-effects  severe enough to discontinue use. Of those who do respond, over half  will relapse within one year (228). The trial found that T3 was  effective even when other medications — such as citalopram (Celexa),  bupropion (Wellbutrin), sertraline (Zolft), venlafaxine (Effexor), or  cognitive therapy – were not. It was shown to be 50% more effective,  even with the less than optimal dose of 50 mcg, under direct comparison  with significantly less side effects than commonly used therapeutic  approaches with standard antidepressants. The authors included a case  study to exemplify the effectiveness of T3, especially when other  medications are not:

    “Ms. “B,” a 44-year-old divorced white woman, became depressed after  losing her job as a secretary in a law firm. She initially sought  treatment from her primary care physician and then entered the STAR*D  study. Ms. B met criteria for major depressive disorder and generalized  anxiety disorder. Her baseline QIDS-SR score was 16. After 12 weeks on  citalopram, her QIDS-SR score was 10 [minimal response]. She was then  randomly assigned to augmentation with buspirone; she soon experienced  gastrointestinal distress, and she stopped taking buspirone after 6  weeks. She elected to try one more augmentation agent and was randomly  assigned to T3 augmentation. When she started T3 augmentation, her  QIDS-SR score was 12.  After 4 weeks, she felt that her mood and energy  had lifted substantially. She felt better able to make decisions,  organize, and prioritize and felt that she was able and ready to look  for another job. “I felt as if my brain suddenly had oxygen,” she said,  “and everything became clearer.” After 12 weeks, Ms. B felt back to  normal, and her QIDS-SR score was 0 [complete resolution of symptoms]  (228).”

With an understanding of thyroid physiology and associated  dysfunction that is present in depressed patients, it is clear that  timed-released T3 supplementation should be considered in all depressed  and bipolar patients despite “normal” serum thyroid levels.  Additionally, straight T4 should be considered inappropriate and  suboptimal therapy for replacement in such patients.