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Synthroid Mental Health and Mood Impact: What the Evidence Actually Shows

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At a glance

  • What it is / Synthetic T4 replacement for hypothyroidism [1]
  • Approved uses / Hypothyroidism and TSH suppression in thyroid cancer [1]
  • Cognitive warning / Under- and over-treatment may negatively affect cognitive function [1]
  • Overdose mood effects / Anxiety, nervousness, irritability, emotional lability, insomnia [1]
  • Guideline view / ATA 2014 reviewed why some patients feel unwell on T4 alone [2]
  • Genetic signal / DIO2 CC genotype 16% in a 552-patient analysis; greater GHQ improvement on T4 plus T3 [3]
  • Monitoring / Periodic TSH and/or T4 plus clinical status [1]

Does levothyroxine treat depression or anxiety?

No. The approved uses are hypothyroidism and, with surgery and radioiodine, TSH suppression in thyrotropin-dependent well-differentiated thyroid cancer [1]. Depression is not an approved indication [1]. The label's central nervous system adverse reactions from too much hormone include anxiety, nervousness, irritability, emotional lability and insomnia [1].

What the label says about mood and thinking

Levothyroxine has a narrow therapeutic index. The label warns that both overtreatment and undertreatment may have negative effects on cognitive function [1]. The label says adequacy of therapy is judged with periodic TSH and/or T4 plus clinical status, and the peak effect of a given dose may take 4 to 6 weeks [1].

The DIO2 finding

One analysis of 552 people taking T4 in the Weston Area T4/T3 Study looked at baseline psychological well-being and at response to T4 plus T3 compared with T4 alone [3]. The DIO2 rs225014 CC genotype was present in 16%. It was associated with worse baseline GHQ-12 scores on T4 (14.1 vs 12.8 for TT, P=0.03) and greater improvement on T4 plus T3 than on T4 alone: 2.3 GHQ points at 3 months and 1.4 at 12 months (P=0.03 for repeated measures ANOVA). The genotype did not affect circulating thyroid hormone levels, and the authors said the results require replication [3].

What the ATA guideline adds

The 2014 American Thyroid Association task force reviewed why some patients feel unwell on levothyroxine monotherapy, treatment alternatives, and relevant knowledge gaps [2].

Frequently asked questions

Does levothyroxine help with depression?
Levothyroxine is approved for hypothyroidism and for TSH suppression in thyroid cancer, not for depression [1]. The label's mental-health warnings concern cognitive effects of under- or over-treatment and hyperthyroid symptoms from overdosage, such as anxiety and insomnia [1]. The 2014 ATA guideline notes that some patients feel unwell on levothyroxine monotherapy and reviews alternatives [2].
Can levothyroxine cause anxiety or insomnia?
Yes, as effects of too much hormone. The label lists anxiety, nervousness, irritability, emotional lability and insomnia among the central nervous system adverse reactions of hyperthyroidism due to therapeutic overdosage [1]. It also lists palpitations, tachycardia and tremor [1].
What does the label say about memory and thinking?
The label warns that levothyroxine has a narrow therapeutic index and that both overtreatment and undertreatment may have negative effects on cognitive function [1].
Does adding T3 improve mood on levothyroxine?
Not as a general finding. One analysis of 552 patients taking T4 found that those with the DIO2 rs225014 CC genotype, present in 16%, had worse baseline GHQ-12 scores and a greater improvement on T4 plus T3 than on T4 alone [3]. The authors said the results require replication, and the polymorphism did not change circulating thyroid hormone levels [3].

References

  1. U.S. National Library of Medicine, DailyMed. Levothyroxine sodium prescribing information. Levothyroxine sodium label
  2. Jonklaas J, Bianco AC, Bauer AJ, Burman KD, Cappola AR, Celi FS, et al. Guidelines for the treatment of hypothyroidism: prepared by the american thyroid association task force on thyroid hormone replacement. Thyroid. 2014;24(12):1670-751. Guidelines for the treatment of hypothyroidism: prepared by the american thyroid association task force on thyroid hormone replacement
  3. Panicker V, Saravanan P, Vaidya B, Evans J, Hattersley AT, Frayling TM, et al. Common variation in the DIO2 gene predicts baseline psychological well-being and response to combination thyroxine plus triiodothyronine therapy in hypothyroid patients. J Clin Endocrinol Metab. 2009;94(5):1623-9. Common variation in the DIO2 gene predicts baseline psychological well-being and response to combination thyroxine plus triiodothyronine therapy in hypothyroid patients
  4. Singh N, Singh PN, Hershman JM. Effect of calcium carbonate on the absorption of levothyroxine. JAMA. 2000;283(21):2822-5. Effect of calcium carbonate on the absorption of levothyroxine
  5. Campbell NR, Hasinoff BB, Stalts H, Rao B, Wong NC. Ferrous sulfate reduces thyroxine efficacy in patients with hypothyroidism. Ann Intern Med. 1992;117(12):1010-3. Ferrous sulfate reduces thyroxine efficacy in patients with hypothyroidism
Evidence overview for levothyroxine: Synthroid Mental Health and Mood Impact: What the Evidence Actually Shows