Innovations In Clinical Neuroscience

MAR-APR 2017

A peer-reviewed, evidence-based journal for clinicians in the field of neuroscience

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Innovations in CLINICAL NEUROSCIENCE [ V O L U M E 1 4 , N U M B E R 3 – 4 , M A R C H – A P R I L 2 0 1 7 ] 28 have focused on the use of T3 in combination with TCAs and have yielded mixed results. Larger studies of longer duration are needed to evaluate T3's efficacy with newer and other classes of antidepressants. Despite these limitations, T3 augmentation appears to be a safe and effective alternative treatment for euthyroid patients with unipolar depression who receive appropriate baseline and follow-up safety monitoring. REFERENCES 1. Kessler RC, Chiu WT, Demler O, et al. Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005;62(6):617–627. 2. Harvard Medical School site. National Comorbidity Survey-Replication (NCS- R). http://www.hcp.med.harvard.edu/ ncs/. Accessed 31 March 2016. 3. McIntyre RS, Filteau MJ, Martin L, et al. Treatment-resistant depression: definitions, review of the evidence, and algorithmic approach. J Affect Disord. 2014;156:1–7. 4. American Psychiatric Association site. Practice Guideline for Treatment of Patients with Major Depressive Disorder, Third Edition. http://psychiatryonline.org/guidelines November 2010. Accessed 1 June 2016. 5. Lam RW, Kennedy SH, Grigoriadis S, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) clinical guidelines for the management of major depressive disorder in adults. III: pharmacotherapy. J Affect Disord. 2009;117(Suppl 1):S26–S43. 6. Segerson TP, Kauer J, Wolfe HC, et al. Thyroid hormone regulates TRH biosynthesis in the paraventricular nucleus of the rat hypothalamus. Science. 1987 2;238(4823):78–80. 7. Ceccatelli S, Giardino L, Calzá L. Response of hypothalamic peptide mRNAs to thyroidectomy. Neuroendocrinology. 1992;56(5):694–703. 8. Giardino L, Ceccatelli S, Zanni M, et al. Regulation of VIP mRNA expression by thyroid hormone in different brain areas of adult rat. Brain Res Mol Brain Res. 1994;27(1):87–94. 9. Lifschytz T, Segman R, Shalom G, et al. Basic mechanisms of augmentation of antidepressant effects with thyroid hormone. Curr Drug Targets. 2006;7(2):203–210. 10. Newman ME, Agid O, Gur E, Lerer B. Pharmacological mechanisms of T3 augmentation of antidepressant action. Int J Neuropsychopharmacol. 2000;3(2):187–191. 11. Gur E, Lerer B, Newman ME. Chronic clomipramine and triiodothyronine increase serotonin levels in rat frontal cortex in vivo: relationship to serotonin autoreceptor activity. J Pharmacol Exp Ther. 1999;288(1):81–87. 12. Banki CM. Cerebrospinal fluid amine metabolites after combined amitriptyline-triiodothyronine treatment of depressed women. Eur J Clin Pharmacol. 1977;11:311–315. 13. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960;23:56–62. 14. Altshuler LL, Bauer M, Frye MA, et al. Does thyroid supplementation accelerate tricyclic antidepressant response? a review and metaanalysis of the literature. Am J Psychiatry. 2001;158:1617–1622. 15. Coppen A, Whybrow P, Noguera R, et al. The comparative antidepressant value of L-tryptophan and imipramine with and without attempted potentiation by liothyronine. Arch Gen Psychiatry. 1972;26:234–241. 16. Feighner JP, King LJ, Schuckit MA, et al. Hormonal potentiation of imipramine and ECT in primary depression. Am J Psychiatry. 1972;128:1230–1238. 17. Prange AJ Jr,Wilson IC, Rabon AM, Lipton MA. Enhancement of imipramine antidepressant activity by thyroid hormone. Am J Psychiatry. 1969;126(4):457–469. 18. Wheatley D. Potentiation of amitriptyline by thyroid hormone. Arch Gen Psychiatry. 1972;26(3):229–233. 19. Wilson IC, Prange AJ, McClane TK, et al. Thyroid-hormone enhancement of imipramine in nonretarded depressions. N Engl J Med. 1970;282:1063–1067. 20. Wilson IC, Prange AJ Jr, Lara PP. L- triiodothyronine alone and with imipramine in the treatment of depressed women. In: Prange AJ Jr (ed). The Thyroid Axis, Drugs, and Behavior. New York, Raven Press; 1974:49–62. 21. Earle BV. Thyroid hormone and tricyclic antidepressants in resistant depressions. Am J Psychiatry. 1970;126:1667–1669. 22. Ogura C, Okuma T, Uchida Y, et al. Combined thyroid (triiodothyronine)- tricyclic antidepressive treatment in depressive states. Folia Psychiatr Neurol Jpn. 1974;28:179–186. 23. Tsutsui S, Yamazaki Y, Namba T, Tsushima M. Combined therapy of T3 and antidepressants in depression. J Int Med Res. 1979;7:138–146. 24. Schwarcz G, Halaris A, Baxter L, et al. Normal thyroid function in desipramine nonresponders converted to responders by the addition of L- triiodothyronine. Am J Psychiatry. 1984;141:1614–1616. 25. Nakamura T, Nomura J. Comparison of thyroid function between responders and nonresponders to thyroid hormone supplementation in TABLE 3. Guidelines for using T3 (adapted from Rosenthal 2011) 40 • Check TSH, free T3, and free T4 levels prior to initiating treatment. • If TSH, free T3, and free T4 levels are abnormal, recheck labs to rule out laboratory error or transient stressors as causes. • Start with 25mcg daily and titrate to 50mcg daily after at least one week (starting with 12.5mcg may be appropriate in older patients or those with medication sensitivities). • Recheck thyroid indices at 3 months and then every 6 months, or at minimum annually. • Goal TSH level is at least at the lower limit of the normal range or below in the absence of hyperthyroid symptoms. • Free T3 level can be maintained at the upper limit of the normal range based on the severity of depressive symptoms and response to T3. • Monitor bone density with densitometry every 2 years in postmenopausal women. • Refer for evaluation of osteoporosis if bone density is declining.

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