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 ] 24 ABSTRACT Objective: The objective of this review is to discuss triiodothyronine's (T3, liothyronine) mechanism of action, efficacy in enhancement and augmentation trials, and dosing and safety considerations for the treatment of depression. Method: A literature search of PubMed was performed using search terms depression, augmentation, antidepressant, and liothyronine. Only English-language studies of subjects with unipolar depression were included from the past 50 years. Results: Most studies have shown that liothyronine is an efficacious enhancement and augmentation strategy for depression in combination with antidepressants, primarily tricyclic antidepressants and selective serotonin reuptake inhibitors. Conclusion: With appropriate baseline and follow-up safety monitoring, liothyronine augmentation can be a safe and effective treatment for unipolar depression. Larger studies of longer duration assessing liothyronine efficacy with serotonin norepinephrine reuptake inhibitors and multimodal antidepressants are needed. INTRODUCTION Major depressive disorder (MDD) has a 12-month prevalence of 6.7 percent and a lifetime prevalence of 16.9 percent. 1,2 Treatment-resistant depression is defined as lack of response after trials of two or more antidepressants with different mechanisms of action for sufficient duration. 3 Such antidepressants include tricyclic antidepressants (TCA), selective serotonin reuptake inhibitors (SSRI), serotonin norepinephrine reuptake inhibitors (SNRI), monoamine oxidase inhibitors (MAOI), bupropion, mirtazapine, and trazodone. Current guidelines suggest augmentation of antidepressants for individuals with treatment-resistant unipolar depression. 4,5 There are several augmenting agents, one of which is the thyroid hormone triiodothyronine (T3 or liothyronine). This review discusses T3's mechanism of action, efficacy in enhancement and augmentation trials, and dosing and safety considerations. MECHANISM OF ACTION Thyroid hormone is postulated to exert antidepressant efficacy through multiple mechanisms. Depression is associated with neuronal death, so it follows that decreasing neuronal stress, atrophy, and death would be associated with an antidepressant effect. T3 has been shown to increase gene expression by increasing levels of thyrotropin- releasing hormone, corticotrophin by KATIE T.B. TOUMA, PharmD, BCPP, BCPS; ALLYSA M. ZOUCHA, PharmD, BCPP; and JONATHAN R. SCARFF, MD Drs. Blissit and Zoucha are with William Jennings Bryan Dorn VA Medical Center, Anderson Community Based Outpatient Clinic, Anderson, South Carolina, and Dr. Scarff is with William Jennings Bryan Dorn VA Medical Center, Spartanburg Community Based Outpatient Clinic Spartanburg, South Carolina. Innov Clin Neurosci. 2017;14(3–4):24–29 FUNDING: No funding was received for the preparation of this article. FINANCIAL DISCLOSURES: The authors have no conflicts of interest relevant to the content of this article. ADDRESS CORRESPONDENCE TO: Jonathan R. Scarff, MD, 279 North Grove Medical Park Drive, Spartanburg, SC 29303 Phone: (864) 582-7025; Fax: (864) 583-5715 email: Jonathan.Scarff2@va.gov KEY WORDS: Triiodothyronine, liothyronine, T3, treatment-resistant depression, augmentation, enhancement R E V I E W Liothyronine for Depression: A Review and Guidance for Safety Monitoring

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