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Review
. 2020 Jan 21:16:221-234.
doi: 10.2147/NDT.S198774. eCollection 2020.

Management of Treatment-Resistant Depression: Challenges and Strategies

Daphne Voineskos  1   2 , Zafiris J Daskalakis  1   2 , Daniel M Blumberger  1   2
Affiliations
Review

Management of Treatment-Resistant Depression: Challenges and Strategies

Daphne Voineskos et al. Neuropsychiatr Dis Treat. .

Abstract

Treatment-resistant depression (TRD) is a subset of Major Depressive Disorder which does not respond to traditional and first-line therapeutic options. There are several definitions and staging models of TRD and a consensus for each has not yet been established. However, in common for each model is the inadequate response to at least 2 trials of antidepressant pharmacotherapy. In this review, a comprehensive analysis of existing literature regarding the challenges and management of TRD has been compiled. A PubMed search was performed to assemble meta-analyses, trials and reviews on the topic of TRD. First, we address the confounds in the definitions and staging models of TRD, and subsequently the difficulties inherent in assessing the illness. Pharmacological augmentation strategies including lithium, triiodothyronine and second-generation antipsychotics are reviewed, as is switching of antidepressant class. Somatic therapies, including several modalities of brain stimulation (electroconvulsive therapy, repetitive transcranial magnetic stimulation, magnetic seizure therapy and deep brain stimulation) are detailed, psychotherapeutic strategies and subsequently novel therapeutics including ketamine, psilocybin, anti-inflammatories and new directions are reviewed in this manuscript. Our review of the evidence suggests that further large-scale work is necessary to understand the appropriate treatment pathways for TRD and to prescribe effective therapeutic options for patients suffering from TRD.

Keywords: brain stimulation; major depressive disorder; novel therapies; pharmacotherapy; psychotherapy; treatment resistant depression.

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Conflict of interest statement

Dr. Zafiris J Daskalakis reports grants from Magventure Inc. and grants from Brainsway Inc., during the conduct of the study. The authors report no other conflicts of interest in this work.

References

    1. Aan Het Rot M, Collins KA, Murrough JW, et al. Safety and efficacy of repeated-dose intravenous ketamine for treatment-resistant depression. Biol Psychiatry. 2010;67(2):139–145. doi: 10.1016/j.biopsych.2009.08.038 - DOI - PubMed
    1. Abraham G, Milev R, Stuart Lawson J. T3 augmentation of SSRI resistant depression. J Affect Disord. 2006;91(2–3):211–215. doi: 10.1016/j.jad.2006.01.013 - DOI - PubMed
    1. APA. Practice guideline for the treatment of patients with major depressive disorder. Available from: https://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/.... Accessed January8, 2020.
    1. APA Committee on Electroconvulsive Therapy. The Practice of Electroconvulsive Therapy: Recommendations for Treatment, Training and Privileging: A Task Force Report of the American Psychiatric Association; 2001; APA.
    1. Aronson R, Offman HJ, Joffe RT, Naylor CD. Triiodothyronine augmentation in the treatment of refractory depression. A meta-analysis. Arch Gen Psychiatry. 1996;53(9):842–848. doi: 10.1001/archpsyc.1996.01830090090013 - DOI - PubMed