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Management of Treatment-Resistant Depression: Challenges and Strategies

Authors Voineskos D, Daskalakis ZJ, Blumberger DM

Received 11 October 2019

Accepted for publication 7 January 2020

Published 21 January 2020 Volume 2020:16 Pages 221—234


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Roger Pinder

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

1Centre for Addiction and Mental Health, Toronto, Ontario, Canada; 2Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada

Correspondence: Daniel M Blumberger
Centre for Addiction and Mental Health, 1001 Queen Street West, Unit 4-1, Toronto, Ontario M6J1H4, Canada
Tel +1 416 535-8501
Fax +1 416 583-1358

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: treatment resistant depression, major depressive disorder, pharmacotherapy, psychotherapy, brain stimulation, novel therapies

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