Key considerations in the pharmacological management of treatment-resistant depression

ABSTRACT

Introduction: Treatment-resistant depression (TRD) is a complex, multifactorial, and biologically heterogeneous disorder with debilitating outcomes. Understanding individual reasons why patients do not respond to treatment is necessary for improving clinical recommendations regarding medication regimens, augmentation strategies, and alternative treatments.

Areas covered: This manuscript reviews evidence-based treatment strategies for the clinical management of TRD. Current developments in the field and potential future recommendations for personalized treatment of TRD are also discussed.

Expert opinion: Treatment guidelines for TRD are limited by the heterogeneous nature of the disorder. Furthermore, current strategies reflect this heterogeneity by emphasizing disease characteristics as well as drug trial response or failure. Developing robust biomarkers that could one day be integrated into clinical practice has the potential to advance specific treatment targets and ultimately improve treatment and remission outcomes.

KEYWORDS:

• Augmentation
• biomarkers
• depression
• guidelines
• ketamine
• management
• treatment-resistant

Declaration of interest

Dr. Zarate is listed as a co-inventor on a patent for the use of ketamine in major depression and suicidal ideation; as a co-inventor on a patent for the use of (2R,6R)-hydroxynorketamine, (S)-dehydronorketamine, and other stereoisomeric dehydroxylated and hydroxylated metabolites of (R,S)-ketamine metabolites in the treatment of depression and neuropathic pain; and as a co-inventor on a patent application for the use of (2R,6R)-hydroxynorketamine and (2S,6S)-hydroxynorketamine in the treatment of depression, anxiety, anhedonia, suicidal ideation, and post-traumatic stress disorders. He has assigned his patent rights to the U.S. government but will share a percentage of any royalties that may be received by the government.

Additional information

Funding

Funding for this work was provided by the Intramural Research Program at the National Institute of Mental Health, National Institutes of Health (IRP-NIMH-NIH; ZIAMH002927). The work was completed as part of the authors’ official duties as Government employees. The views expressed do not necessarily reflect the views of the NIH, the Department of Health and Human Services, or the United States Government.