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Keeping up with the clinical advances: depression

Published online by Cambridge University Press:  28 June 2019

Renee-Marie Ragguett ,
Jocelyn K. Tamura  and
Roger S. McIntyre Open the ORCID record for Roger S. McIntyre [Opens in a new window]
Renee-Marie Ragguett
Affiliation:
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Canada
Jocelyn K. Tamura
Affiliation:
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Canada
Roger S. McIntyre*
Affiliation:
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Canada Department of Psychiatry, University of Toronto, Toronto, Canada Department of Pharmacology, University of Toronto, Toronto, Canada
*
*Address correspondence to: Roger S. McIntyre, Mood Disorders Psychopharmacology Unit, University Health Network, 399 Bathurst Street, Toronto, Ontario, M5T 2S8, Canada. (Email: roger.mcintyre@uhn.ca)
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Abstract

Major depressive disorder (MDD) is a prevalent and heterogeneous disorder. Although there are many treatment options for MDD, patients with treatment-resistant depression (TRD) remain prevalent, wherein delayed time to response results in inferior chances of achieving remission. Recently, therapeutics have been developed that depart from the traditional monoamine hypothesis of depression and focus instead on the glutamatergic, GABAergic, opioidergic, and inflammatory systems. The literature suggests that the foregoing systems are implicated in the pathophysiology of MDD and preclinical trials have informed the development of pharmaceuticals using these systems as therapeutic targets. Pharmaceuticals that target the glutamatergic system include ketamine, esketamine, and rapastinel; brexanolone and SAGE-217 target the GABAergic system; minocycline targets the inflammatory system; and the combinatory agent buprenorphine + samidorphan targets the opioidergic system. The aforementioned agents have shown efficacy in treating MDD in clinical trials. Of particular clinical relevance are those agents targeting the glutamatergic and GABAergic systems as they exhibit rapid response relative to conventional antidepressants. Rapid response pharmaceuticals have the potential to transform the treatment of MDD, demonstrating reduction in depressive symptoms within 24 hours, as opposed to weeks noted with conventional antidepressants. Novel therapeutics have the potential to improve both patient mood symptomatology and economical productivity, reducing the debased human capital costs associated with MDD. Furthermore, a selection of therapeutic targets provides diverse treatment options which may be beneficial to the patient considering the heterogeneity of MDD.

Keywords

Major depressive disorderglutamateketamineesketaminerapastinelGABAbrexanoloneSAGE-217inflammationminocyclineopioidsbuprenorphine + samidorphan
Type
CME Review Article
Information
CNS Spectrums , Volume 24 , Issue S1: CME SUPPLEMENT , August 2019 , pp. 25 - 37
Copyright
© Cambridge University Press 2019 

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Footnotes

This activity is supported by an unrestricted educational grant from Sage Therapeutics.

An addendum has been issued for this article, please see DOI: https://doi.org/10.1017/S1092852919001433.

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