Keeping up with the clinical advances: depression

Ragguett, Renee-Marie; Tamura, Jocelyn K.; McIntyre, Roger S.

doi:10.1017/s1092852919001159

Cited by 27Treatment of Major DepressionTryptophan and brain disordersElectroconvulsive Therapy Studies

Keeping up with the clinical advances: depression

Ragguett, Renee-Marie, Tamura, Jocelyn K., McIntyre, Roger S.·2019·CNS Spectrums

DOI 10.1017/s1092852919001159

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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.

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GABAergic agents such as zuranolone, opioid receptor modulators, orexin antagonists, voltage-gated ion channel modulators, antiinflammatories, and agents targeting cellular metabolic processes are under investigation in treatment-resistant depression.
“Additionally, GABAergic agents (e.g., zuranolone), opioid receptor modulators, orexin antagonists, voltage- gated ion channels modulators, antiinflammatories, as well as agents targeting cellular metabolic processes are also under investigation in TRD 290 .”
From Treatment‐resistant depression: definition, prevalence, detection, management, and investigational interventions (2023) · cites this paper as [290]

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Authors: Ragguett, R.-M., Tamura, J. K., & McIntyre, R. S.
Affiliations: University Health Network (CA)
Corresponding author: McIntyre, Roger S.
ORCID: Ragguett, Renee-Marie
Tamura, Jocelyn K.
McIntyre, Roger S.
Venue: CNS Spectrums
Publisher: Cambridge University Press (CUP)
Published: 2019-06-28
Volume: 24
Issue: S1
Pages: 25-37
ISSN: 1092-8529 (ISSN-L)
2165-6509
DOI: 10.1017/s1092852919001159
OpenAlex: W2955038019
Cited by: 27
References: 74
Citations by year: 2025: 2 · 2024: 2 · 2023: 3 · 2022: 6 · 2021: 6 · 2020: 7 · 2019: 1
FWCI: 0.64
Type: journal article
Language: en
Open access: closed
Licence: www.cambridge.org/core/terms (unspecified)
Locations: CNS Spectrums (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
Keywords: major depressive disorder, treatment-resistant depression, rapid-acting antidepressants, ketamine, esketamine, brexanolone, minocycline, buprenorphine, samidorphan, glutamatergic system, GABAergic system, opioid system, monoamine hypothesis, antidepressant drug development
MeSH terms: Animals, Antidepressive Agents, Major Depressive Disorder, Depressive Disorder, Major, Humans, Molecular Targeted Therapy, Depressive Disorder, Treatment-Resistant

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