Pharmacogenomics of ketamine: A systematic review

This review (2021) explores the pharmacogenomic predictors of ketamine’s clinical benefits and adverse effects. The review identified three predictors; 1) brain derived neurotrophic growth factor (BDNF) was associated with reduced antidepressant and anti-suicidal effects, 2) CYB2B6 was associated with more severe dissociative effects and 3) NET was associated with greater cardiovascular complications. Limitations include small sample sizes and heterogeneity of study design.

Abstract

“Ketamine is a dissociative anesthetic used worldwide for anesthesia, pain management, treatment resistant depression (TRD) and suicidality. Predictors of antidepressant response and adverse effects to ketamine remain poorly understood due to contradictory results. The objective of the systematic review herein is to identify and evaluate the extant literature assessing pharmacogenomic predictors of ketamine clinical benefits and adverse effects. Electronic databases were searched from inception to July 2021 to identify relevant articles. Twelve articles involving 1,219 participants with TRD, 75 who underwent elective surgeries and received ketamine as an anesthetic, 49 with pain, and 68 healthy participants met the inclusion criteria and enrolled to this review. While identified articles reported mixed results, three predictors emerged: 1) Val66Met (rs6265) brain derived neurotrophic factor (BDNF; Met allele) was associated with reduced antidepressant and anti-suicidal effects, 2) CYP2B6*6 (e.g., CYB2B6 metabolizer) was associated with more severe dissociative effects and 3) NET allelic (rs28386840) variant were associated with greater cardiovascular complications (e.g., moderate to severe treatment emergent hypertension). Several important limitations were identified, most notably the small sample sizes and heterogeneity of study design and results. Taken together, preliminary evidence suggests the potential for pharmacogenomic testing to inform clinical practices; however, further research is needed to better determine genetic variants of greatest importance and the clinical validity of pharmacogenomics to help guide ketamine treatment planning.”

Authors: Shaklia Meshkat, Nelson B. Rodrigues, Joshua D. Di Vincenzo, Felicia Ceban, Saja Jaberi, Roger S. McIntyre, Leanna M. W. Lui & Joshua D. Rosenblat

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Pharmacogenomics of ketamine: A systematic review

https://doi.org/10.1016/j.jpsychires.2021.11.036

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Published in
Journal of Psychiatric Research
November 30, 2021
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Study details

Compounds studied
Ketamine

Participants
0 Humans

Institutes

Institutes associated with this publication

University Health Network Toronto
University Health Network is a public research and teaching hospital network in Toronto. The Nikean Psychedelic Psychotherapy Research Centre was established in 2021.