From the Research
Racial disparities in ketamine metabolism exist, and clinicians should consider starting with lower initial doses in Black and Asian individuals due to genetic variations in cytochrome P450 enzymes, particularly CYP2B6 and CYP3A4, as evidenced by a systematic review of pharmacogenomics of ketamine 1.
Key Considerations
- Genetic variations in CYP2B6 and CYP3A4 enzymes affect ketamine metabolism, leading to slower metabolism in Black and Asian individuals compared to white individuals 2, 3.
- Slower metabolism can result in higher blood concentrations and potentially stronger or longer-lasting effects at standard doses.
- Clinicians should consider starting with lower initial doses (perhaps 0.3-0.4 mg/kg instead of 0.5 mg/kg for intravenous administration) in these populations and titrate carefully based on response.
- For maintenance ketamine therapy, dose adjustments of 10-20% lower may be appropriate in some racial groups.
Metabolic Differences
- Polymorphisms in metabolic enzymes, such as CYP2B6 and CYP3A4, affect how quickly the body converts ketamine to its metabolites, including norketamine 2, 3.
- Cultural factors affecting pain perception and reporting may compound these biological differences.
Monitoring and Titration
- Careful monitoring for side effects like dissociation, sedation, and cardiovascular changes is essential regardless of racial background.
- Awareness of these metabolic differences can help providers deliver more personalized and effective ketamine treatment across diverse populations.
Pharmacogenomics
- A systematic review of pharmacogenomics of ketamine identified predictors of antidepressant response and adverse effects, including Val66Met (rs6265) brain derived neurotrophic factor (BDNF; Met allele) and CYP2B6*6 (e.g., CYB2B6 metabolizer) 1.
- Further research is needed to better determine genetic variants of greatest importance and the clinical validity of pharmacogenomics to help guide ketamine treatment planning.