What is the role of genetic testing in guiding the selection of antidepressant (Anti-Depressant) medications for patients with major depressive disorder?

From the Guidelines

Genetic testing for depression medications can be helpful but is not yet a standard first-line approach, and I recommend considering pharmacogenomic testing primarily if you've failed multiple antidepressant trials or experienced severe side effects. The most recent and highest quality study on this topic is from 2016, which provides a template for psychiatric precision medicine 1. This study highlights the importance of genetic variation in individualizing treatment selection for depression, particularly with regards to cytochrome P450 2D6 (CYP2D6) and cytochrome P450 2C19 (CYP2C19) genetic testing.

Some key points to consider when thinking about genetic testing for depression medications include:

• Tests like GeneSight or Genesight examine genes such as CYP2D6, CYP2C19, and CYP3A4 that affect how medications like SSRIs (fluoxetine, sertraline, escitalopram) and SNRIs (venlafaxine, duloxetine) are metabolized in your body.
• If you're interested in testing, discuss it with your psychiatrist or primary care provider, as insurance coverage varies and out-of-pocket costs range from $300-2000.
• The testing process involves a simple cheek swab or saliva sample, with results typically available within 1-2 weeks.
• While these tests can identify if you're a poor, normal, or ultra-rapid metabolizer of certain medications, they don't predict which antidepressant will be most effective for your specific depression symptoms.

It's also important to note that the science behind this testing is still evolving, and genes influence medication metabolism, but depression response depends on many factors beyond genetics, including environment, lifestyle, and other biological factors, as highlighted in earlier studies from 2007 1. For most patients, the standard approach of medication trials based on symptom profile and side effect concerns remains appropriate.

From the Research

Genetic Testing for Depression Drugs

• Genetic testing for CYP2D6 and CYP2C19 can help guide the treatment of depressive disorders by identifying individuals who may be more prone to non-response and side-effects of psychotropic medications 2.
• Studies have shown that pharmacogenomic tests, including CYP2D6 and CYP2C19 genomic variants, can improve treatment outcomes in major depression, with increased odds of improvement, response, and remission compared to treatment as usual 3.
• The clinical impact of CYP2C19 and CYP2D6 gene variants on antidepressant treatment in people with depression has been investigated, with results suggesting that poor metabolizer (PM) phenotype statuses are associated with increased risks of treatment switching, psychiatric emergency department contacts, and suicide attempt/self-harm in children, adolescents, and young adults 4.
• Estimating the potential impact of CYP2C19 and CYP2D6 genetic testing on protocol-based care for depression in Canada and the United States suggests that up to one-third of the population being treated for depression could benefit from the addition of genetic testing 5.
• A systematic review of pharmacogenetic tests to guide drug treatment in depression found that variants in CYP2D6 and CYP2C19 have adequate support for clinical application, but that further research is needed to assess the exact benefit of pharmacogenetics in clinical practice 6.

Benefits of Genetic Testing

• Genetic testing can help identify individuals who are more likely to experience side effects or non-response to certain medications, allowing for more personalized treatment plans 2.
• Pharmacogenomic tests can improve treatment outcomes in major depression, with increased odds of improvement, response, and remission compared to treatment as usual 3.
• Genetic testing can help reduce the risk of treatment switching, psychiatric emergency department contacts, and suicide attempt/self-harm in children, adolescents, and young adults 4.

Limitations and Future Directions

• Further research is needed to assess the exact benefit of pharmacogenetics in clinical practice and to develop best practices for clinical evidence development and health economic assessment 6.
• The clinical application of pharmacogenetic tests is limited by the lack of standardization and regulation of genetic testing kits and the need for more randomized controlled trials to establish the efficacy of these tests 6.
• The potential benefits of genetic testing for depression drugs need to be weighed against the costs and potential risks of testing, and more research is needed to determine the cost-effectiveness of genetic testing in this context 5.