From the Guidelines
GeneSight testing does not have sufficient evidence to support its use as a guide for selecting antidepressants, according to the most recent and highest quality study. The 2022 U.S. Department of Veterans Affairs and U.S. Department of Defense clinical practice guideline found that the quality of evidence for pharmacogenomic testing, including GeneSight, was very low due to small sample sizes and concerns about potential bias because the studies were commercially funded 1. Although there is extensive interest in developing approaches to better match patients to treatments, the findings were mixed in terms of outcomes, and the work group determined that it was not enough to make a recommendation.
Some studies suggest that pharmacogenetic matching may have some benefit, but the evidence is not strong enough to support its use in clinical practice 1. The test analyzes genetic variations that may affect how patients respond to and metabolize psychiatric medications, potentially helping clinicians select more effective antidepressants with fewer side effects. However, the current evidence does not support its use as a standard tool for guiding depression treatment.
Key points to consider when evaluating the use of GeneSight testing include:
- The quality of evidence is very low due to small sample sizes and potential bias
- The findings are mixed in terms of outcomes
- The test may be relevant for only about 15% to 20% of participants being considered for medication
- The cost of the test is approximately $300-$2,000, though insurance may cover it partially
- GeneSight testing should not replace comprehensive clinical assessment and patient history in medication selection.
From the Research
GeneSight Testing Benefits
- The GeneSight test has been shown to improve depression outcomes in patients with major depressive disorder 2, 3.
- Studies have demonstrated that patients who received GeneSight-guided treatment had improved response to depression treatment, greater improvements in measures of depression, and greater patient and clinician satisfaction compared to those who received treatment as usual 2, 3, 4.
- The use of GeneSight has been associated with increased likelihood of response and remission in patients with treatment-resistant depression, and identifies patients with severe gene-drug interactions who have the greatest improvement in depressive symptoms when switched to genetically suitable medication regimens 3.
- However, the quality of evidence for the benefits of GeneSight testing is generally considered low to very low due to limitations in the studies, such as small sample sizes and limited generalizability to other populations 4.
Mechanisms and Interactions
- GeneSight testing takes into account the patient's genetic profile, including variants in genes such as CYP2D6, CYP2C19, and HTR2A, to guide medication selection 2, 3.
- The test provides a report that categorizes medications into green, yellow, or red "bins" based on their potential interaction with the patient's genetic profile 3.
- Medications that are contraindicated based on the patient's genotype (i.e., "red bin" medications) may be associated with reduced efficacy or increased risk of adverse effects 3, 5.
- GeneSight testing may be particularly useful in patients who are taking medications that are metabolized by CYP2D6 or other enzymes that are subject to genetic variation 5.