Testing for cytochrome P450 polymorphisms in adults with nonpsychotic depression treated with selective serotonin reuptake inhibitors
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Patients metabolize drugs differently, in part due to variations (polymorphisms) in specific genes. The CYP450 genes affect how the body metabolizes selective serotonin reuptake inhibitors (SSRIs) as well as many other drugs. CYP450 genetic testing has been proposed as a means of guiding the use of SSRIs to improve the effectiveness of treatment for adults with depressive disorder.
EGAPP Recommendation Statement: The EGAPP Working Group found insufficient evidence to support a recommendation for or against use of CYP450 testing in adults beginning SSRI treatment for non-psychotic depression. In the absence of supporting evidence, and with consideration of other contextual issues, the EWG discourages use of CYP450 testing for patients beginning SSRI treatment until further clinical trials are completed.
EGAPP RecommendationExternal (December 2007)
Evidence ReportExternal (January 2007)
Summary ManuscriptExternal (December 2007)
CDC Summary of EGAPP Recommendation (May 2010)
Question 1 (Overarching Question): Does testing for CYP450 polymorphisms in adults entering SSRI treatment for non-psychotic depression lead to improvement in outcomes, or are testing results useful in medical, personal, or public health decision-making?
Question 2: What is the analytic validity of tests that identify key CYP450 polymorphisms?
Question 3a: How well do particular CYP450 genotypes predict metabolism of particular SSRIs? Do factors such as race/ethnicity, diet, or other medications, affect this association?
Question 3b:How well does CYP450 testing predict drug efficacy? Do factors such as race/ethnicity, diet, or other medications, affect this association?
Question 3c: How well does CYP450 testing predict adverse drug reactions? Do factors such as race/ethnicity, diet, or other medications, affect this association?
Question 4a: Does CYP450 testing influence depression management decisions by patients and providers in ways that could improve or worsen outcomes?
Question 4b: Does the identification of the CYP450 genotypes in adults entering SSRI treatment for non-psychotic depression lead to improved clinical outcomes compared to not testing?
Question 4c: Are the testing results useful in medical, personal or public health decision-making?
Question 5: What are the harms associated with testing for CYP450 polymorphisms and subsequent management options?
Why EGAPP Selected this Topic for Review:
Key Criteria: Depression is common and has significant health impact; SSRIs are commonly prescribed for depression in the US; FDA approved test with potential for impact on practice; potential for broad clinical application of the test for other drugs metabolized by CYP450 enzymes.
Other Considerations: A new technology with limited literature that challenges EGAPP methodology.