CYP450 Genotyping to Predict Response to SSRIs Used to Treat Non-psychotic Depression in Adults: EGAPP™ Recommendation
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Depression is the number one cause of disability in the United States. Selective serotonin reuptake inhibitors (SSRIs) such as citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline are the most common drugs used to treat depression in adults. However, adult patients may not experience the benefits of SSRIs until 2–4 weeks after starting treatment, and only 50–60% of these patients will experience improvement of their depressive symptoms.
Patients metabolize or process drugs differently in their bodies due to a variety of factors. Variations (polymorphisms) in genes may be one reason why some people metabolize certain drugs well and other people do not. For example, the CYP450 genes affect how the body metabolizes SSRI drugs as well as many other drugs. CYP450 genotyping (genetic testing) is being proposed as a means of guiding the use of SSRI drugs to improve the effectiveness of treatment for adults with depressive disorder. The EGAPP™ Working Group examined the scientific evidence to see whether CYP450 genetic testing is valid and useful for this purpose.
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, EGAPP™ discourages use of CYP450 testing for patients beginning SSRI treatment until further clinical trials are completed.”
In 2007, the independent Evaluation of Genomic Applications in Practice and Prevention (EGAPP™) Working Group determined that there was not enough evidence to state whether CYP450 genotyping should or should not be used to help health care providers make decisions about beginning SSRI treatment in adults with non-psychotic depression. They discouraged use of such testing until more studies evaluating potential harms and benefits are conducted.
The EGAPP recommendation statement was based on the following key points from the evidence review:
- In studies of people undergoing SSRI treatment, the results of their CYP450 genotyping did not show a clear relationship with the actual levels of the SSRI drug in their blood.
- CYP450 genotyping results were not clearly related to how well the SSRI worked or the presence or severity of negative side effects.
- No evidence was found to indicate that the use of CYP450 genotyping improved health outcomes or helped patients or doctors make decisions about the use of SSRI drugs.
- The potential harms of CYP450 genotyping are:
- Increased health care costs without clear benefit to the patient.
- Patients may receive less effective treatment with SSRI drugs.
- Genotyping information may be used inappropriately for managing other drugs metabolized by CYP450 enzymes.
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