An independent panel has recommended against the routine use of genetic testing for cytochrome P450 polymorphisms in adults with depression treated with selective serotonin reuptake inhibitors (SSRIs).
The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group is a non-federal group funded through a Centers for Disease Control and Prevention initiative to address the growing number and availability of genetic tests. Of the over 1200 genetic tests now clinically available, only a handful of clinical guidelines based on rigorous evaluation of the evidence exist to guide clinical decision making. EGAPP was established to develop and evaluate a systematic approach to assessing emerging genetic testing. The CYP450 recommendations are the first published by the group and are available here, or in the December issue of the journal Genetics in Medicine.
Nonpsychotic depression is a major public issue (with a lifetime prevalence of 16 percent) and can be personally debilitating. SSRIs are often used as first-line drugs of choice because of their relative tolerability and safety as compared to other categories of anti-depressants. However, it can take as long as two to four weeks before it is known whether a patient will respond to a particular drug or dose of drug. Patients and clinicians often go through several rounds of trial and error before finding the right drug and dose. And 12 percent to 15 percent of patients end up discontinuing use because of unacceptable side effects. A test to shorten that therapeutic window, or that could identify patients at risk for adverse reactions, would significantly benefit public health.
The cytochrome P450 family of genes play a major role in metabolizing drugs, including SSRIs, and it has been suggested that variations in those genes could be important in determining how well a person responds to SSRI treatment. Commercial testing for CYP450 genetic variations is now widely available. To assess the use of CYP450 testing, EGAPP undertook a methodological review of the evidence and concluded that there is insufficient evidence at this time to support a recommendation for or against the use of CYP450 testing for adults who are initiating treatment with SSRIs. Based on other contextual issues, EGAPP discouraged the use of testing until further studies could be done. The recommendations go on to outline clinical studies that should be done to clarify the clinical use of CYP450 testing in depression.
Full text of the recommendations