Expert group discourages genetic testing for antidepressant dosage

amplichip_largethumbnail.jpgAccording to a study by an independent panel of medical and scientific professionals, there is “insufficient evidence to support a recommendation for or against use of CYP450 testing in adults beginning SSRI treatment for non-psychotic depression.” Although the study discourages current use of CYP450 testing, they wrote that further clinical trials should be completed before making a firm recommendation in either direction.

SSRIs are a family of commonly prescribed antidepressants. They include Celexa, Paxil, Prozac and Zoloft, and they act by influencing the activity of the neurotransmitter serotonin in the brain. Effective doses vary from person to person, and some researchers think that an individual’s genotype may affect how much or little of a drug a person needs to achieve a given effect.

In particular, the cytochrome P450 (CYP450) enzymes in the liver break down drugs in the bloodstream. That’s why people have to take drugs on a regular basis. But genetic variation in some CYP450 genes can lead to higher or lower enzyme activity, thus affecting the amount of drug circulating in the bloodstream. For this reason, doctors often have to adjust drug dosages to achieve a desired target range or clinical effect. The study of how genetic variation affects drug metabolism is known as pharmacogenomics.

A well-known pharmacogenomic effect is due to variation in the CYP2D6 gene. Most people respond to the painkiller codeine. But some individuals have a CYP2D6 genotype that results in insensitivity to the drug, while for others, codeine can have a noxious effect at dosages effective for the average person.

However, there have been far fewer pharmacogenomic studies on CYP450 variation and metabolism of SSRIs. The panel was concerned that diagnostic tests such as Roche’s AmpliChip CYP450 are being used without having been fully accepted by the biomedical community as useful. The authors thus set out to examine published studies on the AmpliChip test with respect to three standards of usefulness: technical accuracy, clinical validity, and clinical utility.

The group found that the AmpliChip product measures genotype well; it is technically accurate. But the group also found that the currently available crop of studies has not conclusively shown that variations in genotype affect SSRI levels in the bloodstream. Clinical validity is thus inconclusive. And to date, there have been no studies on clinical utility—that is, whether knowing CYP450 genotype leads to positive final outcomes such as improved patient quality of life or reduced treatment costs.

So it looks like a lot more research must be performed on the pharmacogenomics of SSRI dosage—not to mention a host of other health-related genetic associations—before we enter the age of personalized medicine.






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