Genetic Testing for Selection of Psychotropic Medications

GeneSight is a blood test to determine which neuropsychiatric medications are indicated for an individual based on genetic analysis. The test is expensive and not likely to be helpful for most patients.

Patients who suffer from major depression and other neuropsychiatric conditions usually improve with medication, but about half of patients fail to respond to the first drug they are given or experience intolerable side effects. It can take a long time and a lot of trial-and-error before the clinician happens upon one that works well. Even an antidepressant that worked well for a family member may produce an inadequate response for the patient. Up until now, there has been no way to predict how an individual will respond to a given drug. Now there is a test that offers to make such predictions: GeneSight psychotropic genetic testing. Unfortunately, it promises more than it can deliver.

Wouldn’t it be great if a blood test could tell you in advance how you will respond to a medication? That’s one of the many benefits that were anticipated when the human genome was first deciphered. Francis Collins predicted that mainstream medical practice would soon feature a genetic test followed by a prescription carefully chosen for the individual. One of the first candidates was gene-guided adjustment of Coumadin dosage. In a previous article, I argued that patients on Coumadin could be managed just as well without knowing genetic test results.

Greden et al. carried out the GUIDED trial to assess the impact of pharmacogenetics on clinical outcomes in patients with major depressive disorder who had failed one or more trials of antidepressants (mean number of failed medications 3.5). It was a large (1,398 subjects) randomized controlled trial comparing subjects whose doctors had access to genetic test results to subjects who were treated as usual without such information. Its findings: “Pharmacogenetic testing did not significantly improve mean symptoms but did significantly improve response and remission rates [to a small degree, on the order of 26% vs. 19.9%] for difficult-to-treat depression patients over standard of care.”

The GeneSight test can be performed on a single blood draw or on a buccal swab. It analyzes 57 neuropsychiatric medications and 12 genes. It is 100% accurate in detecting the genes, but according to the FDA only 13 antidepressants have enough pharmacogenetic evidence to warrant changes to therapy. Medicare covers the cost of $1,569 but not all insurance programs cover it. A report is provided with color-coded categories of “use as directed,” “moderate gene-drug interaction,” or “significant gene-drug interaction.” It includes clinical considerations such as “serum level may be too low, higher doses may be required.”

Conclusion: another expensive test that is unlikely to be useful

Natasha Pyzocha, DO, writing in American Family Physician, comments that “consumer marketing of this test may lead patients to believe that it can predict medication response, when that may not be the case.” She also says, “Routine genetic testing is not recommended. Choosing antidepressants based on health history and symptoms should still be the standard initial approach.” I agree.

This article was originally published in the Science-Based Medicine Blog.

Dr. Hall is a contributing editor to both Skeptic magazine and the Skeptical Inquirer. She is a weekly contributor to the Science-Based Medicine Blog and is one of its editors. She has also contributed to Quackwatch and to a number of other respected journals and publications. She is the author of Women Aren’t Supposed to Fly: The Memoirs of a Female Flight Surgeon and co-author of the textbook, Consumer Health: A Guide to Intelligent Decisions.

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