I have treatment-resistant depression and have tried at least eight drugs which have all made me sick. My doctor says I have a high sensitivity to medication in general and is suggesting that I try medical genetic testing which my insurance may cover. Do you think this is a reasonable next step?

Picking the right antidepressant medication still involves too much trial and error. We certainly hope for a more scientific method for matching each person with the best treatment. Genetic testing may someday help with that process, but it doesn’t offer much practical help at this time.

When we think about using genetic testing to guide selection of medication, we can think about three possible uses.

First, we would hope that genetic testing might predict which medication, or type of medication, would work best for which individual. Unfortunately, no genetic tests (or other laboratory tests) have proven useful so far. Some small studies have suggested that specific genes or genetic variations might predict greater benefit from a specific medication, but those promising findings usually have not been confirmed by follow-up studies.

Second, if genetic tests cannot predict the most effective medication for an individual, we can still hope they might help chose the medication with fewer side effects. The early research in this area is a little more promising. This question is probably an easier one to answer because side effects of medication are often easier to pinpoint than benefits. But there are still not specific tests proven to predict side effects well enough so that we can recommend them for the real world.

Third, I suspect the tests your doctor mentioned would examine genetic differences in how medications are processed or eliminated from the body. Most antidepressants—and most medications overall—are processed in the liver by proteins called cytochromes. Specific cytochromes process specific medications. For some of these cytochromes, people vary significantly in how fast medications are processed. If your genes make you a slow processor for a specific medication, then the standard dose of that medication would last longer in your system and lead to a higher level in your body. And that could lead to more side effects. But being a slow processor (or slow metabolizer) isn’t all bad. If your body processes medication slowly, the standard dose might be too much, causing more side effects, but a lower-than-normal dose might be effective.

Genetic tests are available now to tell if you are a slow metabolizer of certain medications and that would mean that you would certainly want to start with a lower dose than most people. But your own experience is probably enough to tell you just that. Given your experience, you’d want to start with a lower dose than most people and increase the dose more slowly, hoping to see benefit before you see side effects.

That was my long answer. My short answer is genetic testing would not hurt, but it probably won’t tell you anything you don’t already know. If you are sensitive to the side effects of medications, that is true whether a genetic test agrees with you or not.

About the Doc

About the Doc

Greg Simon, MD, MPH, is a psychiatrist and researcher at  Kaiser Permanente Washington Health Research Institute in Seattle. His research focuses on improving the quality and availability of mental health services for people living with mood disorders, and he has a specific interest in activating consumers to expect and demand more effective mental health care.

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