This is a question I’ve asked myself since genetic testing first came available around 2011. While the idea of a test to match the right medication with the right person is very appealing, my colleagues always cautioned that the testing available was helpful in telling you which medications may hurt or be ineffective and less useful in telling you what medication would be effective. However, over the last year, I’ve taken a second look at testing especially with treatment resistant patients; these are patients who have been to multiple psychiatrists and have tried multiple medications either without any relief or without substantial relief. In this next article, I will highlight a few cases in my private practice where genetic testing gave surprisingly helpful results that I otherwise would have never known and using that information has led to improved quality of life for patients as well as new lessons for me.
The testing process itself is pretty painless. You just have to swab your cheek for 30 seconds either in the office or at home and then mail it back in the provided envelope. Results are available within 3 days after it has been received to be processed. I can access the results through a physician portal as well as consult with the testing company to discuss and ask questions about the results. I then provide a copy of the results to the patient and discuss the report in detail with them including recommendations. The test results are divided into 3 major sections: 1) the gene variations: the patient’s genetic results and clinical significance of each gene, 2) the gene drug interaction summary which provides information about how the patient’s genetic profile interacts with medications commonly used in psychiatry, and 3) summary pages: the diagnosis-specific summary page will provide a visual plot of drugs for a particular condition.
This past week I reviewed the results with a young man with Bipolar Disorder who had been mostly unstable the past 3 years until fairly recently. He did have a genetic result that is a marker for Bipolar Disorder which was obviously not a surprise. We also came to understand why he could not tolerate 4 medications he had taken in the past year before we switched to a better choice. There was also a recommended medication list that he could potentially do well on in the future with less risk of side effects. Finally, we learned that he is a carrier of a gene that is found in 30% of Caucasians in which his mood is very responsive to exercise which he never realized before. Usually, patients with this result describe 3 days of weekly exercise as not being much exercise, while patients without this gene often describe 3 days a week of exercise as a significant amount. Patients without this gene may have no mood improvement with exercise. Even though as a physician I always recommend exercise to patients, I now understand that the vast majority of people I see will not see a clear mood benefit with exercise.
Another patient I have been treating for 2 years for anxiety and depression has not done particularly well on any of the medications she has been tried on. However, the stress of the pandemic has clearly complicated the issue for this person who had been unable to start her career after graduating college in 2020. I ordered a genetic panel on her a couple months ago and the biggest surprise is that she has a very strong Bipolar Disorder marker despite never having any symptoms of this disorder so far in her life (she is currently 22 years old). She still may develop this disorder later on in life and there is a family history of Bipolar Disorder in a maternal uncle. My colleagues have suggested that in situations like this, they have had success in treating the genetic result whether the patient will ever manifest symptoms of Bipolar Disorder or not; that would suggest focusing on mood stabilizers rather than antidepressant or antianxiety agents. The patient is open to us moving in that direction and I believe that is something I would have never realized so soon without genetic testing.
I’ve now had patients who were previously diagnosed and treated for Attention Deficit Hyperactivity Disorder (ADHD) with minimal benefit and who still have difficulty with focus, memory and a sense of well-being. The genetic result for some of these patients reveals they have an increased level of an enzyme that breaks down the neurotransmitter, dopamine, in their prefrontal cortex (this is the front third of the brain that supervises abilities such as time management, judgment, impulse control, planning, and organizing). The treatment for this condition is a medication that inhibits production of this overactive enzyme and not an ADHD medication.
80% of patients have a genetic variation of another enzyme responsible for the conversion of folic acid to methylfolate, which is a necessary cofactor for neurotransmitter synthesis. Some of these variations can result in a 55-75% reduction in enzyme function that according to recent studies require patient supplementation with L-methylfolate in order for their depression to improve. I would have never known this without testing for it specifically.
One limitation I have found with some testing results is that there can be two separate gene results that offset each other in terms of their actual effects and make it a bit unpredictable about how a person may truly respond to a particular medication. The other limitation is that there is no guarantee the person will do well on a recommended medication but more times than not the testing results offer helpful guidance.
Finally, you may ask is it worth it just to test everybody? I would say there is a cost/benefit equation here and there are many straightforward situations where the patient responds well to the initial intervention without testing. On the other hand, it can be a real advantage to have a patient’s genetic information prior to prescribing and possibly running into problems. The test can specifically tell me to bypass certain medications if the results suggest a higher risk of side effects such as weight gain, skin rash reactions or that this patient gets rid of a particular medication too slowly or too quickly—both can be problematic. Genetic testing shortens the trial-and-error process from one year down to three months or less. Finally, the cost of genetic testing has decreased considerably in recent years. Even if insurance won’t cover the test, the out of pocket expense has gone down from $750 to the current price of $400. If that is still too expensive, consider consumer testing that can be as low as $59 with FamilyTreeDNA or MyHeritageDNA which seem to take turns offering their service on sale. Both of these companies offer a similar genetic panel that can be used diagnostically or when choosing psychiatric medication if your psychiatrist is familiar with interpreting the results. I now believe the cost/benefit equation is becoming an important discussion to have with each patient just so they know about it and especially if they are struggling and are looking for a way to increase the chances of getting better sooner.