How to Find the Right Antidepressant: Genetic Testing for Antidepressants

Antidepressants are medications that are prescribed as a treatment for depression and that is a complicated condition. By virtue of being a mood disorder, it is heterogeneous in character, which means that there are so many facets to it, all of which make it more complicated to even approach and let alone treat. As complicated as depression is, so are the individuals that it affects. Depression is often difficult to treat (or manage) as it can take a very long time—we’re talking months or even years—to find just the right and effective medication.

Despite it being a complicated condition, physicians have taken to treating depression by means of prescribing something and just hoping for the best. The decisions of which drugs to prescribe and which treatment paradigm to choose is loosely based on patients’ family history of mental illness along with as much information about symptoms as possible.

Add to this the fact that there are several kinds of antidepressant drugs on the market. There are the newer medications that are based on serotonin and norepinephrine (neurotransmitters that affect your mood) and that adjust the brain’s mood chemical levels. Furthermore, there are the older drugs, the tricyclic and monoamine oxidase inhibitors (MAOI) medications. Doctors often rely on trial and error in their treatment approaches to depression, which is why it should not come as a surprise that anywhere from a third to nearly 40% of those with depression do not respond at all to their first drug of treatment.

In other words, physicians have very little guidance during the treatment approach to depression.

However, that does not have to be the case anymore. The latest advancements in the realm of genetics have had a positive impact on the practicality of treating mood disorders and mental health. This progress has ushered into medicine a discipline that is called pharmacogenomics or pharmacogenetics. This term essentially refers to the studying the effect of genes on the body’s response to medication. In other words, these terms refer to drug-gene testing, or how drugs affect an individual’s genetic makeup. To be entirely specific, while the two terms overall refer to the same thing, there are slight differences. While pharmacogenetics is more specific in that it refers to one gene interacting to one drug, pharmacogenomics is more of a whole genome approach, taking in genomics as well as epigenetics as it looks at the effects of multiple genes on drug response. However, whichever term you decide to go with, the aim of either is the development of rational ways to optimize drug therapy by taking into consideration patients’ genotypes. All this with the ultimate goal to obtain the highest efficiency with minimal side effects.

how does all this relate to treating depression

So, how does all this relate to treating depression, you may wonder? Well, it turns out that there is testing available for depression patients that may indicate how well they respond to certain antidepressants. This response is what makes one patient different from another. In other words, not all depression patients respond to a drug the same way simply because they do not break it down the same way. This, in turn, is because their chemistry is different, meaning that they break down the drugs differently—or they have different receptors for brain chemicals—and this affects their response to drugs. At the heart of these differences are genes that code for the enzymes that break down the drugs as well as the receptors to which mood chemicals bind as a result of the drug.

Along those lines, an example of a genetic test that investigates a patient’s antidepressant drug response is GeneSight, a genetic test that takes into consideration a total of 12 genes that are involved in the breakdown of 56 various antidepressants. More specifically, as mentioned before, this panel entails genes that code for two main things. One is proteins, or enzymes, that are involved in the breakdown of key chemicals in the antidepressants. Another thing these genes code for are receptors for neurotransmitters (or simply brain chemicals such as serotonin or norepinephrine) that are targeted by the drugs.

What GeneSight does is it compiles the genetic activity information and bins the panel of antidepressants into three main categories that are color-coded into green, yellow, and red. It does not classify the drugs based on efficacy, but rather on the number of side effects they produce. In other words, the tests help doctors see which drugs cause the most issues for a specific patient and tell them to avoid those drugs. As such, a green category of drugs is said to have the least side effects, yellow is marked by moderate side effects and red with the most. In other words, the red category can be viewed as the most helpful as it provides the physicians with information about which drugs have the most powerful adverse side effects and as such should be avoided.

A study that has been conducted on the practicality of GeneSight reports that individuals who have used the test are 50% more likely to achieve remission after two months while being 30% more likely to respond to the test’s recommendations. This is compared to individuals who were treated without the test.

Overall, however, as promising as genetic testing seems in the realm of prescribing the most efficacious antidepressant for mood disorder such as depression, it is still far from being a clear instruction on exactly which drug to prescribe when. Rather, it is viewed as just another tool for physicians as they make their decision about how to approach treatment. Thanks to genetic testing, doctors are more informed about which drugs potentially have the least side effects and which drugs to avoid completely. And this is a great step toward even better personalized medicine.

Laura Day