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Genetic Testing for Psychiatric Medications

Len Lantz, MD

Image: Biology by PublicDomainPictures (CC0)

Synopsis: How advanced and reliable is pharmacogenetic testing? Can genetic testing tell you your psychiatric diagnosis or tell you what medications will work for you? Read this article to learn more about genetic testing for psychiatric medications and a trick your doctor might not know.

BY LEN LANTZ, MD / 1.7.2020; No. 7 / 6 min read

Disclaimer: Yes, I am a physician, but I’m not your doctor, and this article does not create a doctor-patient relationship. This article is for educational purposes and should not be seen as medical advice. You should consult with your physician before you rely on this information. This post might also contain affiliate links. Please click this LINK for the full disclaimer.

Modern medicine is not as advanced as many people think

While you can learn some useful information about psychiatric medications from genetic testing (often called pharmacogenetic testing), it doesn’t tell you everything. It also does not teach your doctor how to accurately interpret the results. Genetic testing for psychiatric medications has been around for well over a decade, but genetics companies, such as GeneSight and GenoMind, are taking this testing to the next level. With a cotton swab of your cheek, they can run a myriad of tests accurately, efficiently and on a scale that makes genetic testing more accessible and affordable.

What is the main reason for genetic testing for psychiatric medications?

Genetic testing shows how the liver breaks down psychiatric medication, through different enzyme pathways. Most medications are broken down through two to five of these enzyme pathways. If one of these pathways has an abnormality in the genes which encode the enzyme, the enzyme won’t work. Therefore, the medication will not be broken down and removed from the body as quickly as predicted, and the blood level of the medication will rise to higher levels and possibly cause more side effects or toxicity. At the other end of the spectrum, if there are extra copies of genes that encode these enzymes, the extra enzymes will break down medications very quickly, preventing a person from benefiting from the medication because they can’t get the medication up to a therapeutic blood level.

Let’s look at genetic testing for a common antidepressant, Wellbutrin (bupropion)

Wellbutrin is mainly broken down through two enzyme systems in the liver, CYP2B6 and CYP2D6. What would happen if there were abnormalities in the genes that encode the enzymes of those two systems? Typically, if the genes that encode those enzymes are abnormal, the enzymes won’t work. If the enzymes don’t work, then your body will have a hard time breaking down or clearing Wellbutrin from your body. As you keep swallowing a Wellbutrin tablet each day, your blood levels will climb to toxic levels. So, what are the risks of having a toxic level of Wellbutrin? One of the main risks is a seizure. Wouldn’t you like to know if your genes are normal or abnormal? On the other hand, what would happen if you had extra copies of the genes that encode those two enzymes? Well, you would have extra enzymes to break down those medications, so even though you would be taking Wellbutrin each day, you would be unable to get your blood level of Wellbutrin high enough for it to help your depression.

What do the categories of genetic results indicate?

These genes and their enzyme systems are categorized by the number of copies of genes and whether or not these genes are normal or abnormal. Common enzyme systems that affect psychiatric medications are CYP2D6, CYP2C9, CYP2C19, CYP2B6, CYP1A2 and CYP3A4. Here is a layman’s explanation of what you might be able to expect from these different categories.

Poor (slow) Metabolizer (abnormality in 2 of 2 genes) – risk: abnormally high medication blood level; increased side effects or toxicity

Intermediate Metabolizer (abnormality in 1 of 2 genes) – risk: higher than expected medication blood level; increased side effects

Normal/Extensive Metabolizer (both copies of genes are normal) – medication blood level expected to be in the predicted range

Ultra-rapid Metabolizer (extra copies of genes) – risk: abnormally low medication blood level; inadequate response to a medication

Can I interpret my own genetic results?

I’m sorry to tell you that the answer is no. Interpreting genetic results can be very complicated. Some genetic abnormalities do not change the blood level of your medication. Why? This is because some of these enzyme pathways are 2nd or 3rd in line to the main pathway in the breakdown of a particular medication. Thus, having abnormal gene copies will not always result in a dramatic impact on a medication blood level.

Can you imagine how complicated these results can become if you are on several psychiatric medications? Psychiatric medications can compete for the same pathway, thus changing each other’s blood levels. When a person is on two or more psychiatric medications, they may benefit from a consultation with a pharmacogenetic expert to help them accurately determine their risks of drug-drug interactions, side effects and toxicities.

A trick your doctor might not know about

Can you just find out the blood level of a particular psychiatric medication that you’re on? Yes, you can. All psychiatric medications had to establish a therapeutic blood level reference range prior to being approved by the FDA. So, yes, you could have your doctor order a test to see if the blood level of a psychiatric medication that you are taking is in the normal reference range. It may take some searching for your doctor to find the correct laboratory testing code to order the test, but you should be able to obtain a blood level of any psychiatric medication that you are on. And, you could do this whether or not you first obtained genetic testing.

Will the testing reveal which medication will work for me?

Most doctors and patients wish the answer to this question was yes. Unfortunately, some genetics companies will prepare reports that make it look as though this is the case. There is currently only one test that demonstrates responsiveness to an antidepressant (a test that looks at the gene SLC6A4), and it mainly shows your likelihood of response to just one antidepressant medication, Lexapro (escitalopram). This test is not foolproof but it is helpful to some extent. Otherwise, there is limited research to show that genetic testing will reveal what medication will work for you.

What other genetic tests are commonly available?

There are some other useful genetic tests. One is HLA haplotyping. This is a test that can show you the risk of having a serious side effect, such as Stevens-Johnson Syndrome, to the commonly prescribed medication, Lamictal (lamotrigine), which is frequently prescribed for bipolar depression and as an add-on treatment for major depression.

Another genetic test that may be of value concerns MTHFR. This gene encodes an important enzyme that converts folate (a B vitamin) to L-methylfolate. Folate is a particularly important vitamin that ultimately helps to create neurotransmitters. Folate does not easily get into the brain through the blood-brain barrier, but l-methylfolate easily enters the brain. For people who have abnormalities in the MTHFR gene, they may benefit from supplementation with l-methylfolate in the treatment of mood and anxiety disorders. There is limited research to support supplementation with l-methylfolate, however, I have observed that about 10% of patients in my practice who abnormalities in both copies of their MTHFR gene see a clear improvement in depressive symptoms with supplementation with l-methylfolate.

Your doctor may have no clue how to read the gene reports

You may need help from an expert in interpreting reports from pharmacogenetics companies. This is because your doctor may not have been trained in interpreting these reports, which typically lump medications into categories that make the medications look “good”, “kinda bad” and “really bad.” Thankfully, genetics companies typically offer consultation support to doctors and patients so that people are able to accurately understand the results of their testing.

What if my genetics look normal, I’ve tried all the antidepressants under the sun and I’m still depressed?

There are many research-proven treatments for major depression. If medications have failed you in the treatment of your depression, you may consider meeting with a psychiatrist to determine if your diagnosis is accurate, if your psychiatric medication trials were of adequate dosage and if they were long enough in duration. There are several evidence-based psychotherapies that build your skills and are proven to help major depression. Other strategies that have shown efficacy in alleviating depression include high-intensity exercise and behavioral activation (a system of positive, scheduled activities). The gold standard treatment for depression which has failed to respond to regular treatment protocols is electroconvulsive therapy (ECT). ECT is a treatment that involves general anesthesia and introducing an electrical current into the brain to trigger a seizure. While this treatment may sound intimidating, it can be very effective and lifesaving. One of the newest and most effective treatments for treatment-resistant depression is transcranial magnetic stimulation (TMS). TMS may be slightly less effective than ECT, however, it does not involve general anesthesia or a seizure. See my article “Transcranial Magnetic Stimulation (TMS) – the Best New Depression Treatment” for more details.

Genetic testing may be right for you

If you have tried several antidepressant medications, and you have seen no benefit or experienced serious side effects, genetic testing may provide you some answers and some guidance. Many people are hesitant to try yet another antidepressant if they cannot reasonably predict whether or not they will get sick from another medication or understand why it might be that the medications are failing them. Parents who are considering starting their child on a psychiatric medication may also pursue genetic testing. The testing will not necessarily tell them whether a specific medication will help their child or not, but it may help parents and pediatricians determine ahead of time which medications pose the greatest risk of side effects.

Not all insurance companies will pay for this testing, but some insurance companies are recognizing that this testing may be appropriate for people who are not getting better with the usual treatment. Testing typically costs patients $300 - $350 if they choose to pay out-of-pocket. Many people would rather know if they could avoid possible risk or toxicity to medication for themselves or loved one, and they find the cost of testing is worth it.

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