How we can address antidepressant mismatch

Antidepressants are one of the most widely prescribed types of medication in the United States, with about 11% of the population currently taking some kind of antidepressant (1). Additionally, it is very common for patients to go through multiple antidepressants before they find the right one. This can take several months and effort from the patient to continue treatment. It can be extremely expensive and discouraging to go through multiple antidepressants that are not helping the patient and that may be worsening their symptoms. When it comes to Major Depressive Disorder, only about 30% of patients achieve full remission with antidepressants. Many factors contribute to the mismatching of antidepressants with patients. One of the factors, which is the most important one for this article is the variability of patient responses to antidepressants.

In this article, I wanted to address this issue by providing a possible solution. This Solution involves doing genetic testing for the P450 enzymes, also known as CYP enzymes. The P450 Test is a pharmacogenetic test that looks specifically at the cytochrome (CYP) P450 enzymes, which can be found throughout the body but are more commonly found in the liver. The test requires DNA from the individual being tested, which can be acquired either through a buccal swab or blood draw. The DNA sample is then analyzed to identify specific alleles in the genes found in CYP enzymes, such as CYP2D6, CYP2C19, CYP1A2, and CYP3A4. CYP enzymes are responsible for breaking down foreign substances found in our body, such as medications and drugs so these substances can be excreted properly. The information provided by this kind of test is the category of metabolizer type that best fits the individual. There are four main categories created by gene variations: Poor, intermediate, extensive, and ultrarapid metabolizer, from slower to fastest enzyme activity respectively. This information can be useful because the metabolizer level helps clinicians determine which antidepressants would be most beneficial for the patient and which would be best to avoid. For example, individuals with a poor metabolizer profile for CYP2D6 may experience increased side effects with drugs such as fluoxetine or paroxetine. For more examples and suggestions on what to prescribe, visit the CPIC Guidelines provided in the references (2).

By understanding what type of metabolizer the patient has, it becomes easier to match them with the correct type of antidepressant. However, a few issues come to mind when developing this approach, including insurance coverage, the time required for the pharmacogenetic test to give results, and practicability. I am unsure how long it would take for the test results to return from the lab. Additionally, while this method could improve the matching rate of patients to antidepressants, it may not be the most effective approach. Nonetheless, it is a viable option to consider.

I encourage psychologists and psychiatrists to consider this an ethical issue. Prescribing the “go-to” antidepressant to a patient without assessing the patient’s unique biological profile can be harmful for them. It can be argued that current clinicians are doing a “trial-and-error” approach every time they prescribe a medication without knowing the patient’s biological profile. Of course, the approach suggested in this article does not lead to a 100% match rate, but it would be a step closer to more efficacious treatment options.

What’s your opinion on this issue?

References:

1-      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8633963/#:~:text=Antidepressants%20are%20one%20of%20the,several%20billion%20dollars%20%5B1%5D.

2-       https://cpicpgx.org/guidelines/cpic-guideline-for-ssri-and-snri-antidepressants/