Can Genetic Testing Improve Your Mental Health Treatment?

Traditionally, psychiatric medications have been prescribed based on a trial-and-error approach. If a patient starts sertraline (Zoloft) but experiences persistent nausea, their provider might switch them to escitalopram (Lexapro). This process can feel extremely daunting to patients, but the truth is it’s really hard to predict a response to medication, so providers have to rely on their best judgment. I remember a patient who felt completely defeated after trying multiple medications for depression without finding relief. Through tears, she told me, “Maybe something's wrong with me and none of them will help me feel better.” What she didn’t know was that she might have been right, but for a reason she couldn’t control: genetics.

What Is Pharmacogenomics?

Pharmacogenomics (PGx) is the study of how your genes affect the way your body processes medications. In psychiatry, it’s one of the most promising advances in helping us move away from “trial and error” prescribing toward more personalized care. These genetic tests look at variations in genes that influence:

• How quickly or slowly your body metabolizes medications

• How sensitive your brain’s receptors are to certain drugs

• How likely you are to experience side effects or nonresponse

For example, if someone is an ultra-rapid metabolizer, their body breaks down medication so quickly that it never reaches a therapeutic level. On the other hand, a poor metabolizer processes medication too slowly, leading to higher levels in the bloodstream and more side effects.

A Real-World Example

When I tested that client using GeneSight, the results were eye-opening. She was, in fact, an ultra-rapid metabolizer for several of the most commonly prescribed antidepressants—explaining years of frustration and failed trials. But the test also revealed a few medications more compatible with her genetic profile. Together, we used that information to select a medication better suited to her metabolism. For the first time in years, she began to feel steady improvement. The experience was validating for her and reaffirming for me—it turned “Why isn’t this working?” into “Here’s why, and here’s what might help.”

The Evidence: Where Pharmacogenomics Works Best

Pharmacogenomic testing has the most research and evidence for conditions like depression and anxiety, particularly for patients who:

• Have not responded to at least two antidepressants

• Experience unusual or severe side effects

• Have family histories of poor medication response

While research is still evolving for other conditions, like ADHD, growing data supports its use as a decision-support tool, not a replacement for clinical judgment.

What Genetic Testing Can—and Can’t—Do

Pharmacogenomic testing doesn’t tell us which medication will definitely work, but it helps us rule out options less likely to help and identify those with a higher likelihood of success. Think of it as a map—it doesn’t take the journey for you, but it helps you avoid dead ends.

It can:

• Provide insight into why past medications didn’t work

• Identify more effective, better-tolerated options

• Reduce trial-and-error prescribing

• Improve confidence and adherence to treatment

It can’t:

• Guarantee a “perfect match”

• Replace the need for therapy, lifestyle changes, or ongoing follow-up

  
  

If you’ve struggled to find the right medication or felt discouraged by past experiences, pharmacogenomic testing may be worth discussing with your provider. Sometimes the missing piece isn’t effort—it’s information. And information, in this case, can be life-changing.

FAQ

What is GeneSight?

GeneSight is a genetic test that analyzes a patient's DNA to determine how they may respond to certain psychotropic medications, such as antidepressants, antipsychotics, and mood stabilizers. Additional included tests: COMT genotype and MTHFR variants.

Will GeneSight psychotropic testing be covered by insurance?

It’s covered by most major insurance companies, including Medicaid and Medicare. You can call GeneSight before you test to inquire about any copays or out-of-pocket costs.

Are there any criteria that I need to meet for GeneSight testing to be covered by my insurance?

Yes, insurance carriers may have slightly differing policies but generally require at least two medication failures.

References:

Oates JT, Lopez D. Pharmacogenetics: An Important Part of Drug Development with A Focus on Its Application. Int J Biomed Investig. 2018;1(2):111. doi: 10.31531/2581-4745.1000111. Epub 2018 May 27. PMID: 32467882; PMCID: PMC7255432.Pyzocha N. GeneSight Psychotropic Genetic Testing for Psychiatric Medication Selection. Am Fam Physician. 2021 Jul 1;104(1):89-90. PMID: 34264602.