Want to Stop Dating Antidepressants and Find “The One”?

Why the need for such tests? There are 28 generic drugs—and dozens more brand names—that fall into the FDA-approved drug classes for depression. These categories include:

• Tricyclic Antidepressants (TCAs)
• Monoamine Oxidase Inhibitors (MAOIs)
• Selective Serotonin Reuptake Inhibitors (SSRIs)
• Selective Serotonin/Norepinephrine Reuptake Inhibitors (SNRIs)
• Dopamine Reuptake Inhibitors (DRIs)
• 5-HT2A Receptor Antagonists
• Serotonin Reuptake Inhibitors (SRIs)
• Tetracyclic Antidepressants (TeCAs)

That’s a lot of medication first dates right there. PGx testing helps narrow down the options. “It gives clues or ‘breadcrumbs’ about what class or type of medicine you may or may not be suited for,” says nurse practitioner Amy Edgar, CRNP, APRN, founder of Blackbird Health, a mental health practice in Eastern Pennsylvania. “So it gives ideas both about the medication class and, within that class, specific meds for prescribing and individualized dosing.” 

Genetic Tests at Their Best

To determine the right drug type for you, docs consider a variety of factors: symptom severity, which side effects you can tolerate, other prescriptions you take (and potential drug interactions), other health conditions you have, your risk profile for additional issues, and—if you take a PGx test—how well you metabolize things. 

Testing mainly looks at cytochromes, or CYPs, in the liver, proteins that metabolize most medications and make them available for use, says Kristine Ashcraft, medical affairs director of pharmacogenomics at Invitae, a genetic testing company. That info can tell you a thing or two about how your body will react to various drug types and dosages. Specifically…

Testing Can Help Determine: which medications to try
Explain It To Me: The rate at which you break down medications is perhaps the biggest clue to finding the correct one, says Edgar, an early adopter who has used genetic testing to guide treatment for the past two decades. You might metabolize certain compounds faster than others. For example, genetic testing showed one Mental reader how speedily she metabolizes dopamine. “Since I am burning through my natural supply so quickly, my doctor prescribes medication with extra dopamine,” she says.

Testing Can Help Determine: your best starting dose
Explain It To Me: There are dosage guidelines for every medication, but they’re based on generalizations. If you are an intermediate or poor metabolizer, a drug will hang out in your system a lot longer than it would for most, so a typical starting dose might be too much or put you at greater risk for side effects. 

On the other hand, rapid metabolizers may need a higher dose to ensure therapeutic effects last as long as needed. If you’ve ever had to keep increasing a med’s dose and it seems like nothing’s happening, it might not be an issue with the drug, but the dose itself.

“Often, prescribers are not comfortable continuing to raise your dose multiple times, so you feel like the med has failed, when in fact it’s just how you are metabolizing it and, if adjusted, it might be the right one,” says Edgar. “These are things you can’t know without a genetic test.”

Testing Can Help Determine: how likely you are to have an adverse reaction
Explain It To Me: Traditionally, doctors rely on FDA guidelines and family history as hints to potential side effects, which are a normal part of starting a new medication. Most antidepressants take four weeks to mesh with your system, and it’s not exactly a honeymoon phase. Common side effects of a new antidepressant may include: 

• headache
• nausea
• weight gain
• dry mouth
• dizziness
• interruptions of sleep cycle (drowsiness or insomnia)

What concerns doctors most, however, are not intermittent and low-grade early issues like a headache or stomachache, but adverse effects, which are unexpected or dangerous physical or psychological reactions to a drug. If the side effects listed above continue or get worse after the initial month-long trial period, you’re probably having an adverse reaction. Call your doctor immediately; they will likely pull you off the medication.

Which brings us back to metabolism, and why knowing it can be so helpful. People who metabolize medication very slowly, for example, are at higher risk of having an adverse reaction to any drug, though the exact reaction differs from drug to drug. Take a pain treatment like Percocet: A slow metabolizer is more likely to feel loopy and dizzy, more quickly and intensely, than someone with a normal metabolic rate. 

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With antidepressants, slow metabolizers aren’t able to break down a typical starting dose properly or effectively—which means not knowing whether that med could actually work at a different dose and being more susceptible to very scary stuff like suicidal thoughts. 

Most medications used for mental health are metabolized by one of two genes, CYP2D6 or CYP2C19. “There are two studies linking variations [of these genes] to suicidality, specifically for 2C19 and citalopram or escitalopram,” says Ashcraft. (Those are types of antidepressants.)

“The likely reason is that poor metabolizers of 2C19 are exposed to more of the medication at standard doses, as they cannot metabolize the medication well,” Ashcraft continues. “Over time, this builds up and causes adverse effects, somnolence [drowsiness] being the most common dose-dependent issue. Somnolence has been associated with increased suicide risk.” A PGx test can tell whether you have changes in your 2C19 and 2D6 genes—in which case, such a medication would either never be prescribed or started on a lower dose.

“This is where tests matter very much, and they matter in a way of life or death,” says Edgar. “Side effects are a normal part of onboarding a drug, but without a test done, it is hard to tell what side effects will quickly become adverse reactions, and it can become dangerous very quickly.” Of course, a good psychiatrist will insist on lots of communication when starting a new medication, and these conversations should help catch problematic issues early on.

Skeptics of Pharmacogenomic Tests Say…

Not all experts rate these tests a 10/10. One psychiatrist told us that doctors can take a cheaper blood level and find out how you’d metabolize a few medications, which is true. But therapeutic drug monitoring of this type has to be repeated over time.

Edgar sees the value in a PGx test through a wider lens, beyond leading you to the right antidepressant. The true value, in her opinion, is that once you find out what type of metabolizer you are, it can guide you through medicating your entire life. 

This is the reason Ashcraft describes PGx testing as “a seatbelt for medication management.” If you have variations in that 2C19 gene, for instance, “it doesn’t just impact mental health meds, but also medications used in cardiology, gastroenterology, infectious disease, neurology, pain management, and reproductive health. And that is just one gene,” she says. “Like an allergy, the information from a PGx panel needs to be stored and used for life every time a medication decision is made.”

We spoke with several experts who point to a lack of evidence for genetic testing. Particularly, that there hasn’t been a “major study that solidifies the benefits,” says Rashmi Parmar, M.D., a psychiatrist at Community Psychiatry in Newark, California. Dr. Law questioned the “inconsistent findings of benefit.”

Still, a 2018 study published in the journal Pharmacogenomics showed that people receiving therapies for depression based on pharmacogenetic testing were 1.71 times more likely to achieve symptom remission. In another study on depression and anxiety treatment, using PGx tests resulted in higher levels of improvement, with more significant response and remission rates. (These weren’t super-small studies, either: The first included over 1,700 people; the second, 685.)

And though not all insurance plans pay for genetic tests, a number of positive changes have recently gone into effect. Medicare started covering genetic testing panels in 2020, as did United Healthcare, says Ashcraft. And in April of last year, Blue Care Network (BCN) launched a program called Blue Cross Personalized Medicine, which uses genetic testing for certain members for a variety of diagnoses, including behavioral health.

Dr. Law says insurers are more likely to cover a PGx test if you’ve already tried several meds and haven’t found relief. Currently, legislation is pending in California to require pharmacogenetic testing before prescribing any drug.

The out-of-pocket cost for a PGx test used to hit the thousands, but a typical price tag today is between $200 and $400. (One study concluded that, even at $2,000/test, “pharmacogenetic testing among moderate to severe major depressive disorder patients…resulted in cost savings.”)

“The value proposition I explain to families is that your genes aren’t going to change,” says Edgar. “This test is static—it’s how you’re built. You can reference it for the rest of your life, so I tell my patients to view it as a health investment.” In her experience, most testing companies offer patient support, which may include payment plans or discounts.

Testing, Testing, 1, 2, Me?

Ready to swipe right on a genetic test? You can ask your medical provider about PGx testing, but it likely won’t be offered as a first step in depression treatment, says Lucia Wallis Smith, LPC, a psychotherapist in Princeton, New Jersey. Several of her clients have found success with genetic testing, but in particular circumstances. When multiple meds aren’t working the way they should, Smith uses genetic testing to help pinpoint why.

“Genetic testing is more widely used than in years past; however, it is still only used by about 10 percent of prescribers,” says Edgar. “While the evidence is mounting and the science supports it, we still haven’t reached that critical mass where everybody realizes this is what we have to do.” 

If you’re interested in genetic testing but “your doctor or prescriber does not know how to interpret your test or declines the use of it,” says Edgar, “take it to your pharmacist.” A pharmacist is an expert on knowing and interpreting how drugs break down. They’ll keep your test on file and “run meds through your profile to see if there are changes or problems,” explains Edgar. “That is an easy way to not have to interact with five different providers who don’t know or aren’t interested in using the information.” 

You can also point your doctor toward guidelines from the Clinical Pharmacogenetics Implementation Consortium, an organization that collates peer-reviewed evidence and suggests which drugs or genes would benefit from genetic testing. Even the FDA sees the advantages. “Pharmacogenetic tests, along with other information about patients and their disease or condition, can play an important role in drug therapy,” says the FDA’s site. “Knowledge of a patient’s genotype may be used to aid in determining a therapeutic strategy, determining an appropriate dosage, or assessing the likelihood of benefit or toxicity.”

Like any mental health treatment, PGx drugs aren’t a magic solution, but one tool in the proverbial chest. “There are amazing psychiatrists out there who use genetic testing, but who also have astounding experience and knowledge on how to tweak dosages and combinations of medication to improve people’s lives dramatically,” says Smith. “Genetic testing alone is not the key, but it could someday be a resource that makes a difference for you.” 

Additional reporting by Elizabeth Millard