One explanation for why we experience Side Effects? Understanding Your Genetic Response to Antidepressants

Antidepressants often play an essential role in helping patients with their mental health conditions. But as many patients can attest, it’s frustrating when certain medications either cause side effects or don’t work as intended.

You might experience insomnia, sleepiness or weight gain when taking one antidepressant, for example. Yet on a different medication, you might not have any side effects.

Or you may have a friend or family member who’s able to take a certain antidepressant with no problems – when you’ve been unable to tolerate it.

Some answers to these puzzles about antidepressants may be found in pharmacogenomics. That’s the study of how an individual’s genetics affects the body’s breakdown of or response to medications.

Why is Pharmacogenomics Important?

Pharmacogenomics is an emerging field of study. It holds promise for improving care and making treatment plans more personalized. If you and your physician know more about your genetic makeup, you could have a better understanding of which medications may require dose adjustments, may come with an increased risk of side effects, or may be less likely to work.

One way clinicians learn more about their patients is through genetic testing.

“Pharmacogenetic testing can indicate how patients may respond to medication for mental health care, [potentially] shortening time to effectiveness and decreasing likelihood of side effects,” said Nina Sperber, PhD, associate professor in population health sciences at the Duke University Clinical and Translational Science Institute, in an article on the institute’s website.

Key Genes

Our bodies rely on enzymes to process medications. Enzymes are proteins that help perform chemical reactions in the body, also known as metabolism. They’re essential for healthy bodily functions.

Genes come into play by providing the instructions for producing enzymes. Our genes – which make us unique – might have variations that could cause us to metabolize medications too quickly or slowly.

One of the most important groups of enzymes in metabolizing drugs is the cytochrome P450 family, which is found throughout the body but concentrated in the liver. Also known as CYP450, these enzymes influence how drugs are broken down and how long they stay in your system.

Two specific enzymes in the CYP450 family – CYP2D6 and CYP2C19 – account for a large portion of the breakdown of antidepressants.

Depending on your genetic makeup, these two enzymes may have either little or no function, causing some antidepressants to break down slowly. Or they may be particularly active, leading to rapid breakdown of some antidepressants. Or they could have normal activity.

Understanding Rates of Metabolism

The way these and other enzymes function determine how you may break down certain antidepressants. Researchers have developed a classification system that includes four rates of metabolism:

Poor metabolizer: Medication is broken down very slowly. This may increase the chance of having side effects as you may maintain high levels of the drug in your bloodstream for longer periods.

Intermediate metabolizer: Slower-than-normal rate of metabolism, also possibly leading to side effects.

Extensive metabolizer: Normal rate of metabolism. At standard doses, you are expected to have a normal amount of medication in your system.

Ultrarapid metabolizer: Medication is broken down rapidly. You might not get relief from your symptoms because the drug is removed quickly from your body.

The Benefits of Pharmacogenomic Testing

A genetic test analyzes your DNA. It gives your doctor information about how you may metabolize certain medications based on your genetic makeup.

Your doctor can use this information along with other clinical factors to help inform their treatment decisions. They may recommend a medication that’s less likely to cause side effects. The doctor can also use the information to adjust the dosage based on your genetic results.

Testing gives your provider more information to help inform your treatment.

A pharmacogenomic test might be helpful for you if:

• You’ve experienced significant side effects from taking an antidepressant
• You’ve not found an antidepressant that’s effective for you
• You’re starting a drug that’s known to have high genetic variability in how it’s metabolized

Limitations of Testing

Pharmacogenomic testing can provide valuable information, but as with most medical tests, it’s important to keep some limitations in mind.

For example, factors such as age, diet, other medications you’re taking, and your overall health can influence how well you respond to antidepressants.

Another consideration is that the field of pharmacogenomics is evolving. There are many things about genetics and medications that researchers don’t yet know. Pharmacogenomics is an example of personalized medicine, also called precision health – a promising, but relatively new approach that takes each patient’s individual characteristics into account.

Cost is another factor. Many insurance plans, including Medicare, cover all or a significant portion of a genetic test. Ask your provider or health plan about the cost before proceeding.

Getting Tested

The first step in pharmacogenomic testing is to discuss with your healthcare provider whether it’s appropriate for you. If so, your doctor will take a swab inside your cheek or order a test kit to be delivered to your home for you to collect the sample yourself.

The sample then goes to a lab for DNA analysis. Your doctor will get the results and schedule you for a visit to review them and discuss any potential medication adjustments as part of your comprehensive treatment plan.

With the GeneSight Psychotropic test, results are typically returned to your provider in a few days.

Understanding your genetic profile and how it could impact any antidepressants or other medications you take is an important step toward improving your mental well-being. It’s an especially valuable step for anyone who’s struggled with side effects or hasn’t seen improvement through the medications they’re currently taking.

For more information about this topic and other topics, please visit:

https://genesight.com/genetic-insights/fast-slow-or-in-between-how-your-genes-affect-medication-success/

https://genesight.com/genetic-insights/factors-that-may-impact-medication-response/