CYP2D6 polymorphisms: How Your Genes Affect Medication Response

When you take a pill, your body doesn’t treat it the same way everyone else does. That’s because of CYP2D6 polymorphisms, genetic variations in the enzyme responsible for breaking down over 25% of commonly prescribed drugs. Also known as cytochrome P450 2D6 variants, these differences can make a drug work too well, not well enough, or even turn it toxic. If you’ve ever been told a medication didn’t work for you — or gave you side effects others didn’t get — your CYP2D6 genes might be why.

This isn’t theoretical. People with certain CYP2D6 variants process codeine into morphine too fast, risking overdose. Others break down antidepressants like fluoxetine or venlafaxine so slowly they build up to dangerous levels. Even tamoxifen, used for breast cancer, needs CYP2D6 to become active — if your enzyme is weak, the drug might not work at all. These aren’t rare edge cases. Up to 1 in 10 people in some populations are poor metabolizers, and 1 in 3 are ultra-rapid. That’s why pharmacogenomics, the study of how genes affect drug response is moving from research labs into real clinics. It’s not about guessing what will work — it’s about using your DNA to pick the right dose, or the right drug, from the start.

CYP2D6 polymorphisms don’t just affect one class of drugs. They influence painkillers, heart meds, antipsychotics, and even some cancer treatments. And they interact with other factors too — like age, liver health, or other medications you’re taking. That’s why genetic testing, a simple cheek swab or blood test that identifies your CYP2D6 profile is becoming more common, especially before starting long-term treatment. Some hospitals now screen patients before prescribing certain drugs. You don’t need to wait for a crisis. If you’ve had bad reactions to meds, or if your doctor keeps adjusting your dose without clear results, ask if CYP2D6 testing could help.

Below, you’ll find real-world stories from people who’ve dealt with these issues — from unexpected side effects to meds that just didn’t work. We’ve pulled together guides on how to talk to your doctor about genetics, how to interpret drug interactions, and how to spot when your body might be reacting to a medication in a way that’s not normal. This isn’t about science fiction. It’s about making sure your next prescription actually works for you — not just for the average person on the label.