The saying "if it seems too good to be true, it likely is" applies to so many things in life. As the director of the Clinical Pharmacogenomics Service at Boston Children's Hospital, I spend a significant amount of time discussing what pharmacogenomics testing cannot tell us. I am sure you are wondering why I would take a negative approach instead of touting the miracles of pharmacogenomics testing, since after all, that is my job. Well, as with many things, it is complicated.
Pharmacogenomics can potentially guide drug choices
Pharmacogenomics is the study of gene expression on the ability to metabolize or break down medications. The term "gene expression" is important because we're talking about how much your genes influence your response to a medication. Much like the director of a play or movie, your genes give instructions to other parts of your body. One of the things your genes direct is the production of enzymes required to break down (or "metabolize") the drugs you take. These enzymes influence how effective a drug might be for you and how likely you are to experience negative side effects. Your unique combination of genes is called your genotype. Your genotype can tell us if you will make more or significantly less enzyme than other people. These enzymes help break down the medications into substances that can be more easily excreted by the body. However, in some cases these substances can be active and some are even harmful before they are excreted. This partially explains why some people will get no effect at all while others end up in the hospital with severe side effects from the same medication at the same dose.
Many factors affect how you metabolize medications, including your age, gender, diet, whether or not you smoke, whether or not you are pregnant, your other medical problems, and very importantly, the other medications you are taking (including over-the-counter medications and herbal supplements). I often use the analogy of a pie to describe the effect of genetics on a medication's metabolism. In some cases, your genetics makes up a very large part of the pie — up to 90% for some medications. In other cases, your genetics are only a tiny sliver of the pie and the other factors make up the largest amount.
Using pharmacogenomics wisely is key to its usefulness
The key to applying pharmacogenomics is knowing when to test and how to apply the results. There are several situations where genetic testing before starting a medication is standard of care today. When there is a well-understood drug-gene interaction, knowing the genotype before starting treatment can avoid dangerous side effects. An example of this is a medication for the treatment of inflammatory bowel disease that, if metabolized slowly, can lead to a severely depressed immune system and life-threatening infections. In other cases, knowing that a patient will not respond to a therapy can save precious time and protect quality of life, such as for certain cystic fibrosis and cancer medications. As always, the goal is to match the right drug to the right patient to achieve the greatest benefit with minimal side effects.
Pharmacogenomic testing can be informative and can help caregivers and patients make safer decisions when choosing medications. However, promoting pharmacogenomic testing with application to only one disease state or with questionable testing practices can cause more harm than good. Most genes influence how the body metabolizes not just one class of medications, but can influence many other drug classes as well, and to different degrees. Focusing only on one condition, such as ADHD, and ignoring the influence that genotype may have on other drug classes, such as medications for heart disease, can actually result in patient harm. Overstating the impact of the genotype on the person's ability to metabolize medications can also cause serious anxiety. Patients have reported feeling scared to take any medications, even when they know that their condition will not likely get better without treatment.
And this is why during each visit, we spend a significant amount of time discussing what pharmacogenomics cannot tell us. And then we talk about whether testing might make sense. For patients who have had a long history of serious side effects from various medications or failure to respond to medication, testing can help explain what has gone on in the past as well as help guide future decisions. In one memorable case, the patient was extremely grateful for results that explained why she had experienced debilitating insomnia while on fluoxetine. She told us that previous healthcare providers had told her it was "all in her head" when actually it was her inability to metabolize the drug at standard doses. For others, results predicting and thus avoiding life-threatening reactions to anti-epileptic drugs help design a more appropriate regimen for seizure control.
While the science of pharmacogenomics has been around for a hundred years, we are still at just the tip of the iceberg in understanding that information and using it to improve the lives of patients. There has been an explosion of knowledge over the past 10 years and we learn new things every day. It is an exciting time to be studying pharmacogenomics!