Did you know that your DNA is 99.9% the same as your neighbor’s? So what makes you you? That remaining 0.1% can influence everything from your height, weight, and hair color. It can also affect how your body reacts to and breaks down certain types of medications.
The emerging scientific field of pharmacogenomics combines pharmacology and genomics to understand how an individual’s genes interact with medications (you may see the term abbreviated to PGx, or used interchangeably with the term pharmacogenetics). This science allows healthcare providers in the mental health field and beyond to personalize treatment based on an individual patient’s DNA.
While this concept may seem very 21st century — in fact, its history stretches back millennia.
The earliest example of pharmacogenomics
To find the origin of pharmacogenomics, you literally have to go back centuries. In 510 B.C., famed philosopher Pythagoras, for whom the mathematical theorem is named, documented potentially fatal reactions among some but not all of his countrymen when ingesting fava beans.1 Though the understanding of genetics was a long way away, Pythagoras was onto something important: What happens to one person when they consume something may have a completely different effect on someone else. This is one of the core pillars of pharmacogenomics. (He was right; his observation eventually led to the discovery of G6PD deficiency.2)
With greater information available about the human genome and more research lending insights into the role genes may have on the variable effects of drugs, the field of pharmacogenomics has expanded significantly in recent years.
Uses of pharmacogenomics today
In the past 15 years, the field has shifted away from being exclusively an area of research and is now being used clinically, says Josh Peterson, M.D., a Professor of Biomedical Informatics and Medicine and Director of the Center for Precision Medicine at the Vanderbilt University Medical Center in Nashville, Tennessee. (Read a Q&A with Dr. Peterson on drug-drug and gene-drug interactions here.)
“We can measure genetic markers using a blood or saliva sample to predict drug responses,” Dr. Peterson says. That includes how likely a medication will work (or not work) in a particular person, who is at risk of adverse drug events (ADEs), and the optimal dose to prescribe. “Most findings relate to drug metabolism — how much of the drug circulates in the bloodstream,” he says.
Factors such as kidney and liver function are crucial considerations when doctors prescribe medications. Pharmacogenomics “is adding another dimension to what we think about when prescribing drugs,” Dr. Peterson says.
Pharmacogenomics can make taking medications safer
Whether it be for the heart medication or antidepressant you’re taking, pharmacogenomics can help by identifying which medications may be more likely to cause side effects, or at what dosages of medication an individual may be more or less likely to experience ADEs. This has significant implications since harmful side effects cause 1 out of every 5 injuries or deaths per year to hospitalized patients.3
For example, among individuals being treated for mood and anxiety disorders, pharmacogenetic-guided treatment has been associated with significant decreases in medication side effects.4
Pharmacogenomics can make treatment plans more effective
Individuals experience varied responses to many medications. As an example, in patients with depression, it’s been cited that only about ⅓ of individuals treated with an initial antidepressant are able to achieve remission.5 While many factors may be at play, many types of medications may have a genetic basis for inefficacy, or a lack of therapeutic response.
Pharmacogenomic testing can be crucial in that respect, because it signals which medications may be more likely to be effective, and which may be less likely to be effective, for an individual genotype. That points treatment towards relief of symptoms, which leads to the ultimate goal of remission. Some examples include:
- With clopidogrel, which is used for cardiovascular and neurovascular indications, there’s a strong genetic basis for therapeutic failure in some patients, Dr. Peterson notes.6
- Several meta-analyses (studies combining multiple different studies) of individuals undergoing treatment for major depressive disorder showed a greater than 70% increased odds of remission with PGx-guided treatment compared to treatment as usual.7,8
Pharmacogenomics implications for different healthcare specialties
“Some gene-drug relationships are so strong and of such concern that they are used routinely and mandated by the FDA,” Dr. Peterson says. In fact, the U.S. Food and Drug Administration (FDA) has created a comprehensive list of hundreds of medications that have pharmacogenomic biomarkers.9
To that end, the Clinical Pharmacogenetics Implementation Consortium (CPIC) has created, curated, and posted peer-reviewed, evidence-based, updatable, and detailed gene-drug clinical practice guidelines. Within this category are more than 65 drugs, including anticoagulants, antiplatelet drugs, immunosuppressants, antidepressants, and other psychiatric drugs.10
Barriers to the proliferation of pharmacogenomics — and its future in healthcare
One of the trickier aspects of putting pharmacogenomics to use is time. In other words, the quicker scientists conducting the PGx tests can identify your specific genotype, the faster your clinician can get the results they need to make an informed decision about prescribing and dosage. For that reason, the turnaround time of the test needs to be minimized, Dr. Peterson says. (You can get results from a company like Genomind in as few as three days or less.)
The hope is that going forward, pharmacogenomic information can be put in a patient’s medical record and used for future treatments. What makes genetic data so important is that it will never change during a patient’s lifetime.
Concerns over the cost of PGx testing represents another factor curbing its widespread use.11 This is due, in part, to inconsistent insurance coverage of the testing. Luckily, in recent years, more plans have expanded their coverage and reimbursement policies to include PGx (see Medicare, for example).
If you’re interested in pharmacogenomics for your treatment plan, ask your clinician if they’re familiar with precision health approaches. Facilitated by groups like Genomind, a precision health approach utilizes pharmacogenomic testing so that clinicians can more accurately prescribe and provide dosages for patients suffering from a range of mental health conditions. These include depression, anxiety, attention deficit disorder, and others. Through pharmacogenomic test results and the use of gene-drug software — with which your clinician can analyze gene-drug and drug-drug interactions — Genomind can help patients who may be taking everything from antidepressants, cardiovascular medications, agents for diabetes, and more. Get started today.
Sources
- Information on Pythagoras: Pharmacogenetics and Pharmacogenomics (2001)
- Discovery of G6PD deficiency: Glucose-6-phosphate dehydrogenase deficiency: a historical perspective (2008)
- ADRs mortality statistic: Preventable Adverse Drug Reactions: A Focus on Drug Interactions (2021)
- PGx testing led to significant decreases in medication side effects: A Naturalistic Study of the Effectiveness of Pharmacogenetic Testing to Guide Treatment in Psychiatric Patients With Mood and Anxiety Disorders (2015)
- One-third of individuals achieve remission with their first antidepressant: Questions and Answers about the NIMH Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Study (2006)
- Clopidogrel PGx guidelines: Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2C19 Genotype and Clopidogrel Therapy (2022)
- Genetic basis for antidepressant efficacy; PGx-guided treatment indicated 71% increased odds of remission: Pharmacogenetic tests and depressive symptom remission: a meta-analysis of randomized controlled trials (2019)
- PGx-guided treatment indicated 74% increased odds of remission: The effect of pharmacogenomic testing on response and remission rates in the acute treatment of major depressive disorder: A meta-analysis (2018)
- Information on biomarkers on drug labeling: Table of Pharmacogenomic Biomarkers in Drug Labeling (2021)
- CPIC gene-drug guidelines: Guidelines (2021)
- Cost barrier to PGx testing: What Are the Barriers and Enablers to the Implementation of Pharmacogenetic Testing in Mental Health Care Settings? (2021)
