Pharmacogenomic testing is a cutting-edge tool in personalized medicine that uses your DNA to help predict how you will respond to certain medications. In both everyday practice and specialized care, this testing guides treatment decisions for drugs ranging from antidepressants like fluoxetine, citalopram, and paroxetine to pain relievers (like codeine, tramadol, morphine) and even treatments for addiction like naltrexone.
By understanding your unique genetic makeup—including key genes like CYP2D6, CYP2C19, and OPRM1—prescribers and I can tailor prescriptions to be safer and more effective for you. This helps define what may help and what can hurt and cause side effects.
Now, as you know, I work with people to taper medications that cause side effects, are ineffective, or are no longer desired. Oftentimes, people are prescribed medications for mental health at a time in life, and over time, they become unnecessary.
What Is Pharmacogenomic Testing?
Pharmacogenomic testing (often abbreviated PGx) examines how genes affect your body’s medication response. It looks for genetic differences that influence drug metabolism, transport in the body, and interaction with cellular targets. The goal is to predict which medicines (and what doses) will work best for you while minimizing side effects.
Liver enzymes
Our DNA contains instructions for making enzymes in the liver that break down drugs. Variations in the genes coding for these enzymes can make them work faster or slower. Some people eliminate a drug quickly and get little benefit, while others break it down slowly, increasing the risk of side effects. Pharmacogenomic testing identifies such genetic variants so that we can adjust treatment accordingly.
Key points about pharmacogenomic testing:
It is usually a one-time DNA test (since your genes don’t change). Your saliva, cheek swab, or blood sample is taken and sent to a lab for analysis—the lab checks for specific gene markers that affect drug response and sends back a report.
The results typically tell if you have specific versions of drug-processing genes. You might see terms like poor metabolizer, intermediate metabolizer, normal (extensive) metabolizer, rapid metabolizer, or ultra-rapid metabolizer for enzymes such as CYP2D6 or CYP2C19. These categories describe how active your enzymes are. A poor metabolizer has little to no enzyme activity (processes the drug slowly), whereas an ultra-rapid metabolizer has extra-high activity (processes the drug very quickly).
Pharmacogenomic reports may also include genes for drug targets. For instance, variations in OPRM1, the mu-opioid receptor gene, can influence how one experiences pain relief or responds to medications like opioids.
Case example: Laura had a dental extraction and took an opioid for pain when Tylenol did not reduce the pain. She awoke in the middle of the night in searing pain on her right side, near her liver. Once she recovered, we did a PGx test on her, which revealed she would not tolerate opioids and she should avoid them. Opioids can indeed cause gall bladder spasms, which we believe she experienced.
Why Should Everyone Consider Pharmacogenomic Testing?
Taking a “one size fits all” approach to prescribing can lead to trial-and-error with medications. Pharmacogenomic testing offers several potential benefits for both patients and providers:
Finding the Right Medication Faster: If you’ve ever had to switch medications due to side effects or lack of effect, PGx testing might help avoid some of that. It can hint at which drugs are more likely to work for you (or which to avoid), especially in fields like mental health and pain management.
Dose Optimization: Your genetics can affect how much of a drug you need. Many of my clients say, “Oh, I am very sensitive to medications and herbs.” I usually need much less than is prescribed. This is a hint about how their genetics interact with certain medications.
Testing can guide whether you need a higher or lower dose than the standard. For example, the FDA recommends that patients who are CYP2C19 poor metabolizers (based on genetic testing) take only half the typical dose of citalopram (Celexa) or a maximum of 20 mg per day, because their bodies clear the drug more slowly, and high levels could cause heart-related side effects.
Reducing Side Effects and Adverse Reactions: Genetics can make you more prone to specific side effects. Knowing this, we can choose a different medication, start at a safer dose, or avoid it altogether. This is especially useful for drugs with serious risks at high levels.
Case example: Tom had knee pain and didn’t like taking pain medication. But after trying everything, he applied a topical NSAID. Within 2 days, he developed a severe case of tinnitus. We took him off NSAID cream immediately, and following a PGx test, it revealed NSAIDs were to be avoided because of his genes. Tom now uses proteolytic enzymes, massage, and physical therapy to manage his pain.
Improving Efficacy: Some people break down a drug so fast that they get little benefit. In such cases, a higher dose or a different drug might be needed to get therapeutic effects. Pharmacogenomic testing flags these cases so you’re not left taking a medication that isn’t helping.
Pharmacogenomic testing is not yet available for every medication, and having a particular genotype doesn’t guarantee a specific outcome—it simply raises or lowers the probability of specific responses. We will use your genetic information alongside clinical judgment and factors like your overall health, other medications, and lifestyle.
How does this apply to specific drugs and genes?
Antidepressants and Your Genes: Citalopram, Paroxetine, and Fluoxetine
People who experience depression or anxiety are often prescribed a selective serotonin reuptake inhibitor (SSRI) such as citalopram (Celexa) or paroxetine (Paxil), and Fluoxetine (Prozac). But not everyone responds the same way.
Citalopram and CYP2C19: Citalopram is mainly broken down in the body by an enzyme called CYP2C19. Your CYP2C19 genotype can influence citalopram’s levels in your bloodstream. If you have a variant that makes CYP2C19 work poorly (i.e., you’re a CYP2C19 poor metabolizer), your body breaks down citalopram slowly. This can lead to higher drug levels, which might increase the risk of side effects such as drowsiness or even rare but serious effects like heart rhythm changes. The FDA recommends reduced doses for CYP2C19 poor metabolizers taking citalopram.
Clinical guidelines also suggest that if citalopram is used in a poor metabolizer, it should be at a lower dose with careful monitoring. On the other hand, if you have a genotype that makes CYP2C19 overly active (ultra-rapid metabolizer), you might eliminate citalopram too quickly. Such individuals may not get sufficient benefit because the drug doesn’t stay around long enough to work.
Paroxetine and CYP2D6: Paroxetine is primarily metabolized by a different enzyme, CYP2D6. Genetic variants of CYP2D6 are well-known to affect how people respond to certain antidepressants. If you are a CYP2D6 poor metabolizer, your body has difficulty breaking down paroxetine. This means drug levels can build up higher than expected, which increases the chance of side effects (for example, nausea, fatigue, or other side effects could be more pronounced). Because of this, one strategy is to use a lower dose or choose a different antidepressant not reliant on CYP2D6 for people with this genotype.
If you are a CYP2D6 ultra-rapid metabolizer, you clear paroxetine very quickly. The drug might not reach adequate levels, making it less likely to improve your symptoms. This is important because the same enzymes also metabolize many other antidepressants.
Fluoxetine (Prozac) is one of the oldest and most prescribed selective serotonin reuptake inhibitors (SSRIs). It’s used for depression, anxiety disorders, OCD, PMDD, and other mental health conditions. Genetics can significantly influence how your body handles fluoxetine, particularly through variations in the CYP2D6 enzyme.
Fluoxetine and CYP2D6 Poor Metabolizers: If genetic testing identifies you as a poor metabolizer of CYP2D6, fluoxetine and its active metabolite, norfluoxetine, will remain in your system much longer. This slower breakdown can lead to higher drug levels and increased risk of side effects such as nausea, jitteriness, insomnia, or emotional numbness. In such cases, your doctor may start with a lower dose or consider another SSRI that isn’t heavily dependent on CYP2D6 for metabolism.
Fluoxetine and CYP2D6 Rapid Metabolizers: For ultra-rapid metabolizers, fluoxetine may clear more rapidly, potentially reducing its effectiveness at standard doses. However, fluoxetine is unique because its active metabolite (norfluoxetine) has a long half-life. Therefore, rapid metabolism may not significantly impact fluoxetine efficacy compared to other SSRIs. Nevertheless, pharmacogenomic testing can help explain unexpected treatment responses and inform dosage adjustments or alternative treatment considerations.
Pain Medication and Your Genes: Codeine, Tramadol, and Morphine
Anyone who has dealt with pain management knows that we respond differently to pain medications called analgesics. Pharmacogenomics plays a significant role here, especially with certain opioids:
Codeine & Tramadol. Codeine and tramadol are both medications that need to be activated by the liver to relieve pain. They are considered “prodrugs.”
Codeine, for instance, is converted into morphine (its active form) by the enzyme CYP2D6
Tramadol is similarly converted into a more potent pain-relieving metabolite by CYP2D6. What happens if your CYP2D6 gene isn’t very active? If you are a CYP2D6 poor metabolizer, you have little or no functional CYP2D6 enzyme. Taking codeine in that case is likely to give you little relief, because your body can’t convert enough of it into morphine.
The same goes for tramadol – it may not work well if you can’t metabolize it effectively. On the flip side, if you’re a CYP2D6 ultra-rapid metabolizer with extra-active enzymes, you might convert codeine to morphine too well. This can be dangerous: even a standard dose of codeine could lead to unexpectedly high morphine levels in your body.
Such individuals can experience signs of morphine overdose, including extreme sleepiness, shallow breathing, and confusion at regular doses. There have been cases of children and adults suffering serious harm, and even fatalities, in these situations. For example, some ultra-rapid metabolizers who took codeine after surgery or mothers who took codeine while breastfeeding and passed morphine to infants through milk, experienced life-threatening effects.
Guidelines in action: Because of these risks and inefficacies, guidelines recommend avoiding codeine in anyone known to be a CYP2D6 ultra-rapid or poor metabolizer. If your genetic test shows either extreme, doctors will likely choose a different painkiller. In poor metabolizers, codeine or tramadol would be useless (no pain relief). In ultra-rapid metabolizers, they would be unsafe. Instead, physicians might prescribe other opioids that don’t depend on CYP2D6 – for instance, morphine itself, oxycodone, or hydromorphone – or non-opioid pain relievers as appropriate.
Morphine & OPRM1 – Your Opioid Receptors: Unlike codeine and tramadol, morphine is already in its active form when given. It doesn’t require CYP2D6 activation, so CYP2D6 genetic status isn’t a direct issue for morphine dosing. This is why morphine is often a go-to alternative for patients who have CYP2D6 variants that make codeine ineffective or unsafe.
However, another gene comes into play with drugs like morphine: OPRM1. This gene encodes the mu-opioid receptor, which is the primary receptor in your brain and body that opioids bind to to relieve pain. A well-studied variant of OPRM1 (often referred to as the A118G mutation, or the Asp40 variant) changes a single building block in the receptor. Research has shown that people who carry this variant can have a different experience of pain relief.
Some studies suggest that individuals with the OPRM1 Asp40 variant may have a higher tolerance to pain or require higher doses of opioids to achieve the same level of pain relief. In other words, their receptors might not respond as strongly to the typical opioid dose. This variant is also associated with differences in how people experience the effects of opioids and even alcohol (more on that shortly). In a pain management context, if a patient isn’t responding to morphine as expected, and they carry specific OPRM1 gene variants, a clinician might consider this information when adjusting the pain control strategy (for example, trying a different medication or dosage).
Pharmacogenomic testing can be instrumental in pain management. It can prevent someone from being given a drug that won’t work for them (saving time and pain) and avert dangerous situations by flagging those who might have severe reactions.
Pharmacogenomics in Addiction Treatment: Naltrexone
Pharmacogenomics is also helpful in personalizing addiction treatment: Naltrexone, a medication used to treat alcohol use disorder and opioid dependence. Naltrexone works by blocking opioid receptors, particularly the mu-opioid receptors coded by the OPRM1 gene. By blocking these receptors, naltrexone can reduce the pleasurable effects of alcohol or opioids and help prevent relapse.
Studies have found a notable pattern: individuals with the Asp40 variant of OPRM1 tend to have better outcomes when treated with naltrexone for alcohol dependence. In a large clinical trial, alcoholic patients carrying this genetic variant had significantly lower relapse rates on naltrexone compared to those without the variant, who didn’t seem to benefit as much from the medication.
Thus one’s genotype at the OPRM1 gene might predict how well naltrexone will work: carriers of the G (Asp40) allele often respond more favorably, experiencing reduced cravings and more extended periods of abstinence, whereas those with the “AA” genotype (no variant) might not see as strong an effect from naltrexone.
What does this mean for treatment? If you are struggling with alcohol use disorder, you might consider pharmacogenomic testing of the OPRM1 gene. If you have the OPRM1 Asp40 variant, it could strengthen the case for using naltrexone as part of the treatment plan, since the odds of success might be higher. Or if you do not carry that variant, naltrexone might be less effective, and you have other choices.
Not all doctors routinely test for OPRM1 variants yet, so you need to ask for the test or obtain it on your own.
Benzodiazepines: Diazepam, Alprazolam
Benzodiazepines, such as diazepam (Valium) and alprazolam (Xanax), are widely used for anxiety, panic attacks, insomnia, and muscle relaxation. Like other medications, your body’s response to benzodiazepines can be influenced by your genetics, particularly by enzymes called CYP450 enzymes. Aside from genetics, these drugs are highly addictive and are linked to cognitive decline when used long-term.
Diazepam: Diazepam is mainly metabolized by the CYP2C19 enzyme. If your genetic test identifies you as a poor metabolizer for CYP2C19, your body breaks down diazepam more slowly, increasing the risk of side effects such as prolonged sedation, dizziness, and impaired coordination. In such cases, doctors usually recommend a lower dose or choosing a benzodiazepine less affected by CYP2C19. Conversely, if you are a rapid or ultra-rapid metabolizer, diazepam may clear quickly, reducing effectiveness and possibly requiring higher or more frequent dosing.
Alprazolam. Alprazolam is primarily metabolized by the CYP3A4 enzyme, another essential enzyme sometimes included in pharmacogenomic tests. While variants in CYP3A4 aren’t commonly part of standard panels, medications or supplements that strongly inhibit or induce CYP3A4, such as grapefruit juice or certain antibiotics, can profoundly impact alprazolam levels.
How Is Pharmacogenomic Testing Done
The process of pharmacogenomic testing is valuable and straightforward:
- Sample Collection: You provide a DNA sample from a simple cheek swab or saliva sample, which you spit into a tube. Many clinicians suggest using a pseudonym to keep your results private and not associated with your name.
- Laboratory Analysis: A specialized genetics lab analyzes the sample, looking at specific genes and genetic variants. For a pharmacogenomic panel, this often includes genes like CYP2D6, CYP2C19, CYP2C9, SLCO1B1, TPMT, DPYD, UGT1A1, VKORC1, OPRM1, and others, depending on the panel and the medications of interest.
- Results and Interpretation: The report will list the gene variants you have and often will categorize your predicted enzyme function (e.g., “CYP2D6: Poor Metabolizer” or “CYP2C19: Normal Metabolizer”, etc). It may also directly mention impacted drugs – for instance, it might say that for codeine, you have “diminished analgesic response expected” or for citalopram, “use lower dose” based on your genotype.
Clinical Decision-Making: This information lets you and your provider make more informed choices. The test might guide the initial selection or dosing if you’re starting a medication. If you’re reviewing past medications, it might explain why some caused bad reactions or didn’t work, and help in planning future treatments.
Conclusion
Pharmacogenomic testing represents a significant step toward truly personalized medicine. By decoding the information in your genes, we can better predict which medications will be safest and most effective for you.
As research continues and more genes and drug interactions are understood, pharmacogenomic testing will likely become a routine part of healthcare. Sometimes insurance will cover the testing.
Labs that offer Mental Health, Pain, and Addiction Genomic testing
Stay tuned for Part 2, when I address how understanding the genes affects the herbal medicines you take!
Interested in helping your clients taper? Check out my 3-hour course.
References
St. Jude Children’s Research Hospital. Cytochrome P450 2C19 (CYP2C19) – Clinical Pharmacogenomics
Dean, L. (2025). Codeine therapy and CYP2D6 genotype. In M. P. Pratt, L. Dean, & M. K. Rubinstein (Eds.), Medical genetics summaries. National Center for Biotechnology Information (US). https://www.ncbi.nlm.nih.gov/books/NBK100662/
Clinical Pharmacogenetics Implementation Consortium (CPIC). Citalopram–CYP2C19 guideline annotation. (FDA recommendation for citalopram dose reduction in CYP2C19 poor metabolizers)
Anton, R. F., Oroszi, G., O’Malley, S., Couper, D., Swift, R., Pettinati, H., & Goldman, D. (2008). An evaluation of mu-opioid receptor (OPRM1) as a predictor of naltrexone response in the treatment of alcohol dependence: results from the Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence (COMBINE) study. Archives of general psychiatry, 65(2), 135–144. https://doi.org/10.1001/archpsyc.65.2.135
She served as a Fulbright scholar on traditional medicine, a Clinical Fellow at Harvard Medical School, and a National Institutes of Health-funded research scientist in mind/body medicine.
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