Pharmacogenetics - genetic testing can help predict which drugs will have more side effects or be ineffective

Researchers have been discovering that your genetics affect how your body metabolizes a drug. For a few drugs, your genetics can have dangerous interactions with drugs or cause them to be less effective than you’d like them to be.

For chronic illness, your genes are relevant if you may try these drugs in the future:

  • Pain meds like opiates, codeine, SSRIs, TCAs
  • Anti-depressants, anti-anxiety drugs
  • Benzos / benzodiazepines, i.e. for MCAS, anxiety, or sleep
  • Phenytoin
  • Clopidogrel, one of the drugs in triple anticoag therapy

Why genetic testing isn’t popular right now

  1. There’s not a lot of money to be made because it doesn’t help pharma sell drugs.
  2. Your genes don’t matter for most drugs. Or, researchers haven’t yet figured out how the genes are relevant.
  3. It was expensive in the past. (*The cost is coming down rapidly, similar to how computers have come down in price.)

However, in chronic illness patients, genetic testing may be more useful because patients try so many different drugs.

List of genetic interactions with drugs

Drugs where pharmacogenetcs is very useful Highlighted uses Gene variant Useful?
Opioids e.g. Codeine (prodrug) Pain CYP2D6 Can be dangerous (to the patient or a breast-fed baby) with ultra-metabolizer genes. See
Paroxetine, Sertraline, SSRIs Anxiety, depression CYP2D6, CYP2C19 Extensive literature indicates that patients with specific genetic differences in the CYP2D6 gene may require dose adjustments of paroxetine or an alternative medication in order to achieve therapeutic benefits or to avoid side effects. Paroxetine (Paxil)- CYP2D6 – MyDrugGenome
TCAs - Amitriptyline
Pain, anxiety, depression, insomnia CYP2D6, CYP2C19 Some genes are associated with treatment failure or increased side effects. See PharmGKB for amitriptyline.
Benzodiazepines, e.g. Diazepam sleep, anxiety, MCAS CYP2C19 Recent studies evaluating the clinical impact of the CYP2C19 gene on diazepam for AWS have identified that individuals with reduced CYP2C19 activity may be at increased risk of adverse effects whereas those with increased CYP2C19 activity may experience reduced efficacy with standard doses of diazepam. JPM | Free Full-Text | Clinical Impact of the CYP2C19 Gene on Diazepam for the Management of Alcohol Withdrawal Syndrome
Phenytoin (Dilantin) anticonvulsant CYP2C9, CYP2C19 Gene variants can result in toxicity
Clopidogrel Anticoag CYP1A2 Sometimes, in people who need anticoag for other reasons
Drugs where pharmacogenetcs is less useful Highlighted uses Gene variant Useful?
Abilify / Aripiprazole anti-psychotic CYP2D6 Poor metabolizers can be accidentally overdosed and experience side effects; may be less of an issue when starting with very low dosages for low-dose Abilify. see Aripiprazole Therapy and CYP2D6 Genotype - Medical Genetics Summaries - NCBI Bookshelf
Ibuprofen, a few other NSAIDs pain CYP2C9 Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C9 and Nonsteroidal Anti-inflammatory Drugs - PMC
Metoprolol beta blocker CYP2D6 FDA does not specifically comment on the role of genetic testing for initiating therapy.
see Metoprolol Therapy and CYP2D6 Genotype - Medical Genetics Summaries - NCBI Bookshelf
Naltrexone (low dose) Chronic illness ??? Pharmacogenetics of Naltrexone in Asian Americans: A Randomized Placebo-Controlled Laboratory Study | Neuropsychopharmacology
Pravastatin, Simvastatin Lowering cholesterol SLCO1B1 SLCO1B1 variant increases chance of myopathy (muscle weakness)

Where to get medical expertise

This stuff is complicated because scientists are learning more and more about how obscure genes work.

You can hire a Genetic Counsellor (or a clinical geneticist) offering pharmacogenetics services to help you navigate this world.

I don’t see pharmacogenetics being popular in chronic illness

If you’ve had chronic illness for a while, you’ve probably already tried most of the drugs. So it’s too late for genetic testing to have a benefit.

If you’re new to chronic illness, you’re probably way too wrapped up in other things to have the time to figure out pharmacogenetcs. It doesn’t solve any of your immediate problems.

If the medical system was better, then doctors would quickly recognize how debilitating your health problems are. That would let them anticipate the long list of drugs that you will try in the future. Insurance would cover the cost of the genetic testing and the services of a genetic counselor before you try many drugs in the quest to find something that helps. In practice, I don’t see that happening anytime soon. While this test would help spot dangerous drugs, most people will not get genetic testing before they are put on that drug.

This is a high-tech area of medicine that requires genetic counselors with a master’s degree. However, chronic illness patients likely won’t benefit (mildly) from this innovation because there isn’t much money to be made.