Genetic testing for methadone metabolism





Genomic medicine is growing quickly. This is a branch of medicine that studies an individual’s genetic profile in order to be able to predict which medications may work best. This information can also predict if a patient will have a problem with a specific medication.

Some people have genes that make them slow metabolizers of methadone. This is a particular problem, since methadone is such a long-acting drug. Slow metabolizers are at increased risk of methadone accumulation, leading to over -sedation and overdose death. If we had a way to identify slow metabolizers, perhaps we could prevent these deaths, by starting them at lower methadone doses.

Researchers at Washington University in St Louis have discovered genetic subtypes that are associated with both faster methadone metabolism and slower methadone metabolism.

Researchers took blood samples from normal volunteers for genetic testing, and then gave these test subjects doses of methadone. As expected, these people metabolized methadone at markedly different rates. So far, that’s not news. We’ve known for years that people metabolize methadone at very different rates. But this study showed what genetic variants influenced the rate of methadone clearance. Two genetic subtypes for the gene for cytochrome P2B6 were found; one increased the metabolism of methadone and the other resulted in slower-than-usual metabolism of methadone.

Interestingly, the researchers found that African-American people were more likely to have the subtype of this gene giving slower methadone clearance. These patients may be at increased risk for overdose, if given the same dose as patients with the genetic subtype resulting in faster methadone metabolism.

To the best of my knowledge, it’s not yet practical to get genetic testing done on a patient before I start methadone. Specialty labs do offer the testing, but my patients could not pay for it, unless it was paid for by insurance, including Medicaid.

Even after I get the information, how would I use it? For sure, if a patient had the genetic makeup of a slow metabolizer, I would start at a lower dose and increase more slowly. But I have no studies to guide me – I would be using my best clinical judgment.

What about a patient with the genetic makeup of a fast metabolizer? Would I feel comfortable starting at a higher dose and increasing that dose more quickly?

No, I would not. Perhaps that patient has a lower risk of overdose, perhaps not. Again, I have no studies that tell me for this certain gene, start at “x” dose. I don’t know that we will ever have that sort of specific information, since factors other than genetics must be considered.

I hope in the future I’ll see a role for genetic testing for patients starting medication-assisted treatment of opioid addiction. However, we would need studies showing how we can use the information. For now, the expense, turn-around time of testing, and lack of real-life studies using genetic information make genetic testing unworkable.

7 responses to this post.

  1. Posted by nspunx4 on December 18, 2015 at 6:27 pm

    I thought cpy450 (or four something 465?) was most responsible for absorption of methadone?


  2. Posted by Dr. Jack McCarthy on December 23, 2015 at 4:28 am

    Then you have the special issue of methadone metabolism in pregnancy where even a slow metabolizer can be converted to a rapid metabolizer by the induction of cytochrome enzymes. this makes methadone a short acting drug in pregnancy and dictated divided doses to avoid maternal and fetal withdrawal. We’ve been looking at the ratio of methadone to metabolite in pregnant patients and seen dramatic lowering of the ratio during pregnancy and reversal after delivery. It is clear that methadone has been dosed wrong in pregnancy for decades, including in the MOTHER study.

    These genetic studies are important, but measuring actual methadone and metabolite ratios are more important to the pregnant patient.

    Dr. Jack McCarthy


  3. Posted by kevin on December 25, 2015 at 9:51 pm

    Just wondering your thoughts about the way Tennessee is and the way a doctor has to ask someone that isn’t even a doctor permission to raise a patient over 120mg, do you think once this study is over and if it shows medical knowledge on this, do you think this could change the way they do things? It would be nice to finally get something through these people’s heads. It’s ridiculous the way they think they know more. I mean isn’t that why doctors go to school for years.


  4. Posted by Pane, Ed on December 29, 2015 at 2:45 pm

    Hello Dr.

    As this year draws to a close I just wanted to say how much I enjoy your Blog posts. I have learned much and given much to reflect on as well.

    Thank you for your contributions. I wish you a prosperous and joyful New Year.

    Ed Pane

    Edward A. Pane, LCSW, CAADC
    Catholic Social Services
    33 East Northampton Street
    Wilkes-Barre, PA 18701
    570-829-3489, ext 334


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