Posts Tagged ‘genetic testing for methadone metabolism’

Genetic testing for methadone metabolism

aaaaaaaaaaaaaaagenes

 

 

 

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.