Genetic Defects Lead to High-Dose Opioids

Patients Needing High-Dose Opioids May Have Genetic Defects | Medpage Today | September 11, 2016 | by Molly Walker from Pain Week 2016

Chronic pain patients who require high-dose opioids seem to have genetic anomalies that impact their ability to metabolize drugs, researchers reported here.

In a small survey, 91% of patients taking opioids in excess of 100 morphine milligram equivalent (MME) per day had defects in cytochrome P450 enzymes, which are involved in drug metabolism.

This has been well known since at least 2012, so it seems quite outrageous that the CDC guidelines never took it into account in their supposed “scientific” guidelines. 

Establishing arbitrary dose limits without accounting for significant individual genetic differences shows a disregard for scientific facts and is a sad display of the lack of medical knowledge at the CDC. 

“Now everybody’s interested, because CDC regulations and state guidelines have established standard of care,” said Tennant. “Every pain practitioner, if they’re going to go [with a dose above 100 MME level should probably have their patients take genetic tests. This is a simple screen that is being offered by all genetic testing companies.”

“Genetic testing may allow us greater insight in to how these drugs behave in the bodies of individual patients, and may be able to explain why a subset of patients seem to require very high doses,”

“Exploiting genetic difference between patients may someday soon help us better target therapy so as to minimize risk to the patient while affording them optimal analgesia.”  

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6 thoughts on “Genetic Defects Lead to High-Dose Opioids

  1. humanecare

    This shows how the CDC blatantly disregarded this information. It was included in public comments when they took the 4,000+ comments. Many commented on this issue at that time. Cancer doctors have known about this since the early 2000’s. Now the new “suggested” limits from the CDC guidelines, are being misused by insurance companies to deny claims for medications over the CDC limit, and medical boards are harassing doctors who prescribe over the exalted “standard of care.” Expensive procedures and devices are generally approved, which can often cause more harm than simple medications. Epidural injections are a temporary and expensive means of pain control. We don’t know what the long term effect down the road is for patients who have been exposed multiple times. We do know that adhesive arachnoiditis is one of the devastating side effects of these injections. When these procedures go wrong, the patient is often left with nowhere to turn.

    A huge piece missing from the public conversation is the scientific fact that:
    Approximately one third of the population has proven genetic anomalies of the Cytochrome P450 enzymatic pathway which metabolizes 25 percent of all drugs including the most standard opioids that are commonly prescribed. Those 30 percent of pain patients were ignored completely during the drafting of these CDC guidelines. Genetic defects of this metabolic pathway can cause many commonly used analgesics to be useless for some of these patients, unless they are prescribed in a higher dose than what the guidelines recommends. Non-standard analgesics often need to be utilized with these individuals. Approximately 7% percent of the North American population has an anomaly of the CYP2D6 pathway, called Ultra Rapid Metabolizing. This is one group where most standard medications for analgesia do not work. There are many other anomalies of Cytochrome p450 which were not even mentioned in the CDC guidelines. When all these differences are combined we are talking about approximately 30% of patients that have a unique non-standard reaction to many classes and types of medications, including opioids. This is a significant number of patients who have been effectively left out of the conversation. To ignore this basic science is to deprive 30 percent of the population adequate analgesia from the ER, post surgery and in treating chronic pain. For insurance to tag the doctors who prescribe for these patients “over-prescribers” without the basic understanding of the latest science of pharmacogenomics, is discriminatory and immoral. The CDC guidelines are not up to date with the latest scientific information on genetics and the effects individual metabolism has on many types of medications. What are these patients and their doctors to do? These people are often tagged as addicts, drug seekers or as having a tolerance when they simple have a “fault in their genes.

    One size medicine doesn’t fit all! Where is “precision medicine” when it comes to analgesia?

    These medically complex patients and their physicians are not the cause of the “prescription drug abuse and overdose epidemic.” Legitimate pain patients who have been thoroughly screened and monitored closely by their physicians should not be subject to undo suffering because of an addiction crisis of non-medical use of opioids.

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    1. Zyp Czyk Post author

      Wow, this situation is worse than I thought. I suspect I’m a slow metabolizer, since it can take up to 3 hours for pain meds to work, but then the relief lasts a very long time.

      I don’t understand how the government can be spending millions on genetically based precision medicine to take into account individual differences and at the same time, creating guidelines that completely ignore these differences and spending millions on the drug-war that targets such individuals when they need high opioid doses.

      Hundreds of millions of dollars are being spent on both initiatives by the same entity, even though they contradict each other. Some day in the future, this will be recognized as a shameful period of torturing medically disadvantaged and disabled people.

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  2. humanecare

    Yes, it is contradictory. I did write to the Precision Medicine Initiative a couple years back when it was announced out to make sure they included this information when looking at pain medication. I didn’t hear anything back.
    The University of Washington doctors, who were contracted to teach the guidelines to doctors for the CDC are really out of step with the times, to not include pharmacogenetics in their information. Of course they are also PROP members, so there you have it.
    It is discriminatory as it was blatantly ignored.

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    1. Zyp Czyk Post author

      This is so sad. The anti-scientific views being codified these days will eventually be seen as the joke they are, but until then what are we supposed to do? I’m so glad I live in one of the more progressive states (CA) where there’s less of this nonsense than on the east coast.

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