My primary focus is on U.S. and international public health policy for treatment of severe chronic pain. I have been active for over 28 years as a health care writer and educator, with over 300 papers authored or co-authored in a mix of peer-reviewed journals and mass media.
I am a particular critic of what I believe to be the proven misdirection (a.k.a. “fraud“) committed by Federal and State health care authorities concerning pain treatment that employs prescription opioid analgesics. However, I base my published work on data; not opinions of my own or anyone else’s.
I have deeply explored data published by the U.S. CDC, FDA, NIDA, NIH, and Veterans Administration concerning addiction, hospital admissions, and accidental deaths involving prescription opioids. I have also read widely in the literature of pain management, under the guidance of highly experienced, board-certified clinicians who treat pain, some of whom have co-authored papers with me.
From this background, I offer two papers that may help improve understanding of the science of pain management among clinicians of all kinds who treat pain: “Opioids and Chronic Pain: An Analytic Review of the Clinical Evidence” and “Opioid trials: Time for a new approach? Enriched enrollment randomized gradual withdrawal designs.”
The first of these papers is a wide-ranging analytical literature review for the effectiveness and safety of prescription opioid analgesics. Among other findings, the paper identifies a 15-to-1 range in minimum effective opioid dose levels between individual patients, depending on which cited source one believes.
The second paper identifies one of the primary causes of this wide range. Metabolism of opioids into metabolites that can cross the blood-brain barrier is mediated by CYP-450 series enzymes in the human liver. Because of natural genetic polymorphism between individuals, (1) some people are “poor” metabolizers, (2) some are “average” metabolizers, and (3) some are “hyper” metabolizers.
An estimated 20-30 percent of pain patients fall into category 1 or category 3 above. To provide adequate pain control, poor opioid metabolizers may need many times the opioid dose levels recommended by FDA for average metabolizers. The same is also true for “hyper” metabolizers. Among these two categories of patients, some can benefit from dose levels measured not in milligrams per day, but in GRAMS per day. Such patients can tolerate dose levels that would knock over a horse. For poor metabolizers, blood concentrations of metabolites do not reach effective levels; for hyper-metabolizers, metabolites leave the body very rapidly, obviating drug overdose dangers.
There is a horrifying corollary to this finding: Genomic effects in individuals were omitted from the 2016 and 2023 opioid prescribing guidelines of the U.S. Centers for Disease Control and in derivative guidelines of the U.S. Veterans Administration. Indeed, there is evidence that this deliberate omission was known by guideline authors and reviewing officials before publication.
Both CDC and VA opioid prescribing guidelines completely omit mention of the effects of individual opioid metabolism on clinical prescribing practice. Authors chose instead to advocate (without citing literature references) for a fictitious maximum “threshold” (90 morphine milligram equivalent daily dose), beyond which opioids were asserted to have diminishing effects in pain control.
Such errors would be sufficiently alarming if they pertained only to the practice of pain medicine. However, about 50-60 percent of prescription drugs that undergo metabolism are metabolized in the human liver. Specifically, the liver’s cytochrome P450 enzyme system is responsible for metabolizing nearly half or more of all clinically relevant medications. This is science well known to almost any clinician who practices in pain medicine.
An estimated 250,000 to 300,000 deaths occur each year in the U.S. due to adverse drug events (ADEs). These deaths include medication errors, overdoses, drug interactions, and allergic reactions in hospitals and other health care settings. ADEs are now considered the third leading cause of death in the U.S., surpassing deaths from stroke and respiratory diseases. Medication errors alone are estimated to cause between 44,000 to 98,000 hospital deaths annually.
Clinicians generally do not consider these death rates to be precise because of the many contributing factors in mortality. However, it seems appropriate to ask whether some adverse drug events result not from drug reactions, but rather from lack of titration, or over- or under-prescription of drugs to individuals who have unusually slow or fast metabolism.
Only a small percentage of all drug trials have attempted to address the natural variability of metabolism between trials subjects. This reality renders FDA dose recommendations highly suspect. It also suggests that U.S. pharmaceutical manufacturers and the National Institutes of Health may soon face requirements for Billions of dollars of new investment in drug trials, at a time when financial resources are sharply limited.
Precision pain protocols
In addition to these investments, “Precision Pain Protocols” must become the near-term standard of practice for pain management.
- Such protocols: Integrate pharmacogenomics screening into routine care, subsidized by the Centers for Medicare and Medicaid (CMS), to flag metabolizer status and guide dosing. Such protocols directly address ADE root causes and guideline flaws.
- Second: We must promote clinician autonomy via “safe harbor” rules protecting physicians from liability for evidence-based deviations from thresholds, when documented with patient data and observations.
- Third: We must halt the ongoing CMS code purge; instead, fund hybrid models blending procedures, low-risk opioids, and trials like those proposed above for gradual withdrawal.
It is amazing how often even the best clinicians relearn that “the more things change, the more they are the same.” In this instance, we may be rediscovering that the World Health Organization (WHO) 1986 “Analgesic Ladder” offers far better guidance than more recent prescribing guidelines of the CDC and VA. This ladder proposes:
- Start pain treatment with non-opioid medications unless pain is sufficiently intense or patient sensitivity to NSAIDs renders them contraindicated.
- If non-opioids are insufficient, then add or change to weak opioids; titrate dose upward until effective levels are found or unacceptable side effects occur.
- If weak opioids are insufficient, then add or change to stronger opioids; start at low doses and titrate to desired effect, actively managing side effects.
- At all levels of the ladder, non-pharmaceutical adjuncts may be added to provide patient support, but not as a substitute for pharmaceutical treatment.
- Monitor for and treat depression and anxiety that may compromise patient welfare and therapy effectiveness.
Richard A. Lawhernis a nationally recognized health care educator and patient advocate who has spent nearly three decades researching pain management and addiction policy. His extensive body of work, including over 300 published papers and interviews, reflects a deep critique of U.S. health care agencies and their approaches to chronic pain treatment. Now retired from formal academic and hospital affiliations, Richard continues to engage with professional and public audiences through platforms such asLinkedIn,Facebook, and his contributions toKevinMD. His advocacy extends to online communities likeProtect People in Pain, where he works to elevate the voices of patients navigating restrictive opioid policies. Among his many publications is a guideline onopioid use for chronic non-cancer pain, reflecting his commitment to evidence-based reform in pain medicine.