Comments on California Opioid Guidelines - To the State Medical Board

Comments on Draft California Prescribing Guidelines

Richard A Lawhern PhD and Stephen E Nadeau MD

June 2022

These joint comments are offered in response to a circulated invitation to attend an Interested Parties Meeting on July 14, 2022.?

Richard Lawhern is a healthcare writer and non-physician subject matter expert on public policy for the regulation of opioid pain relievers and clinicians who employ them in managing severe chronic pain. He has 26 years’ experience as a patient advocate and forum moderator for online chronic pain communities, with over 150 published papers, articles and interviews in a mixture of mainstream medical journals,?mass media, and Internet podcast venues.

Stephen E Nadeau MD has been a member of the faculty of the University of Florida College of Medicine since 1987, providing clinical care, teaching residents and medical students, and pursuing research, primarily in behavioral neurology, neuroplasticity, and neurorehabilitation.??Since 2013, he has been Associate Chief of Staff for Research at Malcom Randal BA Medical Center.?Opinions expressed in this paper may not reflect positions of the US Veterans Administration.

A General Observation:

The term “risks” appears no less than 30 times in this 26-page document, and is frequently referenced to the 2016 CDC opioid guidelines.?Unfortunately, many uses of the term in this document are largely not germane to actual medical practice.?

The rising tide of opioid-associated deaths overwhelmingly reflects unsupervised use of opioids obtained on the illicit market, not exposure to prescribed analgesics.?The underlying assumption of this draft guideline seems to be the idea -- never expressly stated -- that any patient prescribed opioids in the context of good care, and presently cognitively sharp and fully conversational, might be in imminent danger of keeling over any minute in respiratory failure.?This construction is patently ludicrous.

Moreover, nowhere do we see an admission in this document that is deeply buried a pending 2022 update to the CDC guidelines:

“The clinical evidence reviews found no instrument with high accuracy for predicting opioid related harms such as overdose or opioid use disorder (Chou et al., April 2020). It can be very challenging for clinicians to predict whether benefits of opioids for chronic pain will outweigh risks of ongoing treatment for individual patients. Therefore, opioid therapy should not be initiated without consideration by the clinician and patient of an “exit strategy” that could be used if opioid therapy is unsuccessful.”?

The notion that clinicians must carefully evaluate individual patient risks versus benefits at every turn may reasonably be characterized as an oxymoron, in the absence of any reliable instrument for doing so in a defensible manner.?This conflict between reality versus theory must inevitably exercise a powerful suppressing effect on the willingness of clinicians to risk sanctions or law enforcement persecution in order to treat their patients.?

From this background, we must suggest that the emphasis on risk in the California Prescribing Guidelines is grossly over-hyped, reflecting many fundamental and fatal flaws in the CDC document to which it is closely related.?

We offer three deeply researched references in evidence of this misdirection as it occurs in the California guidelines.?

??Atch 1:?“Richard A Lawhern, “Comments on “CDC Clinical Practice Guideline for Prescribing Opioids–United States, 2022” [Submission to the US Federal Register, March 2022]

?Ref 2:?Stephen E Nadeau MD, Jeffrey K Wu, and Richard A Lawhern, Ph.D. “Opioids and Chronic Pain -- An Analytic Review of the Clinical Literature”,?Frontiers in Pain Research, ?August 17, 2021, Front. Pain Res., 17 August 2021, Citation https://doi.org/10.3389/fpain.2021.721357??https://www.frontiersin.org/articles/10.3389/fpain.2021.721357/full

?Ref 3:?Stephen E Nadeau, MD, and Richard A Lawhern, PhD. “Management of Chronic Non-Cancer Pain – A Framework”,?Future Medicine (Pain Management)?June 1, 2022, https://www.futuremedicine.com/doi/pdf/10.2217/pmt-2022-0017

We urge that unless the California guidelines are to be outright repudiated and withdrawn, this draft should be withdrawn for an independent “red team review” and significant rewriting before publication.?We also urge the insertion of explicit literature references for each of the claims of fact made in the guidelines.?

========= Specific Comments by Section =====

Preamble:

The California guideline characterizes the goal of the 2016 CDC Guidelines as “to ensure that clinicians considered safer and more effective pain treatment in order to improve patient outcomes (i.e. reduced pain and improved function) as well as to reduce the number of patients who developed opioid use disorder, overdose, or experienced other opioid-related adverse events.”?

With the advantage of hindsight, clinicians now know that the CDC guidelines had no such effect – and could never have had such an effect, given that the so-called “opioid crisis” was not an outcome of over-prescribing by clinicians to legitimate pain patients in the first place.?Data published by the US CDC itself reveals startlingly contradictory trends.?

It is known, for instance, that seniors age 65 and over are prescribed opioids about 60% more often than young adults age 25-34. This is a natural outcome of the accumulation of chronic pain conditions over patient lifetimes.?However, we also know that opioid-overdose-related mortality is currently 400% higher in young adults than in seniors, and is dominated by self-administered poly-drug exposure including alcohol and illicit street drugs.?

See Figure I and Figure 2 below, both extracted from CDC/SAMSA source data:

Figure 1:?Prescribing Rates by Age Cohort

Figure 2:?Overdose Related Mortality by Age and Year, 2001- 2020

In view of the data in these figures, it is simply impossible to reliably attribute opioid overdose mortality to medical treatment of the most frequently encountered patients.?The phenomena of addiction are far more complex than a purely “brain disease” model can account for.

Recommended Practices:

This section states that

“Physicians who treat patients with chronic pain should be encouraged to also be knowledgeable about the treatment of addiction, including the role of medication assisted therapy such as methadone and buprenorphine. For some physicians, there may be advantages to becoming eligible to treat opioid use disorder using office-based buprenorphine treatment. Referral to a pain medicine specialist or addiction medicine specialist prior to initiation of opioid therapy in high-risk patients may be considered as part of a risk mitigation strategy.”

Authors’ Observations:?the practice of pain management in chronic patients is highly complex and time consuming.?Treatment of chronic pain requires extensive education and experience, even as there is presently an incredible paucity of such training. [Ref 3A]????

Conditions of practice in addiction treatment are equally challenging.?It is a fundamental error to presume that patients can simply be put on Buprenorphrin or Methadone (even as useful as these medications are) without also examining the many psycho-social-economic issues that frequently surround addiction – e.g. mental health issues, poor education, ?unemployment, homelessness, co-morbid alcoholism etc.?Thus the practicality of dual practice in pain management and addiction treatment is highly debatable.??

In too many cases, specialists in both of these fields have been driven out of practice by excessively zealous regulation and law enforcement.?Thus it may be necessary for the State Medical Board to advocate for a funded long-term and multi-dimensional program to bring clinicians back into both fields, and to “grow” the numbers of interns and Residents who initially choose these fields of specialty.?Failing such initiatives, the current severe doctor shortage will only worsen, resulting in even more patient desertions.

?Ref 3A:?Shipton EE, Bate F, Garrick R, Skeketee C, Shipton EA, Visser EJ. “Systematic review of pain medicine content, teaching, and assessment in medical school curricula internationally.” ?Pain Therapy. 2018;7:139-61.

Exploring Non-Opioid Options:

This section includes the following:

“Opioid medications should not be the first line of treatment for a patient with chronic non- cancer pain. Other measures, such as non-opioid analgesics, non-steroidal anti- inflammatory drugs (NSAIDs), antidepressants, antiepileptic drugs, and non- pharmacologic therapies (e.g., physical therapy, pain psychology, nerve block, joint injections), should be tried and the outcomes of those therapies documented first. Opioid therapy should be considered only when other potentially safer and more effective therapies have proven inadequate. Determining if potential benefits of opioid analgesics outweigh the potential risks is key.”

Authors’ Observations:?While each of the named pain therapies may have a role in long term treatment of chronic pain, there is little or no clinical evidence that they are “preferable” when pain is severe.?NSAIDs at high doses have their own hazards in hundreds of yearly hospital admissions for intestinal bleeding and toxic liver reactions.?Anti-epileptic drugs and anti-depressants have limited applicability in neuropathic pain, and often cease to provide pain relief after months or years of success.?Physical therapy is often impossible for patients until their pain is at least partially controlled by other means.?Pain psychology has never undergone trials as a substitute for opioids.?

As mentioned previously, there are no reliable patient profiling instruments for assessing?individual risks of negative outcomes. ?Thus non-opioid pain therapies are presently best characterized as initial therapy for light to moderate pain, but may not be practical as primary long -term therapy in severe pain. ?They are most certainly not “replacements” or in any demonstrated sense “preferable” to opioids.

?Ref 4: Richard A Lawhern and Stephen E Nadeau, “Behind the AHRQ Report -- Understanding the limitations of “non-pharmacological, non-invasive” therapies for chronic pain.” Practical Pain Management, Vol 18 #7, October 3, 2018, https://www.practicalpainmanagement.com/resources/practice-management/behind-ahrq-report

Also of concern in this section is that there is at least a fifteen-to-one variation in minimum effective opioid dose, as reported in medical literature.?A significant part of this variability may be due to natural genetic polymorphism in expression of six key liver enzymes that govern metabolism of many medications in the liver. [op sit Ref 3]. Tellingly, the draft California Guideline document fails even to mention the terms “genetic” or “genomic”.?This omission must be constructively addressed in detail.

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Morphine Milligram Equivalent Dose

Authors’ Observations:?The Opioid Workgroup of the Board of Scientific Advisors to the US National Centers for Injury Prevention and Control has directly challenged the 50/90 MMED thresholds of both the 2016 CDC guidelines and proposed revised and expanded 2022 draft guidelines, as lacking any scientific basis.??No less an authority than the American Medical Association has also publicly stated that many patients are well served by opioid dose levels exceeding 90 MMED. [Ref 6]?There are case reports of a few patients who function well on doses exceeding 2,000 MMED, without impairment of cognitive function and with significant improvements in quality of life.

In the authors’ view, the concept of “Morphine Milligram Equivalence” is unsupported in the medical literature, and may properly be characterized as junk science.?[Ref 4A].?

All references to numerical MME dose thresholds or treatment time limits must be removed from the California Guidelines.?This action is also consistent with the most recent edition of opioid guidelines issued by the Federation of State Medical Boards.?

To the extent that California law levies MME limits on medical practice, such laws must be repealed as destructive to the practice of medicine and the welfare of patients, and the California Guideline should explicitly advocate to this effect.

?Ref 4A:??Jeffrey Fudin, ?Jacqueline Pratt Cleary,?Michael E Schatman ?“The MEDD myth: the impact of pseudoscience on pain research and prescribing-guideline development”, ?Journal of Pain Research, ?March 4, 2016, ??https://www.dovepress.com/the-medd-myth-the-impact-of-pseudoscience-on-pain-research-and-prescri-peer-reviewed-fulltext-article-JPR

?Ref 5: Dr Chinzano Cunningham, “Observations of the Opioid Workgroup of the Board of Scientific Counselors of the National Center for Injury Prevention and Control on the Updated CDC Guideline for Prescribing Opioids”, July 16, 2021 https://www.cdc.gov/injury/pdfs/bsc/Observations-on-the-Updated-CDC-Guideline-for-Prescribing-6-30-2021-508.pdf

?Ref 6:?Interim Meeting of the House of Delegates, American Medical Association, “Resolution 235, -- Inappropriate Use of CDC?Guidelines for Prescribing Opioids” November 13, 2018.

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Counseling Patients on Overdose Risk and Response

This section of the California Guidelines mandates offering prescriptions of Naloxone to any patient receiving more than 90 MME per day of an opioid medication.

Authors’ Observations:?As noted previously, the 90 MME per day threshold proposed in this section is arbitrary and unsupported by trials data of any kind.?Likewise, while Naloxone has been used effectively as an intervention by first responders with addicted (often socially isolated) persons who overdose on illegal street drugs, there is no body of evidence that even remotely supports general utility of this intervention in pain patients who are under active medical oversight, and who have support from co-resident family members. At least one controlled randomized trial in a clinical pain population failed to reveal any benefit.

??Ref 6A:?Banta-Green C, Coffin PO, Merrill JO et al. “Impacts of an opioid overdose prevention intervention delivered subsequent to acute care.” Injury Prevention. 25(3), 191–198 (2019).

Although many persons with addiction suffer from chronic pain, the opposite is rarely the case.?Emergence of substance abuse or addiction in medically managed patients is in fact rare even in patients assessed to have background factors associated with increased risk of substance abuse. [Ref 7] ?

The typical chronic pain patient is a female in her 40’s or older.?If her life is stable enough to allow her to see a physician regularly, she is very unlikely to suffer from a substance use disorder.?However, the typical addict is a young adult male with a high school education, a history of unemployment and mental health issues, and possibly involvement with law enforcement.?It is well known that this population is medically under-served.?

Incidence of prescription opioid overdose in medical patients appears to be on the order of 0.25% to 0.5% per year – too small to reliably identify any sub-group of patients under treatment which may actually benefit from such prescriptions.??[op cit Ref 2 and Ref 6B]

?Ref 6B: ?Bohnert ASB, Valenstein M, Bair MJ, Ganoczy D, McCarthy JF, Ilgen MA, et al. “Association between opioid prescribing patterns and opioid overdose-related deaths. JAMA. (2011) 305:1315–21. doi: 10.1001/jama.2011.370”

?Ref 7: ??Nora D Volkow, MD, and Thomas A McLellan, Ph.D., “Opioid Abuse in Chronic Pain — Misconceptions and Mitigation Strategies” .?NEMJ 2016; 374:1253-1263 March 31, 2016].?https://www.nejm.org/doi/full/10.1056/NEJMra1507771

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Ongoing Patient Assessment

Authors’ Observations:?The medical literature offers no hard data on benefits of urine testing for patients themselves. [op cit, Ref 2, Ref 3]?Many clinicians are also not appropriately trained on interpretation of urine test results, and many insurance plans do not reimburse for such testing. [Ref 8] Arguably the only real reason for such testing is to provide the doctor with an excuse for discharging non-compliant patients – a practice profoundly not in the patient’s best interests and potentially comprising patient desertion.

Ongoing patient assessment is clearly appropriate and needed -- but not for the reasons or following from the logic offered in this draft guideline.

?Ref 8: ?Utsha G Katri and Shoshana V Aronovitz “Considering the harms of our habits: The reflexive urine drug screen in opioid use disorder treatment”?Journal of Substance Abuse Treatment, April 2021.?https://doi.org/10.1016/j.jsat.2020.108258

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Compliance Monitoring

Authors’ Observations:?There are no hard data in medical literature to establish patient benefits from treatment contracts [Ref 8A].?The real motivation behind this section is quite obvious:?to provide excuses for patient discharge or involuntary tapering – both of which are associated with significantly increased incidence of medical crisis and/or patient overdose mortality. [Ref 9]

This section of the California Guidelines must be rewritten to make clear that patient drug-seeking behavior is in fact rare. Greater focus is needed on assessing blood plasma levels of prodrugs (metabolic products) generated by opioid therapy, as an aid to adjusting dose levels to the metabolism of the individual patient.

?Ref 8A:?Roger Chriss, “Little Evidence that Pain Contracts Work”,?Pain News Network, March 21, 2017.??https://www.painnewsnetwork.org/stories/2017/3/21/little-evidence-that-pain-contracts-work

?Ref 9:?Alicia Agnoli? ,?Guibo Xing? ,?Daniel J Tancredi? , et al:?“Association of Dose Tapering With Overdose or Mental Health Crisis Among Patients Prescribed Long-term Opioids”??Journal of the American Medical Association, August 3, 2021, doi: 10.1001/jama.2021.11013 https://pubmed.ncbi.nlm.nih.gov/34342618/

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CURES Reports also Urine Drug Testing

Authors’ Observations:?Law enforcement access to the CURES database must be conditioned upon issuance of a court warrant establishing that there is probable cause to believe a crime has been committed.?Nineteen other US States have already taken action to guarantee such legal due process for clinicians and their patients. [Ref 10] ?The California Medical Board should explicitly endorse this change to California law in its opioid guidelines.?Likewise, remove reference to CDC “fact sheets” on this subject, as the CDC material is riddled with errors and anti-opioid bias.?

[Ref 10]:?Jeffrey A Singer, “Arizona Becomes 19th State to Ban Warrantless Searches of Prescription Drug Database”?Cato At Liberty, June 16, 2022.?https://www.cato.org/blog/arizona-becomes-19th-state-ban-warrantless-searches-prescription-drug-database?

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Pill Counting

Authors’ Observations:?The practice of pill counting is enormously destructive to the clinician-patient relationship, communicating an undeserved distrust in the patient’s veracity and good will.?If the patient is already being seen monthly in person or by video conference, then pill diversion will readily become apparent from the patient’s repeated narratives of accidental loss or theft.

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Discontinuing Opioid Therapy

This section includes the following wording:

“Patients with unanticipated challenges to tapering, such as inability to make progress in tapering despite opioid-related harm, might have undiagnosed opioid use disorder.”

Authors’ Observations:?It is far more likely that patient challenges are a consequence of uncontrolled breakthrough pain, possibly complicated by clinician predispositions to misinterpret their distress and depression as “drug seeking behavior”.?This phenomenon is properly referred to as “pseudo addiction” and should be explicitly discussed as such in this section of the California guidelines.?

While referral for co-treatment of drug addiction or substance use disorder is sometimes appropriate in a small cohort of patients, a decision to terminate care for chronic pain solely for the protection of the clinician from censure is never under any circumstances medically ethical.

??[Op cit, Ref 2]

?Special Patient Populations

This section of the California Guidelines identifies populations in which the Guidelines may not apply.?Specifically excluded are acute pain, cancer pain and end-of-life pain. ?Special cautions and conditions are applied to clinician decision making in Emergency Department treatment of acute pain.??

Specifically in the context of Emergency Departments, the statement is made:

“… anticipated risks and benefits along with alternatives should be discussed with the patient. If deemed appropriate, only low-dose, short-acting opioids with a short duration of therapy should be prescribed.”

?Authors’ Observations:?In all clinical settings, the appropriate objectives for pain treatment are promotion of full healing and independent life, alleviation of suffering and promotion of patient quality of life – in each case, “to the extent possible.”?There should be no ethical distinction in principle between treatment of cancer versus non-cancer pain.?These objectives need to be explicitly acknowledged in the Preamble and appropriate subsections of the California Guidelines.

Both immediate-release and long-acting opioid analgesics have roles to play in all types of pain treatment.?Long-acting opioids may have the advantage of being more regularly scheduled, promoting better overnight rest.?They are also less prone to accidental overdose after the patient is discharged, once the patient’s sensitivity to medication is established during hospital admission and medication response monitoring.?

Mention is also appropriate in this section of training patients to use a medication dispenser and a daily schedule checklist to ensure regular dosing.?[op cit Ref 3]

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Older Adults and Pediatric Patients

Authors’ Observations:?As in previous sections, 90 MME thresholds should be removed.?Likewise, explicit recognition is in order for the low and historically stable rates of opioid overdose related mortality in older adults and pediatric patients, as compared with adults 25-60.?[Figure 1 and 2 above].?Also needed is acknowledgement that literally millions of Seniors are effectively managed on opioid doses exceeding 100 MME per day – and Centers for Medicare Services so-called “Over-Utilization” tools have a poor record of predicting hospital admissions for drug toxicity or overdose in this population. [Ref 11]

??[Ref 11]?Yu-Jung Jenny?Wei,?PhD; Cheng?Chen,?BSPharm; Amir?Sarayani,?PharmD; et al “Performance of the Centers for Medicare & Medicaid Services’ Opioid Overutilization Criteria for Classifying Opioid Use Disorder or Overdose?JAMA. 2019;321(6):609-611. doi:10.1001/jama.2018.20404 https://jamanetwork.com/journals/jama/article-abstract/2724180

Reasons for FDA safety labeling on codeine in cough medicines for children should be made explicit and discussed in detail.?The FDA safety alert was generated because of concerns for hyper-metabolism in generating high concentrations of prodrug components (morphine) ?that cross the blood-brain barrier.?

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Authors’ Concluding Remarks

Opioid analgesic medications have a 2,000-year history in the alleviation or management of pain. To imply that these medications are not safe and effective in such a purpose is simply ludicrous.?

Despite giving lip service to the need for individualized patient treatment under evidence-based guidelines, the proposed “California Guidelines for Prescribing Controlled Substances for Pain “ remains closely aligned to the 2016 and draft/proposed 2022 CDC Practice Guidelines?for ?prescription of opioids to adults with chronic non-cancer pain.?In the authors’ view, this is a fundamental and fatal error.?

It is now widely understood among clinicians that the CDC guidelines suffer from a pre-existing and deeply entrenched anti-opioid agenda, cherry picked and conflated research, disproportionate and unjustified emphasis on presumed but largely unproven “risks” versus benefits, an absence of validated instruments for assessing risk in individual patients, and potentially from financial and professional conflicts of interest among the CDC writers [Ref 12].

CDC guidelines have substantially injured and caused the desertion of millions of people in pain. The California guidelines as proposed in draft have the potential for continuing that damage for patients treated in that State.

As long as the proposed California Guidelines remain aligned with CDC, they will almost certainly continue to be used as an excuse for law enforcement to arbitrarily persecute doctors out of practice and sometimes to imprison them for doing no wrong other than treating pain patients with the most effective means possible. The Board may also find itself increasingly isolated from patient communities that simply do not believe its good will. ?It is therefore imperative that the California Medical Board divorce itself and the State from CDC misdirection.?

Fortunately, there are other frameworks from which Prescribing Guidelines can be written.?One such framework is outlined in great detail in [Ref 3] of these comments.?Another is of longer standing.?The World Health Organization Analgesic Ladder was first published in 1986 and has since been generalized beyond cancer pain [Ref 13].?This framework is taught in medical schools.?It has also been the subject of ongoing efforts to integrate recently emerging applications of so-called “interventional” pain therapies within its framework.?

Attachment 1, Appendix 1 to these comments offers a translation of the WHO Analgesic Ladder into 12 recommendations paralleling and correcting those of the CDC guidelines.?This material is not advocated as a final product or “standard”, but rather as a point of departure for CDC and California Medical Board reconsideration and refinement of the logic, goals and definitive medical evidence pertaining to treatment of pain.?

?Ref 12:?Chad Kollas, Terri Lewis, Beverly Schechtman and Carrie Judy, “Roger Chou’s Conflicts of Interest – the CDC’s 2016 Guideline for Prescribing Opoids for Chronic Pain Lost its Clinical and Professional Integrity”?Palimed – A Hospice and Palliative Medicine Blog, September 17, 2021. https://www.pallimed.org/2021/09/roger-chous-undisclosed-conflicts/

??Ref 13 Aabha A., Anekar;?Marco Cascella., “WHO Analgesic Ladder” , available full text at the US National Library of Medicine:?https://www.ncbi.nlm.nih.gov/books/NBK554435/

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Treatment of pain employing opioid analgesics is almost universally understood among practicing clinicians to involve the following measures:

Start with medications and minimum dose levels expected to be effective for the source and severity of pain. ?

Titrate up opioids (when employed) to desired effect, monitoring for and managing for undesired side effects (constipation, nausea, sleepiness, slowed reaction time, cognitive confusion or distortions).

Consider changing medication type or dose if pain remains refractory or side effects become unacceptable to the patient.

Monitor for development of medication tolerance.

Aggressively monitor for and treat depression or anxiety, with awareness of potential drug interactions.

Supplement analgesic treatment with adjudivant treatments or counseling support where available.

Actively engage family or community caregivers in a treatment and support team.

Taper medication down gradually as patient conditions improve or if the patient requests, again monitoring for and managing unacceptable effects.?Reversal of trial tapers is entirely appropriate if the patient experiences high levels of breakthrough pain.

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