This is a graphic representing the fictitious clinical facts that are starting to hit the fan

Is there any clinical justification to establish fixed opioid doses to treat chronic pain less than the FDA dosing guidelines

Based on the available information, there is generally no clinical justification to establish fixed opioid doses below FDA guidelines for treating chronic pain. The current clinical practice guidelines emphasize individualized patient care and avoiding inflexible dosing standards. Here are the key points:

1. Individualized approach: The CDC Clinical Practice Guideline for Prescribing Opioids for Pain (2022) emphasizes that recommendations should not be applied as inflexible standards of care across patient populations[1]. The guideline stresses the importance of individualized patient care and careful consideration of the benefits and risks of all treatment options.

2. Avoiding dosage thresholds: The CDC guideline specifically discourages the misapplication of opioid pain medication dosage thresholds as inflexible standards[1]. Instead, it emphasizes principles such as avoiding increasing dosage above levels likely to yield diminishing returns in benefits relative to risks to patients.

3. Regular evaluation: The Medical Board of California’s guidelines recommend regularly evaluating the benefit and harm of opioid therapy for chronic pain after starting treatment or following dose escalation[5]. This suggests that dosing should be adjusted based on individual patient response rather than adhering to fixed doses.

4. Patient-centered goals: The VA/DoD Clinical Practice Guidelines for Use of Opioids in the Management of Chronic Pain (2022) emphasize assessing patient-centered goals and improvements in function, rather than focusing solely on fixed dose limits[2].

5. Risk-benefit assessment: The FDA and other regulatory bodies consistently emphasize the need for careful risk-benefit assessment when prescribing opioids for chronic pain[4]. This approach is not compatible with establishing fixed doses below FDA guidelines without considering individual patient needs.

6. Transparency in decision-making: The FDA has been encouraged to be more transparent about its comprehensive, systems approach for incorporating public health considerations into regulatory decisions for opioid analgesics[6]. This suggests a move towards more nuanced and context-specific guidance rather than fixed dosing limits.

It’s important to note that while there is no general clinical justification for establishing fixed opioid doses below FDA guidelines, there may be individual cases where lower doses are appropriate based on patient-specific factors. Clinicians should consider factors such as the patient’s pain severity, functional improvement, risk factors for opioid-related harms, and individual response to treatment when determining appropriate dosing[1][5].

In conclusion, current clinical practice guidelines and regulatory approaches emphasize individualized patient care, regular assessment of benefits and risks, and avoiding inflexible dosing standards. Establishing fixed opioid doses below FDA guidelines for chronic pain treatment would not align with these evidence-based recommendations.

Citations:
[1] https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm
[2] https://www.healthquality.va.gov/guidelines/pain/cot/
[3] http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/AnestheticAndAnalgesicDrugProductsAdvisoryCommittee/UCM522688.pdf
[4] https://www.fda.gov/drugs/information-drug-class/timeline-selected-fda-activities-and-significant-events-addressing-substance-use-and-overdose
[5] https://www.mbc.ca.gov/Download/Publications/pain-guidelines.pdf
[6] https://www.fda.gov/media/165238/download
[7] https://www.fda.gov/media/86875/download
[8] https://health.ri.gov/healthcare/medicine/about/safeopioidprescribing/

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Here is a published MME calculator https://globalrph.com/medcalcs/morphine-equivalent-dose-med-opioid-conversions/   This is the infamous MME system that those “so-called experts” based their 2016 CDC opioid dosing guidelines and what many bureaucracies – like the DEA & VA – seemed to have codified those guidelines as a standard of care and best practices as well as maybe 30+ states have codified the same at the state level. 

This is a graphic representing the fictitious clinical facts that are starting to hit the fan

Does the Morphine Milligram Equivalent system have any clinical studies supporting its conclusions?

The Morphine Milligram Equivalent (MME) system has some clinical basis, but there are significant limitations and concerns about its scientific foundation and broad application:

1. Limited clinical evidence: The MME system is based on small clinical studies with limited populations[1][2]. These studies were originally intended to assist clinicians in determining initial doses when converting an individual patient’s opioid therapy, not as a broad risk assessment tool.

2. Lack of standardization: There is no single standard formula for calculating MMEs, leading to inconsistencies across different resources and calculators[2].

3. Oversimplification: The MME system does not adequately account for important patient and drug characteristics that can affect opioid potency and risk, such as opioid tolerance, pharmacogenetics, and differences between full and partial agonists[2].

4. Epidemiological support: While not directly validating MMEs, epidemiologic studies have shown an association between increasing daily opioid dose (measured in MMEs) and increasing risk of overdose[2]. However, these studies generally used broad MME threshold categories rather than precise conversions.

5. Concerns about misuse: Multiple experts have expressed concern that emphasizing specific MME thresholds as authoritative absolutes could lead to potentially harmful consequences, such as noncollaborative tapers[3].

6. Limited evidence for high doses: Few trials have evaluated opioid dosages of ≥90 MME/day, and there is some evidence of a plateauing effect at ≥50 mg MME/day in terms of pain relief[3].

7. Ongoing research needs: The FDA has recognized the need for further research to refine and improve the scientific basis of MME applications[1]. They held a workshop in 2021 to discuss knowledge gaps and research opportunities related to MMEs.

In summary, while the MME system has some clinical and epidemiological support, there are significant limitations in its evidence base and concerns about its broad application. More research is needed to address knowledge gaps and improve the scientific foundation of MME calculations and applications.

Citations:
[1] https://www.fda.gov/drugs/news-events-human-drugs/morphine-milligram-equivalents-current-applications-and-knowledge-gaps-research-opportunities-and
[2] https://www.fda.gov/media/150436/download
[3] https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm
[4] https://www.jprasurg.com/article/S1748-6815%2824%2900336-X/fulltext
[5] https://meps.ahrq.gov/data_files/publications/rf45/rf45.shtml

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Here is a published BME calculator  https://globalrph.com/medcalcs/benzodiazepine-converter-dosage-conversions/   Narxcare creates what they call an LME (Lorazepam Milligram Equivalent) value and includes it in their Narxcare PDM reports on pts that authorized healthcare professional can pull up reports on pts.

This is a graphic representing the fictitious clinical facts that are starting to hit the fan

does the Benzodiazepine equivalent calculations have any clinical studies that support its conclusions?

The benzodiazepine equivalent calculations do not have strong clinical studies supporting their conclusions. There are several important points to consider regarding the evidence base for benzodiazepine equivalency:

1. Limited evidence: Unlike opioid equivalence, benzodiazepine equivalence is poorly described in the literature and lacks a robust evidence base[1]. Most equivalence estimates are based on expert opinion, uncited tables in publications, and clinical practice rather than rigorous clinical studies[1].

2. Wide variability: Due to discrepancies in the literature, many benzodiazepine conversions may have potential conversion ranges that are extremely variable, sometimes by a factor of 10x or greater[1]. This highlights the lack of firm, evidence-based literature supporting specific conversion ratios.

3. Limitations of existing data: Much of the published equivalence data comes from alcohol withdrawal settings using oral dosage forms[1]. This limits the generalizability to other clinical scenarios or routes of administration.

4. Lack of standardization: Different sources may disagree on equivalency ratios, leading to the use of dose ranges rather than fixed conversions in many equivalency charts[3].

5. Clinical judgment emphasized: Given the limitations of the evidence, resources on benzodiazepine equivalency stress the importance of clinical judgment, patient monitoring, and gradual dose titration when making conversions[1][3].

6. Some specific conversions better studied: While most conversions lack strong evidence, there are exceptions. For example, the conversion between intravenous midazolam and lorazepam has been well-studied in mechanically ventilated patients[1].

7. Ongoing research: Some studies are evaluating the effectiveness of institutional benzodiazepine conversion protocols, but these are often limited to specific settings like pediatric intensive care units[5].

In conclusion, while benzodiazepine equivalency charts and calculators are widely used in clinical practice, they are not strongly supported by clinical studies. Healthcare providers should approach these conversions with caution, recognizing the limitations of the available evidence and the need for individualized patient care.

Citations:
[1] https://clincalc.com/Benzodiazepine/
[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7372528/
[3] https://emedicine.medscape.com/article/2172250-overview
[4] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4443548/
[5] https://www.researchgate.net/publication/326820719_Evaluation_of_IV_to_Enteral_Benzodiazepine_Conversion_Calculations_in_a_Pediatric_Intensive_Care_Setting

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How will the end of Chevron deference impact the DEA rules and regulations and enforcement of existing interpretations of the Control Substance Act that the DEA has made since its inception in 1973, which are now probably illegal?

The Supreme Court’s decision to overturn Chevron’s deference will likely have significant implications for the Drug Enforcement Administration’s (DEA) rules, regulations, and enforcement of existing interpretations of the Controlled Substances Act (CSA). Here are some key potential impacts:

1. Increased legal challenges: The elimination of Chevron deference opens the door for more frequent and potentially successful legal challenges to DEA regulations and interpretations of the CSA[1][4]. This could lead to a surge in litigation against the DEA’s existing rules and enforcement actions.

2. Judicial scrutiny of DEA interpretations: Courts will now be required to exercise their independent judgment when reviewing DEA interpretations of the CSA, rather than deferring to the agency’s expertise[1]. This means that judges will have more power to scrutinize and potentially overturn DEA regulations and enforcement actions.

3. Uncertainty for existing regulations: Many of the DEA’s longstanding interpretations and regulations based on the CSA may now be vulnerable to legal challenges[4]. This could create uncertainty for both the agency and regulated entities regarding which rules and enforcement practices will remain valid.

4. Potential scaling back of DEA authority: The ruling may lead to a scaling back or removal of numerous DEA rules and regulations that were previously upheld under Chevron deference[4]. This could potentially limit the DEA’s regulatory and enforcement powers in areas where the CSA is ambiguous.

5. Impact on scheduling decisions: The DEA’s authority to schedule and reschedule controlled substances may face increased scrutiny, as courts will now have more latitude to interpret the CSA’s criteria for drug scheduling independently.

6. Slower rulemaking process: The DEA may become more cautious in issuing new rules or interpreting the CSA, fearing potential legal challenges[3]. This could lead to a slower and more deliberate rulemaking process.

7. Congressional action: The ruling may prompt Congress to revisit and clarify aspects of the CSA to provide more explicit guidance, potentially reducing ambiguities that the DEA previously interpreted under Chevron deference[2].

8. Shift in enforcement strategies: The DEA may need to adjust its enforcement strategies to align with stricter judicial interpretations of the CSA, potentially affecting how it conducts investigations and prosecutions.

9. Retroactive challenges: There may be attempts to challenge past DEA actions and interpretations retroactively, although the extent to which courts will entertain such challenges remains to be seen.

10. Increased importance of statutory language: The precise wording of the CSA will become even more critical, as courts will focus more on traditional tools of statutory interpretation rather than deferring to DEA expertise[1].

It’s important to note that while many existing DEA interpretations and regulations may now be more vulnerable to legal challenges, they are not automatically invalidated by the Chevron ruling. Each regulation or interpretation would need to be challenged and evaluated individually by the courts. Additionally, while Chevron deference has been overturned, courts may still give some weight to agency expertise and experience in interpreting statutes, albeit to a lesser degree than before[1][2].

Citations:
[1] https://www.sidley.com/en/insights/newsupdates/2024/06/the-potential-implications-of-loper-bright-for-fda-and-fda-regulated-industries
[2] https://www.bhfs.com/insights/alerts-articles/2024/supreme-court-strikes-down-chevron-reshapes-administrative-law
[3] https://www.scientificamerican.com/article/supreme-courts-chevron-deference-decision-could-make-science-based/
[4] https://www.nytimes.com/2024/06/28/us/politics/chevron-deference-decision-meaning.html
[5] https://www.scotusblog.com/2024/06/supreme-court-strikes-down-chevron-curtailing-power-of-federal-agencies/

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CMS Incentivizes Payor Health Disparity Performance

https://www.specialtypharmacycontinuum.com/Policy/Article/06-24/CMS-Incentivizes-Payor-Health-Disparity-Performance/74138

Medicare Advantage and other health plans are starting to pay more attention to medication adherence, social determinants or drivers of health (SDOH), and where they can intervene in health disparities—not only because it’s the right thing to do but because it will soon affect their bottom line, speakers said at Asembia’s AXS24 Summit, in Las Vegas.

“There is now evidence that if you don’t address social drivers of health, you are not going to achieve good outcomes for a big percentage of the population,” said Christie Teigland, PhD, the vice president of research science and advanced analytics at Inovalon, a software and data solutions company.

SDOH drive about 80% of health outcomes, Dr. Teigland added. “Only about 20% of our health outcomes is due to the actual clinical care we get. The rest is related to things like income, education, the environment in which we live and our health behaviors. We need to understand them and how they might drive access to care and medication adherence.”

Medication adherence measures that are part of value-based payment systems are now being incorporated in the Centers for Medicare & Medicaid Services’ new Health Equity Index (HEI). The HEI was developed as an enhancement to Medicare Advantage plans, with a goal to incentivize contracts to perform well for beneficiaries with social risk factors, she said. For now, the population being studied includes members who are dually eligible for Medicare and Medicaid, those who receive a low-income subsidy, and those with disabilities, “not because those will be the only SDOH that are important, but because that’s what they have good access to data on,” Dr. Teigland said.

The HEI will consider Star Ratings of performance for 2024 and 2025 on 12 quality measures such as:

• adherence for cholesterol, hypertension and diabetes medications;
• statin use in people with diabetes; and
• rheumatoid arthritis management.

The goal of the HEI initiative is to look for disparities in outcomes among people with SDOH and where health plans can intervene, Dr. Teigland noted.

“Those big disparity gaps are really where plans are going to have to focus their efforts to do well on this Health Equity Index, because they’re going to get ranked against everyone else and get scored,” she said.

Performance on these measures will factor into a financial reward or bonus payment for plans starting in 2027. “The trick about these medication adherence measures [for diabetes, cholesterol and hypertension medications] is that they are triple-weighted in this index,” she explained. Plans that rank in the top will get 3 points, those that rank in the middle will receive no points and those in the bottom will get 3 points taken away from their score, “so these are going to be really impactful to plans.”

Although the HEI is initially starting with only a couple of social drivers, it behooves health plans to start tracking the effect of additional factors such as race/ethnicity, education level, household income, social isolation/living alone and English language proficiency, Dr. Teigland said. These entities also should be looking at their performance on medication adherence and other measures among members who are dually eligible, disabled or receive the low-income subsidy versus those who do not, using analytics and medical and pharmacy claims.

“It’s important that they do that exercise to understand where their biggest disparity gaps are,” she said. By doing so, “they can focus their limited resources to improve where it’s going to make the biggest difference in their HEI score.”

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Supreme Court guts agency power in seismic Chevron ruling

https://www.axios.com/2024/06/28/supreme-court-chevron-doctrine-ruling

The Supreme Court on Friday curtailed the executive branch’s ability to interpret laws it’s charged with implementing, giving the judiciary more say in what federal agencies can do.

Why it matters: The landmark 6-3 ruling along ideological lines overturns the court’s 40-year-old “Chevron deference” doctrine. It could make it harder for executive agencies to tackle a wide array of policy areas, including environmental and health regulations and labor and employment laws.

Driving the news: Chief Justice John Roberts, writing the opinion of the court, argued Chevron “defies the command of” the Administrative Procedure Act, which governs federal administrative agencies.

• He said it “requires a court to ignore, not follow, ‘the reading the court would have reached had it exercised its independent judgment as required by the APA.'”
• Further, he said it “is misguided” because “agencies have no special competence in resolving statutory ambiguities. Courts do.”

Roberts noted the court’s decision did not call into question prior cases that relied on Chevron, including holdings pertaining to the Clean Air Act, because they “are still subject to statutory stare decisis despite our change in interpretive methodology.”

• “Mere reliance on Chevron cannot constitute a ‘special justification’ for overruling such a holding,” he said.

Justice Elena Kagan, in a dissenting opinion, wrote that the ruling Friday was “yet another example of the Court’s resolve to roll back agency authority, despite congressional direction to the contrary.”

• “Congress knows that it does not — in fact cannot — write perfectly complete regulatory statutes,” she wrote. “It knows that those statutes will inevitably contain ambiguities that some other actor will have to resolve, and gaps that some other actor will have to fill. And it would usually prefer that actor to be the responsible agency, not a court.”
• She warned the decision “is likely to produce large-scale disruption.”
• “In one fell swoop, the majority today gives itself exclusive power over every open issue — no matter how expertise-driven or policy-laden — involving the meaning of regulatory law.”
• “The majority disdains restraint, and grasps for power.”

Context: The ruling marks another major victory for conservatives, who for decades have sought to limit the federal government’s ability to regulate businesses.

• In the wake of the court’s ruling, it’s expected that more federal rules will be challenged in the courts and judges will have greater discretion to invalidate agency actions.
• The decision comes one day after the Supreme Court curtailed federal agencies’ use of administrative law judges in another blow to the administrative state.

How it works: The doctrine was created by the Reagan-era Supreme Court in Chevron U.S.A. v. Natural Resources Defense Council in 1984 and has since become the most cited Supreme Court decision in administrative law.

• Under Chevron deference, courts would defer to how to expert federal agencies interpret the laws they are charged with implementing provided their reading is reasonable — even if it’s not the only way the law can be interpreted.
• It allowed Congress to rely on the expertise within the federal government when implementing everything from health and safety regulations to environmental and financial laws.

Zoom in: However, Chevron was challenged in two separate cases over a National Marine Fisheries Service regulation meant to prevent overfishing on commercial fishing vessels.

• Fishing companies challenging the regulation claimed the doctrine violated Article III of the Constitution by shifting the authority to interpret federal law from the courts to the executive branch.
• They also claimed it violated Article I by allowing agencies to formulate policy when only Congress should have lawmaking power.

The other side: The government argued that the doctrine had safeguards within it that prevented agencies from usurping Congress’s lawmaking authority.

• It noted that Chevron only applied to ambiguous text in laws passed by Congress and instances in which lawmakers had given interpretive authority to an agency.
• The doctrine was also necessary to limit federal judges’ abilities to make public policy when they may not have the expertise to do so and aren’t subject to democratic accountability, the government said.

Between the lines: Lawyers who worked pro bono to represent fishing companies involved in the cases are also staff attorneys for Americans for Prosperity, a libertarian political advocacy group funded by billionaire Charles Koch, the New York Times reported earlier this year.

• The political network associated with Charles Koch and his late brother, David Koch, have long championed efforts to get cases before the Supreme Court that, if decided in their favor, would roll back the federal government’s regulatory powers.
• The Koch network also successfully attracted Supreme Court Justice Clarence Thomas, who voted against the doctrine, to speak at at least one of its donor events in 2018, ProPublica reported last year.
• It’s unclear who purchased Thomas’ flight to the 2018 event, as he never reported it in his annual financial disclosure form. Thomas has attended at least two of such events in past years.

The big picture: In recent years, Chevron had fallen out of favor of the conservative-majority Supreme Court, which had declined to apply it or cite it in cases which it may once have applied.

• The ruling comes as some federal judges have taken a more active role in overruling agency expertise.
• For example, Texas District Judge Matthew Kacsmaryk last April paused the FDA’s original 23-year-old approval of the abortion pill mifepristone in a case that’s now to be decided by the Supreme Court.

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I made this blog post a couple of days ago and today got around to watching the video that I shared in the blog post. The 10 minute video is made by a non-profit that seems opposed to these guidelines.

UPDATED:Proposed tapering guideline by American Society of Addiction Medicine

some well-thought-out suggestions in commenting, like references supporting your position.

My first thought was..I’m going to waste all my time digging up references to what I consider common sense. Then again, I looked at who was involved with creating these proposed guidelines – a whole lot of academia types… who are focused on ADDICTION and they live and die on footnotes, citations, and references.

My whole life has been driven by the motto “work smarter not harder…”  I was tired and decided to take a nap, I turned on Pandora on my iPhone to listen to “My 60s Music Station”. My mind decided that “job one” was to find a shortcut to get answers and references!

I have been playing around with a couple of AI Chats for a few weeks. Asking them questions and what they come back with – normally within SECONDS – has often been IMPRESSIVE!

I put on my Pharmacist and my chronic pain advocate hats and started thinking about how chronic pain and anxiety intersect and how forced tapers and increased anxiety interact.

https://openai.com/chatgpt/

https://www.perplexity.ai/

So I asked the latter chat above: studies of chronic pain patients being forced tapered and anxiety levels increase and this is what I got back, including citations – SON OF A BITCH!

Based on the search results, there is evidence that tapering opioid medications in chronic pain patients can lead to increased anxiety levels and other negative outcomes:

1. Suggesting an opioid taper can trigger extreme anxiety in patients. Physicians are advised to acknowledge this anxiety, normalize it, and express empathy when broaching the subject of tapering[2].

2. A large study found that opioid dose tapering was significantly associated with increased risk of mental health crisis. Specifically, tapering was associated with an adjusted incidence rate of 7.4 mental health crisis events per 100 person-years compared to 4.3 events in non-tapered periods[3].

3. The risk of mental health crisis was even higher for patients tapering from higher baseline opioid doses. The study suggests that “especially careful mental health monitoring may be warranted for patients tapering from higher opioid doses”[3].

4. Standard opioid tapers tend to be associated with increased patient anxiety and higher pain ratings[4].

5. Anxiety and fear-based beliefs and behaviors have been strongly implicated in negative outcomes for chronic pain patients. Studies have shown that fear of movement and reinjury is a better predictor of self-reported disability than biomedical findings or pain intensity levels[1].

6. The fear of pain can create a self-perpetuating dynamic where patients avoid physical activity, leading to deconditioning and further disability. This same dynamic may apply to opioid use, as patients associate taking opioids with avoiding pain[1].

While these studies don’t specifically focus on “forced” tapering, they do highlight the significant anxiety and mental health risks associated with opioid tapering in chronic pain patients. The research suggests that tapering should be done carefully, with close monitoring of patients’ mental health, especially for those on higher doses. Physicians are advised to approach the topic sensitively and provide support throughout the tapering process to help manage patients’ anxiety and other potential negative outcomes.

Citations:
[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8427345/
[2] https://www.aafp.org/pubs/afp/issues/2020/0101/p49.html
[3] https://jamanetwork.com/journals/jama/fullarticle/2782643
[4] https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2022.820357/full
[5] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754260/

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https://downloads.asam.org/sitefinity-production-blobs/docs/default-source/guidelines/bzd-cpg-narrative-draft-for-public-comment.pdf?sfvrsn=6d96408_1

Above is the link that shows in the graphic – may have to click on the graphic a couple of times to get it to resize properly

Link to make comment

https://bit.ly/BZDCPG

I went back and did a few word searches.  I really didn’t feel like reading 146 pages.

The words I searched for – but did not find:

LME ( lorazepam milligram equivalent ) but there is an app for that https://globalrph.com/medcalcs/benzodiazepine-converter-dosage-conversions/

Pharmacogenomics

I am concerned that some well-intentioned bureaucrats will take these guidelines, and go down a similar path that was done with the 2016 CDC guidelines, and take these guidelines and codify them in many different ways.

I am also concerned that these guidelines seem to follow the Beers Criteria https://my.clevelandclinic.org/health/articles/24946-beers-criteria with the exception that they lowered the age to 60 y/o.

I did find this interesting on page 20:

Considerations for Tapering BZD5

The recommendations in this CPG should be interpreted in the context of shared decision-1
making with patients. In other words, when a recommendation says, “Clinicians should 2
consider”, it should be understood to include “in partnership with the patient”
In 2020, the FDA updated the required Boxed Warning for BZD medications to describe the 6
risks of physical dependence, withdrawal, and SUD.33 The associated Drug Safety7
Communication encouraged prescribers to carefully weigh the risks and benefits of BZD8
medications, limit the dose and duration to what is needed to achieve the clinical goal, and 9
monitor patients for BZD misuse and use disorder. When prescribing BZDs, it is important for10
prescribers to have a thoughtful strategy for medication management that regularly reassesses the11
risks and benefits of continued prescribing, as well as a patient-centered plan for tapering the12
medication when the benefits no longer outweigh the risks.13
The risks of BZD use continue while a patient continues to take the medication. In addition, the14
risk for physical dependence and BZD use disorder, particularly in patients who use alcohol or15
other drugs, increases with time.34 As such, long-term BZD use is frequently associated with16
more risks than benefits. Significant risks include oversedation, cognitive impairment, falls,17
motor vehicle crashes, and nonfatal and fatal overdose. 9 Despite this, clinicians often encounter18
patients who have been taking prescribed BZD for months or years.19
While short-term BZD use is associated with decreased anxiety and insomnia, it is commonly20
recommended that use not exceed 4 weeks, because at that point clinical benefits often decrease21
while risks increase.28,35 Meta-analyses of patients taking BZD for insomnia demonstrated minor22
improvements in sleep onset, increased duration, and decreased nighttime awakenings.36,37
23
However, therapeutic effects diminish in days or weeks due to changes in BZD receptor density24
and/or affinity resulting from chronic use, while risks continue. A meta-analysis of RCTs25
comparing BZD to placebo for insomnia in adults over age 60 showed 3.8 -fold increase in26
daytime sedation, and 4.8-fold increase in cognitive impairment and increased incidence of27
psychomotor effects (e.g., falls, motor vehicle accidents). 36 Another meta-analysis showed28
increased risk for fractures associated with current and recent BZD use in older adults.

https://youtu.be/nDZggME3uUo?si=SJASo-arlnn_ZL2b

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Popular weight loss and diabetes drugs linked to increased risk of rare form of blindness

https://www.cnn.com/2024/07/03/health/ozempic-wegovy-blindness-rare-risk/index.html

People who take Ozempic or Wegovy may have a higher risk of developing a rare form of blindness, a new study suggests. Still, doctors say it shouldn’t deter patients from using the medicines to treat diabetes or obesity.

Last summer, doctors at Mass Eye and Ear noticed an unusually high number of patients with non-arteritic anterior ischemic optic neuropathy, or NAION, a type of eye stroke that causes sudden, painless vision loss in one eye.

The condition is relatively rare — up to 10 out of 100,000 people in the general population may experience it — but the doctors noted three cases in one week, and each of those patients was taking semaglutide medications.

A look back at six years of medical records showed that people with diabetes were more than four times more likely to be diagnosed NAION if they were taking a prescription semaglutide, and those who were overweight or obese were more than seven times more likely to experience the condition if they were taking the medication. The risk was found to be greatest within the first year of receiving a prescription for semaglutide.

The study, published Wednesday in the medical journal JAMA Ophthalmology, cannot prove that semaglutide medications cause NAION. And the small number of patients — an average of about 100 cases were identified each year — from one specialized medical center may not apply to a broader population.

Novo Nordisk, the manufacturer of the only semaglutide medications in the US, emphasized that the data in the new study is not sufficient to establish a causal association between the use of semaglutide medications and NAION.

“Patient safety is a top priority for Novo Nordisk, and we take all reports about adverse events from the use of our medicines very seriously,” a company spokesperson wrote in an email to CNN.

Semaglutide prescriptions have soared in the US, which could raise the number of people at risk for a potential side effect. And NAION is the second-leading cause of optic nerve blindness after glaucoma.

But even with an increased risk, the condition remains relatively uncommon.

“The use of these drugs has exploded throughout industrialized countries and they have provided very significant benefits in many ways, but future discussions between a patient and their physician should include NAION as a potential risk,” lead researcher Dr. Joseph Rizzo, director of the neuro-ophthalmology at Mass Eye and Ear and a professor at Harvard Medical School, said in a news release. “Our findings should be viewed as being significant but tentative, as future studies are needed to examine these questions in a much larger and more diverse population.”

Experts agree that the potential risk of NAION should not deter the use of semaglutide medications to treat diabetes or obesity.

“In the ever-changing landscape of systemic therapies, being vigilant for potential new disease associations is a duty we all share on behalf of patients,” Susan Mollan, an ophthalmologist with the University Hospitals Birmingham in the UK wrote in a related commentary. But the large number of people who are taking semaglutide should raise confidence that the absolute risk of developing NAION as a result is rare.

The ways that semaglutides interact with the eyes are not entirely understood. And the exact cause of NAION is not known either. The condition causes damage to the optic nerve, but there is often no warning before vision loss.

Changes in blood sugar levels can affect the shape of an eye’s lens and may affect vision, said Dr. Disha Narang, an endocrinologist and director of obesity medicine at Endeavor Health in Chicago. She was not involved in the new study.

And the use of semaglutides, which prompt the body to create more insulin to reduce blood sugar, has been previously linked to temporary vision changes — new or worsening cases of diabetic retinopathy, or damage to blood vessels at the back of the eye — likely related to the rapid improvement of blood sugars.

The US Food and Drug Administration-approved labels for both Ozempic and Wegovy include vision changes among potential side effects, and Novo Nordisk is exploring the link between semaglutide use and diabetic retinopathy in a trial which they expect to complete 2027.

“Patient safety is paramount at the FDA and we continuously review available sources of data and new information on potential risks of drugs, including GLP-1 receptor agonists, and update labeling as needed to communicate new information on potential risks to healthcare providers and to patients as soon as possible,” Chanapa Tantibanchachai, a press officer with the FDA, told CNN over email.

While there is a “biologically plausible mechanism” for a potential interaction, “‘association is not causation’ and diabetes mellitus is a known risk factor for NAION,” Dr. Andrew Lee, clinical spokesperson for the American Academy of Ophthalmology and neuro-ophthalmologist at Houston Methodist Hospital, told CNN in an email. He was not involved in the new study.

For now, patients who are taking semaglutide or considering treatment should discuss the risks and benefits with their doctors, especially those who have other known optic nerve problems such as glaucoma or preexisting visual loss, experts say

“It is important to consult with ophthalmology if patients experience visual changes,” Narang said. “It is important to make sure patients are consulting with physicians who are also comfortable prescribing semaglutide and talking through what may be clinically relevant versus irrelevant, and discussing benefits versus risks of long-term therapy.”

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Pain Doesn’t Belong on a Scale of Zero to 10

https://www.medpagetoday.com/opinion/second-opinions/110926

The real answer is long, complicated, and not measurable in this one-dimensional way

Over the past 2 years, a simple but baffling request has preceded most of my encounters with medical professionals: “Rate your pain on a scale of zero to 10.”

I trained as a physician and have asked patients the very same question thousands of times, so I think hard about how to quantify the sum of the sore hips, the prickly thighs, and the numbing, itchy pain near my left shoulder blade. I pause and then, mostly arbitrarily, choose a number. “Three or four?” I venture, knowing the real answer is long, complicated, and not measurable in this one-dimensional way.

Pain is a squirrely thing. It’s sometimes burning, sometimes drilling, sometimes a deep-in-the-muscles clenching ache. Mine can depend on my mood or how much attention I afford it and can recede nearly entirely if I’m engrossed in a film or a task. Pain can also be disabling enough to cancel vacations, or so overwhelming that it leads people to opioid addiction. Even 10+ pain can be bearable when it’s endured for good reason, like giving birth to a child. But what’s the purpose of the pains I have now, the lingering effects of a head injury?

The concept of reducing these shades of pain to a single number dates to the 1970s. But the zero-to-10 scale is ubiquitous today because of what was called a “pain revolution” in the ’90s, when intense new attention to addressing pain — primarily with opioids — was framed as progress. Doctors today have a fuller understanding of treating pain, as well as the terrible consequences of prescribing opioids so readily. What they are learning only now is how to better measure pain and treat its many forms.

About 30 years ago, physicians who championed the use of opioids gave robust new life to what had been a niche specialty: pain management. They started pushing the idea that pain should be measured at every appointment as a “fifth vital sign.” The American Pain Society went as far as copyrighting the phrase. But unlike the other vital signs — blood pressure, temperature, heart rate, and breathing rate — pain had no objective scale. How to measure the unmeasurable? The society encouraged doctors and nurses to use the zero-to-10 rating system. Around that time, the FDA approved oxycodone hydrochloride (OxyContin), a slow-release opioid painkiller made by Purdue Pharma. The drugmaker itself encouraged doctors to routinely record and treat pain, and aggressively marketed opioids as an obvious solution.

To be fair, in an era when pain was too often ignored or undertreated, the zero-to-10 rating system could be regarded as an advance. Morphine pumps were not available for those cancer patients I saw in the ’80s, even those in agonizing pain from cancer in their bones; doctors regarded pain as an inevitable part of disease. In the emergency room where I practiced in the early ’90s, prescribing even a few opioid pills was a hassle: It required asking the head nurse to unlock a special prescription pad and making a copy for the state agency that tracked prescribing patterns. Regulators (rightly) worried that handing out narcotics would lead to addiction. As a result, some patients in need of relief likely went without.

After pain doctors and opioid manufacturers campaigned for broader use of opioids — claiming that newer forms were not addictive, or much less so than previous incarnations — prescribing the drugs became far easier and were promoted for all kinds of pain, whether from knee arthritis or back problems. As a young doctor joining the “pain revolution,” I probably asked patients thousands of times to rate their pain on a scale of zero to 10 and wrote many scripts each week for pain medication, as monitoring “the fifth vital sign” quickly became routine in the medical system. In time, a zero-to-10 pain measurement became a necessary box to fill in electronic medical records. The Joint Commission on the Accreditation of Healthcare Organizations made regularly assessing pain a prerequisite for medical centers receiving federal healthcare dollars. Medical groups added treatment of pain  to their list of patient rights, and satisfaction with pain treatment became a component of post-visit patient surveys. (A poor showing could mean lower reimbursement from some insurers.)

But this approach to pain management had clear drawbacks. Studies accumulated showing that measuring patients’ pain didn’t result in better pain control. Doctors showed little interest in or didn’t know how to respond to the recorded answer. And patients’ satisfaction with their doctors’ discussion of pain didn’t necessarily mean they got adequate treatment. At the same time, the drugs were fueling the growing opioid epidemic. Research showed that an estimated 3% to 19% of people who received a prescription for pain medication from a doctor developed an addiction.

Doctors who wanted to treat pain had few other options, though. “We had a good sense that these drugs weren’t the only way to manage pain,” Linda Porter, PhD, director of the National Institutes of Health’s Office of Pain Policy and Planning, told me. “But we didn’t have a good understanding of the complexity or alternatives.” The enthusiasm for narcotics left many varietals of pain underexplored and undertreated for years. Only in 2018, a year when nearly 50,000 Americans died of an overdose, did Congress start funding a program — the Early Phase Pain Investigation Clinical Network, or EPPIC-Net — designed to explore types of pain and find better solutions. The network connects specialists at 12 academic specialized clinical centers and is meant to jump-start new research in the field and find bespoke solutions for different kinds of pain.

A zero-to-10 scale may make sense in certain situations, such as when a nurse uses it to adjust a medication dose for a patient hospitalized after surgery or an accident. And researchers and pain specialists have tried to create better rating tools — dozens, in fact, none of which was adequate to capture pain’s complexity, a European panel of experts concluded. The Veterans Health Administration, for instance, created one that had supplemental questions and visual prompts: A rating of 5 correlated with a frown and a pain level that “interrupts some activities.” The survey took much longer to administer and produced results that were no better than the zero-to-10 system. By the 2010s, many medical organizations, including the American Medical Association and the American Academy of Family Physicians, were rejecting not just the zero-to-10 scale but the entire notion that pain could be meaningfully self-reported numerically by a patient.

In the years that opioids had dominated pain remedies, a few drugs — such as gabapentin and pregabalin for neuropathy, and lidocaine patches and creams for musculoskeletal aches — had become available. “There was a growing awareness of the incredible complexity of pain — that you would have to find the right drugs for the right patients,” Rebecca Hommer, MD, EPPIC-Net’s interim director, told me. Researchers are now looking for biomarkers associated with different kinds of pain so that drug studies can use more objective measures to assess the medications’ effect. A better understanding of the neural pathways and neurotransmitters that create different types of pain could also help researchers design drugs to interrupt and tame them.

Any treatments that come out of this research are unlikely to be blockbusters like opioids; by design, they will be useful to fewer people. That also makes them less appealing prospects to drug companies. So EPPIC-Net is helping small drug companies, academics, and even individual doctors design and conduct early-stage trials to test the safety and efficacy of promising pain-taming molecules. That information will be handed over to drug manufacturers for late-stage trials, all with the aim of getting new drugs approved by the FDA more quickly.

The first EPPIC-Net trials are just getting underway. Finding better treatments will be no easy task, because the nervous system is a largely unexplored universe of molecules, cells, and electronic connections that interact in countless ways. The 2021 Nobel Prize in Physiology or Medicine went to scientists who discovered the mechanisms that allow us to feel the most basic sensations: cold and hot. In comparison, pain is a hydra. A simple number might feel definitive. But it’s not helping anyone make the pain go away.

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