Feds Warn About Rapid Opioid Tapers

By Pat Anson, PNN Editor

Federal health officials are once again urging doctors not to rapidly decrease or abruptly stop prescribing opioid medication to chronic pain patients.

In an editorial published in the Journal of the American Medical Association (JAMA), three federal health officials warn that sudden opioid tapering significantly increases the risk of harm to patients, resulting in increased hospitalizations and emergency room visits.

“There are concerning reports of patients having opioid therapy discontinued abruptly and of clinicians being unwilling to accept new patients who are receiving opioids for chronic pain, which may leave patients at risk for abrupt discontinuation and withdrawal symptoms,” the editorial warns.

The editorial was written by Deborah Dowell, MD, of the Centers for Disease Control and Prevention, Wilson Compton, MD, of the National Institute on Drug Abuse, and Brett Girior, MD, of the U.S. Public Health Service. Dowell is one of the co-authors of the CDC’s controversial opioid guideline, which has been widely used as an excuse by doctors, insurers and pharmacies to impose mandatory limits on prescribing.  

Even before its release in March 2016, pain patients and advocates warned the CDC guideline would result in rapid tapering, patient abandonment and suicide.

But not until April of this year – after three years of needless deaths and suffering -- did the FDA and CDC start urging doctors to be more cautious in their tapering.

It then took another six months for the Department of Health and Human Services (HHS) to produce a 6-page guide for doctors on how to taper patients.

bigstock-Man-s-hand-with-empty-pill-bot-104277830(1).jpg

“The HHS guide and current guidelines emphasize that tapering should be individualized and should ideally proceed slowly enough to minimize opioid withdrawal symptoms and signs. Physical dependence occurs as early as a few days after consistent opioid use, and when opioids have been prescribed continuously for longer than a few days, sudden discontinuation may precipitate significant opioid withdrawal,” the JAMA editorial warns.

The HHS tapering guide urges doctors not to dismiss pain patients and to share decision making with them when developing a taper program.

“If the current opioid regimen does not put the patient at imminent risk, tapering does not need to occur immediately. Take time to obtain patient buy-in,” the guideline cautions. “There are serious risks to non-collaborative tapering in physically dependent patients, including acute withdrawal, pain exacerbation, anxiety, depression, suicidal ideation, self-harm, ruptured trust, and patients seeking opioids from high-risk sources.”

The guide suggests tapers of 5% to 20% every four weeks, although slow tapers of 10% a month may be appropriate for patients taking opioids for more than a year.

A recent study of tapering in Vermont found only 5 percent of patients had a tapering period longer than 90 days. The vast majority (86%) were rapidly tapered in 21 days or less, including about half who were cut off from opioids without any tapering. Many of those patients were hospitalized for an “opioid-related adverse event” -- a medical code that can mean anything from severe withdrawal symptoms to acute respiratory failure.

Another recent study at a Seattle pain clinic found that tapered patients had an unusually high death rate, with some dying from suspected overdoses.

Meanwhile, not a single word of the CDC opioid guideline has changed since federal health officials finally acknowledged it was harming patients and needed clarification.

CDC: Still Not Enough Naloxone   

By Pat Anson, PNN Editor

The Trump Administration is stepping up efforts to increase prescribing of naloxone, an overdose recovery drug credited with saving thousands of lives.

Although naloxone prescriptions have increased dramatically, a new CDC Vital Signs report estimates that nearly 9 million additional prescriptions could have been dispensed last year if every patient with a high-dose opioid prescription was offered naloxone.  Patients are considered “high risk” if they take an opioid dose of 50 morphine milligram equivalent (MME) or more per day.

Naloxone has been used for years by first responders and emergency medical providers to revive overdose victims. Current efforts are focused on expanding access to the drug by prescribing it directly to patients considered at risk of an overdose.

In 2018, CDC researchers say only one naloxone prescription was dispensed for every 70 high-dose opioid prescriptions nationwide. Naloxone “under-prescribing” was even more acute in rural counties, which are nearly three times more likely to be ranked low in naloxone dispensing than metropolitan counties.

Naloxone2.jpg

“It is clear from the data that there is still much needed education around the important role naloxone plays in reducing overdose deaths. The time is now to ensure all individuals who are prescribed high-dose opioids also receive naloxone as a potential life-saving intervention,” CDC Director Robert Redfield, MD, said in a statement.

Ironically, federal policies contribute to the under-prescribing. In 2018, most (71%) Medicare prescriptions for naloxone required a copay, compared to 42% for commercial insurance.

In January, the Food and Drug Administration encouraged drug makers to make naloxone available over-the-counter without a prescription. The FDA even developed an OTC label for Narcan, a naloxone nasal spray that sells for about $135. Seven months later, the FDA could not confirm to PNN that any company had submitted an application for an OTC version of naloxone.

Last year the Department of Health and Human Services released guidance urging doctors to “strongly consider” prescribing naloxone to patients on any dose of opioids when they also have respiratory conditions or obstructive sleep apnea, are co-prescribed benzodiazepines, have a mental health or substance abuse disorder, or a history of illegal drug use or prescription opioid misuse.

Many states are also taking steps to increase naloxone prescribing. California now requires doctors to “offer” naloxone prescriptions to pain patients deemed at high risk of an overdose. State law does not make the prescriptions mandatory, yet some patients say they were “blackmailed” by pharmacists who refused to fill their opioid scripts unless naloxone was also purchased. Patients around the country report similar experiences.   

Unintended Consequences

The drumbeat for naloxone comes at a time when sales are already booming. There were 556,000 naloxone prescriptions in 2018, twice as many as in 2017.

There’s no doubt naloxone saves lives, but some researchers say the drug has had little effect on the overdose crisis and may in fact be making it worse. In a recent study published by SSRN, two economics professors warned of “unintended consequences” if naloxone becomes more widely available.

“We expect these unintended consequences to occur through two channels. First, the reduced risk of death makes opioid abuse more appealing, leading some to increase their opioid use — or use more potent forms of the drug — when they have naloxone as a safety net. Some of those abusers may become criminally active to fund their increased drug use,” wrote Jennifer Doleac, PhD, Texas A&M University, and co-author Anita Mukherjee, PhD, University of Wisconsin.

“Furthermore, expanding naloxone access might not in fact reduce mortality. Though the risk of death per opioid use falls, an increase in the number or potency of uses means the expected effect on mortality is ambiguous.”

The researchers said there were anecdotal reports of “naloxone parties” where attendees used heroin and prescription opioids to get high knowing they could be revived. News reports have also quoted first responders who are frustrated that the same opioid abusers “are saved again and again by naloxone without getting treatment.”

Lessons from ‘The United States of Opioids’

By Roger Chriss, PNN Columnist

Harry Nelson’s new book “The United States of Opioids: A Prescription for Liberating a Nation in Pain” looks closely and productively at the opioid overdose crisis. It comments on origins and causal factors, and offers pragmatic policy ideas for addressing it. The book is succinct and well-organized, designed for easy reading and reference.

Nelson starts with a dire description of addiction and overdose, calling the U.S. opioid crisis “American healthcare’s self-inflicted wound.” He then gives a brief history of opioids, explaining the three waves of the crisis, culminating in illicit fentanyl and “an increasing crackdown on physician overprescribing.”

Nelson touches on the history and science of opioids, then looks at causes of the crisis. These include not only Purdue Pharma and the Sacklers, but also drug distributors, retailers and health insurers. Institutional and regulatory failures on opioids are not ignored.

“The overarching problem when it comes to physician overprescribing has been insufficient training and education on how to prescribe opioids,” he writes. “The FDA approved these drugs and oversaw the data concerning the risks of their misuse, abuse, addiction, and overdose.”

But Nelson digs deeper, looking at the underlying social and cultural determinants that play into the longer term. He cites a 2018 University of Pittsburgh study that underscores that opioids are part of a broader trend in which abuse of multiple drugs and a rising drug overdose rate “that shows no signs of slowing, with sub-epidemics of different drugs over time.”

Unlike other books, Nelson writes in depth about how to address the crisis: “I believe that our attention should first be focused on a host of intersecting trends that point to suffering in America — parallel crises that include suicidality, anxiety, depression, and pain.”

He explores other options for pain management, from NSAIDs and nerve blocks to non-pharmacological techniques: “It is critical to push insurers and government programs to cover non-opioid treatment, even if it means spending more to achieve this priority.”

Nelson includes a whole chapter on cannabis and other alternative therapies for opioid addiction, in particular kratom and psychedelics. He is optimistic but tentative about cannabis: “Despite the potential to address health issues, consumers need to be cautious about both the claims and contents of cannabis products.”

He also looks at addiction treatment, including AA-type abstinence programs and medication-assisted therapy, and notes that “the biggest challenge in addiction treatment is the complexity of addiction itself.”

Nelson is highly critical of much of the response to the crisis to date: “When I think about the government and health system’s approach for taking on the opioid crisis, the thing that strikes me most is how much it feels tactical rather than strategic.”

Nelson condemns the rampant fraud and patient brokering in the recovery industry. But he also points out that addiction treatment itself needs improvement.

“We will know that addiction treatment has ‘arrived’ in terms of its integration into healthcare when we have relatively uniform professional and program licensure requirements from state to state — something seemingly decades away,” he wrote.

Nelson lists seven general recommendations for the crisis in his OPIOIDS acronym:

  • Outreach for prevention and early intervention

  • Physician improvements

  • Innovation in pain and addiction care

  • Overdose interventions

  • Interdiction off illicit opioids

  • Data analytics to better track the crisis

  • Strengthening access to addiction care

He emphasizes the value of harm reduction, improving social capital, and organizing prevention in schools and the workplace — instead of “stop gap” measures that do little beyond preventing fatal overdoses.

“The key to solving the opioid crisis lies in not being satisfied with tackling the overdose death issue, but in addressing two of the fundamental problems that got us here: the inadequate management of ongoing issues for people living with chronic pain, which overlaps with the second problem of people living with an opioid use disorder (OUD),” he writes.

Finally, Nelson gives a warning: “If we think about the opioid crisis as the ‘canary in the coal mine,’ it’s warning us that we need to address a much bigger, toxic set of problems.”

For all the book offers, it also has problems. Nelson overstates the number of people with opioid use disorder, misrepresents the complex nature of opioid initiation, and misconstrues the varied trajectory of heroin addiction. Most importantly, Nelson gives little attention to rising rates of cocaine and methamphetamine overdose deaths, and ignores that most overdoses involve multiple drugs.

“The United States of Opioids” offers a suite of tools and ideas for moving forward, a refreshing change from the many righteous rants or poignant laments about the crisis.

Roger Chriss.jpg

Roger Chriss lives with Ehlers Danlos syndrome and is a proud member of the Ehlers-Danlos Society. Roger is a technical consultant in Washington state, where he specializes in mathematics and research.

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represents the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.

Gabapentinoids Raise Risk of Suicide and Overdose in Younger People

By Pat Anson, PNN Editor

Gabapentinoids – a class of nerve medication widely prescribed to treat chronic pain – increase the risk of suicide, overdose, traffic accidents and head or body injuries in younger people, according to a large new study published in The British Medical Journal.

Sales of the two main gabapentinoids, pregabalin (Lyrica) and gabapentin (Neurontin), have tripled in recent years in the United States, where they are often promoted in prescribing guidelines as safer alternatives to opioids.

A team of researchers followed nearly 192,000 people enrolled in the Swedish Prescribed Drug Register who filled prescriptions for gabapentinoids on at least two consecutive occasions from 2006 to 2013. That information was compared to data in the Swedish Patient Register, which collects information on hospital admissions and outpatient care, as well as the Swedish Cause of Death Register.

Over the study period, researchers found that patients taking gabapentinoids had higher rates of suicide or suicidal behavior (5.2%), unintentional overdose (8.9%), traffic accidents (6.3%) and head or body injuries (36.7%) than the general population.

The risks were strongest for people who were prescribed pregabalin and were most pronounced among adolescents and young adults aged 15 to 24.  Patients aged 55 and older taking gabapentinoids were not at greater risk.

Researchers believe the drugs may have more impact on younger people because they have faster metabolisms, which could lead to withdrawal problems that affect their impulsivity and emotions.

bigstock-Painkiller-Pill--73847413.jpg

“Overall, gabapentinoids seem to be safe for a range of outcomes in older people. However, the increased risks found in adolescents and young adults prescribed gabapentinoids, particularly for suicidal behaviour and unintentional overdoses, warrant further research,” said lead author Seena Fazel, MD, of the University of Oxford in England.

“If our findings are triangulated with other forms of evidence, clinical guidelines may need review regarding prescriptions for young people, and those with substance use disorders. Further restrictions for off-label prescription may need consideration.”

Pregabalin is approved by the FDA to treat diabetic nerve pain, fibromyalgia, post-herpetic neuralgia caused by shingles and spinal cord injuries; while gabapentin is approved for epilepsy and post-herpetic neuralgia. Both drugs are also widely prescribed off-label to treat back pain, depression, migraine and other chronic conditions.

Gabapentinoids are increasingly being used recreationally by addicts who have found the medications enhance the effects of heroin and other opioids. The drugs were recently classified as controlled substances in the UK.

Gabapentin is not currently scheduled as a controlled substance by the DEA, while Lyrica is classified as a Schedule V controlled substance, meaning it has low potential for addiction and abuse.  

A recent clinical review found little evidence the drugs should be used off-label to treat pain and that prescribing guidelines often exaggerate their effectiveness. The CDC’s controversial opioid guideline, for example, calls gabapentin and pregabalin “first-line drugs” for neuropathic pain.

“Despite documentation that these drugs were promoted improperly for off-label treatment of pain, the recent rapid increase in prescribing of gabapentinoids suggests a persisting sense among clinicians that gabapentinoids are highly effective pain medications,” wrote Christopher Goodman, MD, and Allan Brett, MD, of the University of South Carolina School of Medicine.

“Guidelines and review articles have contributed to this perception by often uncritical extrapolation from FDA-approved indications to off-label use.”

Prescription Opioids Play Minor Role in Massachusetts Overdoses

By Pat Anson, PNN Editor

Two new studies in Massachusetts – one of the states hardest hit by the overdose crisis – highlight the role of multiple substances in most overdose deaths and how limiting the supply of prescription opioids has failed to reduce the number of drug deaths.

Researchers at Boston Medical Center's Grayken Center for Addiction analyzed toxicology reports on nearly 2,250 fatal overdoses involving opioids in Massachusetts between 2014 and 2015. Overdose data in Massachusetts is considered more reliable because it is one of the few states to extensively use toxicology testing.

Only 9 percent of the deaths in Massachusetts involved prescription opioids alone. Most of the overdoses (72%) involved illicit fentanyl or heroin, while one in five (19%) involved a combination of heroin, fentanyl or prescription opioids.

Other substances such as alcohol, marijuana, stimulants (cocaine and methamphetamine) and non-opioid medications (benzodiazepines and gabapentin) were also frequently involved.

“Using multiple substances, in addition to opioids, is the rule rather than the exception for opioid-related deaths,” researchers reported in the journal Drug and Alcohol Dependence.

“Our study draws attention to the heterogeneity of the problem at hand and that there is not a one-size-fits-all approach to addressing the overdose epidemic, which is increasingly driven by polysubstance use.”

bigstock-American-Drugs-4379874.jpg

Over half of the Massachusetts overdoses involved someone with a diagnosed mental illness. Homelessness and a recent incarceration also raised the risk of a fatal overdose involving both opioids and stimulants.

"As a provider, these findings indicate a pressing need to address and treat not just opioid use disorder, but other substances that patients are misusing," said lead author Joshua Barocas, MD, an infectious disease physician at BMC. "To truly make a difference in reducing opioid overdose deaths, we must tackle issues such as homelessness and access to mental health services. This means not only investing in treatment but also implementing tailored programs that address the specific barriers to accessing care."

Opioid Prescriptions Down 39% since 2015

The number of opioid prescriptions has declined significantly in Massachusetts over the last four years, according to a recent report from the state’s Department of Public Health. In the first quarter of 2019 there were over 518,000 prescriptions filled for Schedule II opioids such as hydrocodone and oxycodone – a 39% decline from the first quarter of 2015.

But the decrease in prescriptions has failed to make much of a dent in Massachusetts’ opioid overdose rate, which peaked in 2016 with 2,100 deaths and remains stubbornly high.  

SOURCE: MASSACHUSETTS DEPARTMENT OF PUBLIC HEALTH

SOURCE: MASSACHUSETTS DEPARTMENT OF PUBLIC HEALTH

In 2018, nearly nine out of ten opioid-related deaths (89%) in the state involved illicit fentanyl, with cocaine (39%), heroin (32%), and benzodiazepines (40%) such as Xanax also commonly found.

Only about ten percent of the overdose deaths in the fourth quarter of 2018 involved prescriptions opioids, virtually unchanged from the 2014-2015 study.

Heroin and Fentanyl Fueling Veteran Overdoses, Not Rx Opioids

By Pat Anson, PNN Editor

The U.S. Department of Veterans Affairs has taken a number of steps in recent years to reduce opioid prescribing for military veterans and their families. In 2015, the VA adopted the CDC opioid guideline before it was even finalized. Two years later, the agency adopted a clinical practice guideline for VA doctors that strongly recommends against prescribing opioids to patients for more than 90 days.

Both measures were intended to address “mounting concerns about prescription drug abuse and an overdose epidemic among veterans.”

But a new study has found that the “epidemic” of opioid overdoses among veterans is not fueled by prescriptions opioids – but by heroin, illicit fentanyl and other synthetic opioids obtained on the black market.

Researchers at the University of Michigan and VA Ann Arbor Healthcare System reported in the American Journal of Preventive Medicine that overdose deaths from all opioids increased by 65 percent for veterans from 2010 to 2016. But when then looked closer at prescription data on nearly 6,500 veterans who died, they found an unexpected trend.

"The percentage of veterans who had received an opioid pain prescription in the year before their opioid overdose death dropped substantially over this time period," says lead author Allison Lin, MD, an addiction psychiatrist at the VA Ann Arbor.

In 2010, half of the veterans who died of any opioid overdose had filled an opioid prescription in the three months before they died, and two-thirds had filled a prescription in the last year.

But by 2016, only a quarter of those who overdosed had filled an opioid prescription in the last three months, and 41 percent had done so in the past year.

At the same time, the death rate from heroin or from taking multiple opioids nearly quintupled, and the death rate from synthetic opioids such as fentanyl rose more than five-fold.

veterans opioids.jpg

“Interventions on opioid overdose prevention have often focused on those receiving opioid prescriptions; if we're only screening for risk in that population, this shows we will miss a lot," said Lin. "We really have to think about opioid overdose prevention and substance use disorder treatment more broadly, to determine where the greatest unmet need is, increase treatment access and accessibility, and improve outcomes."

The VA provides health services to 6 million veterans and their families. Over half the veterans being treated at VA facilities suffer from chronic pain, as well as other conditions that contribute to it, such as depression and post-traumatic stress disorder.

A 2016 study of veterans found a strong link between heroin use and the non-medical use of prescription opioids. Having a long-term prescription for opioids to treat chronic pain was not found to be a significant risk factor for heroin use.

Record Decline in Opioid Prescriptions

By Pat Anson, PNN Editor

Often lost in the debate over opioid medication is that prescriptions for the drugs have been falling for years — a trend that appears to be accelerating. The volume of prescription opioids dispensed in the U.S. last year fell 17 percent, the largest annual decline ever recorded, according to a new study by the health analytics firm IQVIA. Opioid prescriptions have dropped 43% since their peak in 2011.

“Decreases in prescription opioid volume have been driven by changes in clinical use, regulatory and reimbursement policies and legislation, all of which have increasingly restricted prescription opioid use since 2012,” the report found.

The biggest drop was in high dose opioid prescriptions of 90 MME (morphine milligram equivalent) or more, which account for 43% of the decline. Low dose prescriptions of 20 MME or less have remained relatively stable, falling just 4 percent.

While opioid prescriptions have fallen significantly, addiction and overdose rates continue to soar, fueled in large part by illicit fentanyl, heroin and other black market opioids.

“We saw many more people receiving medication-assisted treatment (MAT) for opioid addiction. Our research shows new therapy starts for MATs increased to 1.2 million people in 2018, nearly a 300 percent increase compared with those seeking addiction help in 2014,” said Murray Aitken, IQVIA senior vice president.

“This is an important indicator of the effects of increased funding and support for treatment programs to address addiction.”

A recent report by the Bipartisan Policy Center estimates the federal government spent nearly $11 billion since 2017 subsidizing the addiction treatment industry, much of it spent on MAT drugs such as buprenorphine (Suboxone).

Drug maker Indivior recently reported the buprenorphine market had double digit growth in the first quarter of 2019, and that “growth continues to be driven primarily by Government channels.”

bigstock-Prescription-Medication-1608757.jpg

Hydrocodone Prescriptions Drop

For the 7th consecutive year, prescriptions fell for hydrocodone-acetaminophen combinations such as Vicodin, Lortab and Norco. Once the #1 most widely dispensed drug in the nation, hydrocodone now ranks fifth, behind drugs used to treat thyroid deficiency, high blood pressure and high cholesterol.

Only 68 million prescriptions for hydrocodone were dispensed last year, half the number that were filled in 2011.

U.S. HYDROCODONE PRESCRIPTIONS (MILLIONS)

Source: IQVIA

Due to fears about addiction and overdose, hydrocodone was reclassified by the DEA as a Schedule II controlled substance in 2014, requiring new prescriptions for every refill.

“My hydrocodone has been cut in half and my pain is out of control. I feel like a criminal, like I am committing a crime each time I pick up my prescription. I now have to visit my doctor once a month to receive my script,” one patient told us.

“I was prescribed hydrocodone over the last couple of decades for severe chronic pain with very positive effects. Now I am unable to carry out a lifestyle for a man my age, I'm basically done/finished.  My way of life is over,” a disabled veteran wrote.

“Stop denying the patients that have real pain. I don’t use it to get high. Hydrocodone is the only thing that has helped my back pain. I’ve tried a lot of things but nothing helps. It frees me of enough of the pain that I can function like a normal person,” another patient said.

The shift away from hydrocodone and other opioids has benefited pharmaceutical companies that make non-opioid medications such as Neurontin (gabapentin) and Lyrica (pregabalin).  Prescriptions for gabapentin reached 67 million last year – nearly the same as hydrocodone.

These trends have yet to show much benefit for pain patients, who increasingly report their pain is poorly treated. In a recent PNN survey of nearly 6,000 patients, over 85% said their pain and quality of life are worse since the release of the CDC opioid prescribing guideline. One in five say they are hoarding opioid medication because they fear losing access to it in the future.