Did OxyContin's Reformulation Really Lead to More Heroin Use?

By Roger Chriss, PNN Columnist

A common belief in the opioid overdose crisis is that the reformulation of OxyContin in 2010 led to a large-scale shift to heroin. Seven years after making the pills hard-to-crush to discourage snorting or injecting, The Washington Post reported the abuse-deterrent reformulation had made OxyContin “the chief driver of the explosion in heroin overdose deaths.”

The primary source of this claim is a National Bureau of Economic Research (NBER) paper that states “a substantial share of the dramatic increase in heroin deaths since 2010 can be attributed to the reformulation of OxyContin.”

The NBER paper used data from the National Survey on Drug Use and Health (NSDUH) and the Drug Enforcement Administration to assess usage levels of OxyContin and other prescription opioids, and data from the National Vital Statistics System to measure overdose deaths.

The researchers found that “states with the highest initial rates of OxyContin misuse experienced the largest increases in heroin deaths.”

But this conclusion is now being challenged. A recent study in the journal Addiction Behavior looked at NSDUH data from 2005 through 2014 to evaluate the impact of the reformulation on individuals with a history of OxyContin misuse.

The results showed “no statistically significant effects of the reformulation” on prescription opioid misuse or heroin use. In fact, researchers found a “net reduction in the odds” of heroin initiation after the reformulation.

“Thus, the reformulation of OxyContin appears to have reduced prescription pain reliever misuse without contributing to relatively greater new heroin use among those who misused OxyContin prior to the reformulation,” the authors concluded.

Psych Congress also reported there was little evidence of a shift to heroin from prescription opioids, saying drug trafficking data “don't fully support the often-heard conclusion that efforts to limit access to prescription opioids led to a mass migration to heroin."

Murky Data

The reason for the different conclusions is not clear. But much of what is assumed about abuse-deterrent reformulation is not holding up. Last summer, STAT News reported that rates of OxyContin abuse were similar or higher three years after the drug was reformulated. According to one survey, less than 5 percent of long-term abusers gave up OxyContin, suggesting the reformulation didn’t accomplish much.

Data on heroin use also includes considerable uncertainty, and applying state-level data-sets to understand individual usage patterns is tricky. Plus, data on overdose fatalities can be hard to parse since many victims die with multiple drugs in their systems, and toxicology reporting varies by state.

Since OxyContin’s reformulation, six other opioid medications have been approved by the FDA with abuse deterrent properties, costing drug makers hundreds of millions of dollars in research and development expenses.

Figuring out what happens after a prescription opioid is reformulated is important. Current public health policy and prescribing practices are assuming risks and benefits based on limited evidence. If something different or perhaps more complex is happening, then we need to look harder and make changes.

The implications here are also important, including determining liability and damages in the opioid lawsuits, developing effective public health measures for addiction treatment and the overdose crisis, and creating better risk assessment for pain management.

The impacts of the OxyContin reformation may be smaller and more subtle than previously thought. If the new findings hold, then we may have to rethink the benefits of abuse-deterrent formulations and the trajectory of heroin use. In other words, we need to keep looking closely at the overdose crisis and not assume we have it fully figured out.

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

Is It Too Early to Declare Victory in the Opioid Crisis?

By Pat Anson, PNN Editor

Wisconsin’s two U.S. Attorneys are taking a victory lap on the one-year anniversary of threatening letters they sent to 180 doctors, physician assistants and nurse practitioners in the state. The letters warned the providers that if they continue to prescribe “relatively high levels” of opioid medication — above doses recommended by the CDC — they could face civil or criminal prosecution.

In a joint news release this week, Scott Blader and Matthew Krueger, U.S. Attorneys for the Western and Eastern Districts of Wisconsin, said there has been “a substantial decrease in opioid prescribing” among providers who received the warning letters.

“Thanks partly to this initiative and the consistent efforts by the Wisconsin medical community to stem over-prescribing, Wisconsin has seen substantial progress in the fight against opioid abuse,” the news release claimed. “Total opioid prescriptions in Wisconsin have declined by 30 percent between 2016 and 2019, according to data from the Wisconsin Prescription Drug Monitoring Program. The letters sent by the United States Attorneys appear to have amplified this downward trend.” 

The release did not indicate if any provider who received the warning letter had been charged with a crime or if any of their patients has been harmed by their prescribing. The two U.S. Attorneys’ offices did not respond to a request for further information.

President Trump also claimed progress was being made in the overdose crisis during his State of the Union address on Tuesday.

“We are curbing the opioid epidemic, Drug overdose deaths declined for the first time in nearly 30 years. Among the states hardest hit, Ohio is down 22 percent, Pennsylvania is down 18 percent, Wisconsin is down 10 percent — and we will not quit until we have beaten the opioid epidemic once and for all,” Trump said.

Fentanyl Deaths Increasing

A closer look at the overdose numbers shows that it’s way too early to declare victory. A CDC report last week found that drug deaths declined over 4% in 2018, led by a significant drop in overdoses involving hydrocodone, oxycodone and other painkillers. But deaths linked to illicit fentanyl and other street drugs are surging – threatening to reverse the overall trend.

“One thing that we’re seeing is that the decline doesn’t appear to be continuing in 2019. It appears rather flat, maybe actually increasing a little bit,” said Robert Anderson, PhD, Chief of the Mortality Statistics Branch, National Center for Health Statistics. “We do know that deaths due to synthetic opioids like fentanyl are continuing to increase into 2019 and we’re seeing increases similarly with cocaine and psychostimulants with abuse potential, the methamphetamine deaths."

The most recent overdose stats from Wisconsin are also revealing, as the following two charts will show. While deaths in the state involving prescription opioids began declining in October 2017 -- over a year before the U.S. Attorneys even sent their warning letters – overdoses linked to fentanyl and other synthetic opioids are rising.

SOURCE: WISCONSIN DEPARTMENT OF HEALTH SERVICES

Nearly twice as many Wisconsinites are dying from heroin and fentanyl overdoses than from prescription opioids – a fact that is omitted in the news release from the U.S. Attorneys.

The only mention of fentanyl was the kind available by prescription. Prosecutors took credit for a Wausau physician being sentenced to three months in prison for writing “fraudulent fentanyl prescriptions” to six patients.  

A better representation of what’s happening in Wisconsin – and around the nation – is last month’s arrests of over three dozen people accused of trafficking illicit fentanyl, heroin and cocaine in Milwaukee. The drugs were allegedly shipped from Puerto Rico and Mexico, meaning drug cartels thousands of miles away recognize that there’s a demand for street drugs in Wisconsin’s largest city.

In 2019, 370 people died of drug overdoses in Milwaukee County. It was iIlicit fentanyl — not prescription opioids — that was the leading cause of death.

That doesn’t deserve a victory lap.

DEA: Fentanyl 'Primary Driver' of Overdose Crisis

By Pat Anson, PNN Editor

The U.S. Drug Enforcement Administration has released the 2019 National Drug Threat Assessment, a comprehensive report that outlines the threats posed to the nation by drug traffickers and the abuse of illicit drugs.

Not surprisingly, the annual report found that illicit fentanyl is the “primary driver” behind the overdose crisis, with fentanyl and its analogs involved in more overdose deaths than any other illicit drug. Fentanyl is a synthethic opioid 50 to 100 times more potent than morphine. The drug is prescribed legally to treat severe pain, but illicit versions of fentanyl have flooded the black market.

Of growing concern to the DEA is the appearance of illegal pill press operations in the U.S. that are manufacturing millions of counterfeit painkillers and other medications, using fentanyl powder smuggled in from China and Mexico.

“Fentanyl will remain a serious threat to the United States as record numbers of individuals suffer fatal overdoses from illicit fentanyl sourced to foreign clandestine production,” the report warns.

“Clandestine fentanyl pill pressing operations will likely increase as DTOs (drug trafficking organizations) seek to appeal to the large pill abuser population in the United States, with counterfeit fentanyl-containing pills continuing to be associated with clusters of overdoses and deaths due to inconsistent mixing and often unexpectedly high potency.”

With China cracking down on illicit fentanyl laboratories, the DEA expects the primary source of fentanyl production to shift to Mexico and India.  

Fewest Prescription Opioids Since 2006

One bright spot in the DEA report is the continuing decline in overdoses involving prescription opioids. As PNN reported, overdose deaths involving natural and semisynthetic opioids, which include painkillers such as oxycodone and hydrocodone, were 3.8% lower in 2018 than in 2017.   

The DEA said the supply of prescription opioids is now at its lowest level since 2006. DEA production quotas for hydrocodone and oxycodone have been cut nearly in half since 2016, with further cuts proposed for 2020.

But while the retail supply of opioid medication has fallen dramatically, the diversion of opioids and other controlled drugs by medical professionals and wholesale distributors – so-called “lost in transit” diversion – has soared. There were 18,604 lost in transit reports filed in 2018, nearly six times the number reported in 2010.

“It is unclear if these dosage units are being diverted, destroyed, or truly lost. Although representative of only a small number of DEA registrants, diversion by physicians, nurses, and other medical professionals and their staff remains a threat to communities across the United States,” the report warns.

The DEA predicts “a steady decrease” in the supply of opioids over the next several years and that prescription drug abusers “may shift to abusing heroin, illicitly produced synthetic opioids, and methamphetamine to obtain similar effects, which may further increase overdose deaths through at least 2020.”

The DEA said the threat posed by psychostimulants such as methamphetamine and cocaine is “worsening and becoming more widespread.” While most cocaine users prefer to snort or inject the drugs, law enforcement agencies are starting to find cocaine in tablet or pill form.

“Whether these instances are harbingers of a new trend, an experiment, or simply the result of accidental contamination within poly-drug operations remains to be seen. Tableting and capsulizing cocaine may allow traffickers to capitalize on the considerably larger CPD user market with a different version of cocaine, further maximizing profits,” the DEA said.

Finally, while the DEA officially considers the herbal supplement kratom a “drug of concern” and once tried to ban it, there is once again no mention of kratom in its annual drug threat assessment.

Drug Overdose Deaths Fell 4% in 2018

By Pat Anson, PNN Editor

Drug overdose deaths in the United States dropped in 2018 for the first time in nearly three decades, according to a new CDC report that highlights the rapidly changing nature of the overdose crisis. While deaths linked to many prescription opioids declined, overdoses involving illicit fentanyl, cocaine and psychostimulants rose.

There were 67,367 drug overdose deaths in the U.S. in 2018, a 4.1% decline from 2017 when there were 70,237 fatal overdoses.

The rate of overdose deaths involving natural and semisynthetic opioids, which includes painkillers such as oxycodone and hydrocodone, was 3.8% lower. There were nearly 2,000 fewer deaths linked to painkillers in 2018 than there was the year before.

However, the decline in deaths involving opioid medication was more than offset by a continuing spike in overdoses linked to synthetic opioids other than methadone, which primarily involves illicit fentanyl and fentanyl analogs. The death rate in that category rose 9% from 2017 to 2018.

SOURCE: CDC

While the overall trend is encouraging, a top CDC official was cautious about preliminary data for drug deaths in 2019.

“One thing that we’re seeing is that the decline doesn’t appear to be continuing in 2019. It appears rather flat, maybe actually increasing a little bit,” said Robert Anderson, PhD, Chief of the Mortality Statistics Branch, National Center for Health Statistics.

“We do know that deaths due to synthetic opioids like fentanyl are continuing to increase into 2019 and we’re seeing increases similarly with cocaine and psychostimulants with abuse potential, the methamphetamine deaths."

Overdose deaths often involve multiple drugs, so a single death might be included in more than one category and be counted multiple times. A death that involved both fentanyl and cocaine, for example, would be classified by CDC researchers as an overdose involving both synthetic opioids and cocaine.

“There’s a lot of overlap between these categories and so a death may be actually counted in multiple categories, in two or more in many instances, making it difficult to partition the decline,” said Anderson. “We really don’t have a good handle on how best to do that.”  

Opioid Prescriptions Decline Significantly

A second CDC study on opioid prescribing shows that prescriptions have declined significantly in 11 states with prescription drug monitoring programs (PDMPs) that participate in the Prescription Behavior Surveillance System (PBSS). The 11 states include California, Ohio, Texas and Florida, and represent over a third of the U.S. population.

The decline in opioid prescriptions in the states ranged from 14.9% to 33% from 2010 to 2016, indicating that prescriptions were falling long before the CDC released its controversial opioid guideline in March, 2016. Significant declines were also noted in high dose opioid prescriptions, the average daily dose and in prescriptions obtained from multiple providers.

Despite the nearly decade-long decline in prescriptions, CDC researchers continue to blame opioid medication for the ongoing overdose crisis, offering little evidence to support that view.

“PDMP data collected by PBSS indicate that steady progress is being made in reducing the use and possible misuse of prescription-controlled substances in the United States. However, some persons who were misusing prescription opioids might have transitioned to heroin or illicitly manufactured fentanyl, a change that has made the drug overdose epidemic and associated overdose rates more complex,” researchers said.

“Because the opioid overdose epidemic began with increased deaths and treatment admissions related to opioid analgesics in the late 1990s, initiatives to address overprescribing might eventually result in fewer persons misusing either prescription or illicit drugs. Reduction in overprescribing opioids might lead ultimately to a decrease in overall overdose deaths.”

PDMP data for the CDC study came from the PBSS monitoring program at Brandeis University, where Dr. Andrew Kolodny is Co-Director of the Opioid Policy Research Collaborative. Kolodny is the founder and Executive Director of Physicians for Responsible Opioid Prescribing (PROP), an activist group that has long been critical of opioid prescribing.

Alcohol Deaths Double in U.S.

By Pat Anson, PNN Editor

Alcohol related deaths in the U.S. have doubled in the past two decades, according to a new study that highlights an under-reported aspect of the overdose crisis: while deaths involving prescription opioids are declining, alcohol abuse appears to be increasing.

Researchers at the National Institute on Alcohol Abuse and Alcoholism (NIAAA) found the number of death certificates mentioning alcohol more than doubled from 35,914 in 1999 to 72,558 in 2017.

By comparison, 17,029 deaths in 2017 involved a prescription opioid, according to CDC estimates.

“The current findings suggest that alcohol-related deaths involving injuries, overdoses and chronic diseases are increasing across a wide swath of the population. The report is a wakeup call to the growing threat alcohol poses to public health,” said NIAAA Director Dr. George Koob.

Nearly 1 million alcohol-related deaths were recorded between 1999-2017. About half the deaths resulted from chronic liver disease or overdoses on alcohol alone or with other drugs.

Researchers noted that alcohol-related deaths were increasing among people in almost every age, race and ethnic group. Their study is published in Alcoholism: Clinical & Experimental Research.

“Taken together, the findings of this study and others suggests that alcohol-related harms are increasing at multiple levels – from ED visits and hospitalizations to deaths. We know that the contribution of alcohol often fails to make it onto death certificates. Better surveillance of alcohol involvement in mortality is essential in order to better understand and address the impact of alcohol on public health,” said Koob.

Other drugs besides alcohol are increasingly involved in overdoses. A recent analysis of over one million urine drug tests conducted by Millennium Health found that positive results for illicit fentanyl rose by 333% since 2013, while positive rates for methamphetamine increased by 486 percent.

That study, published in JAMA Network Open, found that positive rates for heroin and cocaine peaked in 2016 and appear to be declining.

The analysis is similar to a 2019 report from the National Institute on Drug Abuse, which found that drug deaths involving prescription opioids and heroin have plateaued, while overdoses involving methamphetamine, cocaine and benzodiazepines have risen sharply.

Unreliable Data

Just how reliable is the federal data on drug use and overdoses? Not very, according to another study published in Drug and Alcohol Dependence.

Troy Quast, PhD, an associate professor at the University of Florida’s College of Public Health, compared overdose data from the Florida Medical Examiners Commission (FMEC) to drug deaths in a CDC database. Quast found the federal data significantly undercounted overdose deaths in Florida linked to cocaine, benzodiazepines, amphetamines and other drugs.

Florida medical examiners are required by law to wait for complete toxicology results before submitting an official cause of death to FMEC. It often takes weeks or months to identify the exact drug or drugs that cause an overdose. By contrast, the CDC data is based on death certificates filed by coroners and other local authorities, which often don't include detailed toxicology reports. This causes significant differences between the two databases.

Between 2003 and 2017, roughly one-in-three overdose deaths in Florida involving illicit or prescription opioids were not reported by the federal government. The discrepancy wasn’t limited to opioids. Quast also found that nearly 3,000 deaths in Florida caused by cocaine were not included in the CDC database. Overdose deaths involving benzodiazepines and amphetamines were also significantly under-reported.

"The CDC data are widely reported in the news and referenced by politicians, which is problematic since those estimates significantly undercount the true scope of the epidemic for specific drugs," said Quast. "The rate of under-reporting for all overdose deaths in Florida is near the national average, so the problem is not to the state."

This isn’t the first time the reliability of CDC data has been questioned. In 2018, CDC researchers admitted that many overdoses involving illicit fentanyl and other synthetic black market opioids were erroneously counted as prescription drug deaths. As result, federal estimates prior to 2017 "significantly inflate estimates" of prescription opioid deaths.

Even the adjusted estimates are imprecise, because the number of deaths involving diverted prescriptions or counterfeit drugs is unknown and drugs are not identified on 20% of death certificates. When the drugs are listed, many overdoses are counted multiple times by the government because more than one substance is involved.

The federal government is working to improve the collection of overdose data. Over 30 states are now enrolled in the CDC's Enhanced State Opioid Overdose Surveillance program, which seeks to improve overdose data by including toxicology reports and hospital billing records.

In 2017, the program reported that nearly 59 percent of overdose deaths involved illicit opioids like fentanyl and heroin, while 18.5% had both illicit and prescription opioids. Less than 18% tested positive for prescription opioids only.

A recent study of drug deaths in Massachusetts found that only 1.3% of overdose victims who died from an opioid painkiller had an active prescription for the drug – meaning the medication was probably diverted, stolen or bought on the street.  

Rx Drug Databases Linked to Heroin Deaths

By Pat Anson, PNN Editor

Prescription drug monitoring programs (PDMPs) in the U.S. are often promoted as critical tools in preventing opioid abuse and addiction. But a new study suggests that some PDMPs may be having the unintended effect of driving pain patients to street drugs such as heroin.

PDMPs in 49 states (the one exception is Missouri) allow physicians and pharmacists to consult a drug database to see if patients are “doctor shopping” or getting too many opioid prescriptions. The databases are also used by law enforcement agencies to identify doctors who prescribe high levels of opioid medication.  

A team of researchers reported in the International Journal of Drug Policy that there was a “consistent, positive, and significant association” between the adoption of PDMPs and fatal heroin overdoses. By the third year of a state adopting a PDMP, there was a 22% overall increase in heroin fatalities.

The increase was not uniform across all PDMPs.  States with “Proactive” PDMPs, which are more likely to flag suspicious activity by doctors and patients and report them to law enforcement, had a slight decline in heroin overdoses, while states with weaker PDMPs had significant increases in heroin deaths.

“The study just shows that heroin is an alternative to prescription pain medicine,” says John Lilly, DO, a Missouri physician who opposes PDMPs. “The harder it is to get prescription pain medicine, the more heroin deaths and presumably heroin use occurs. Market forces at work. Heroin is not the big alternative. It’s illicit fentanyl.”

It's not the first time researchers have found mixed results on the effectiveness of PDMPs. A 2018 study also found an increase in heroin deaths associated with PDMPs, along with a decline in overdoses linked to prescription opioids.

"It's pretty striking that this is the second study where we have found that PDMPs with robust features such as sending unsolicited alerts about outlying prescribing and dispensing patterns to PDMP users, and providing more open access to PDMP data, are associated with a small decline in opioid overdose deaths," said senior author Magdalena Cerdá, DrPH, an associate professor and director of the Center for Opioid Epidemiology and Policy at NYU Langone Health.

"In our prior study we found that these types of PDMPs were associated with a decline in prescription opioid overdose deaths, and this new study suggests Proactive PDMPs may also have a downstream protective effect on heroin overdose risk."

Cerdá and her colleagues believe PDMPs that aggressively flag and report suspicious activity will help stop inappropriate prescribing sooner and better identify patients in need of addiction treatment, preventing their transition to heroin. 

“To the best of our knowledge, this study is the first to identify specific classes of PDMP characteristics that are most strongly associated with changes in rates of fatal heroin poisonings,” said lead author Silvia Martins, MD, an associate professor of epidemiology at Columbia Mailman School of Public Health. “We believe those authorized to access the data should be trained to protect individual privacy and confidentiality and ensure that it is used only to improve care for the patient.”

DEA Sues Colorado for Access to PDMP

Patient privacy is at issue in an unusual lawsuit filed last week by the Drug Enforcement Administration against Colorado’s Board of Pharmacy. The DEA subpoenaed the board to release patient data from Colorado’s PDMP to assist in the investigation of two pharmacies. But the state refused to comply, citing privacy concerns.

“The Department of Regulatory Agencies is committed to combating the opioid epidemic that remains a devastating issue for many Colorado communities,” spokeswoman Jillian Sarmo said in an email to the Colorado Sun. “We continue to work with our partners in other agencies in this fight, but we have an obligation to do so in a targeted and thoughtful manner that ensures the privacy of the hundreds of thousands of individual patients in the state whose personal prescription records have no connection to any criminal activity and whose disclosure has no relevance to any criminal investigation.”

Also named in the DEA lawsuit is Appriss, Inc., a private company that Colorado and dozens of other states use to collect and maintain their PDMP data. If a federal judge rules in favor of the DEA in Colorado, it could set a legal precedent that would force Appriss to release prescription data from other states.

“We are taking this action as part of our office’s efforts to aggressively pursue law enforcement investigations of anyone who may be breaking the law,” U.S. Attorney Jason Dunn said in a statement.  “We are disappointed with the refusal to comply with these lawful subpoenas, a refusal that has forced us to seek aid from the court in getting the information we need to carry out important law enforcement investigations aimed at combating the prescription drug abuse epidemic.” 

A recent study undermines much of the association between overdoses and prescription opioids that are obtained legally. Researchers say only 1.3% of overdose victims in Massachusetts had an active prescription for the opioid that killed them — meaning PDMPs would have little value in preventing the other 98.7% of deaths.

High Number of Youths Using Rx Opioids

By Pat Anson, PNN Editor

A large new analysis of drug use by teenagers and young adults in the U.S. has found a surprisingly high level of prescription opioid use. In a survey of over 56,000 youths, researchers found that 21% of teens and 32% of young adults said they had used opioid medication in the past year.

"The percentages were higher than we expected," said first author Joel Hudgins, MD, of Boston Children's Hospital's Division of Emergency Medicine. "They really highlight how common use of prescription opioids is in this vulnerable population."

The data from the 2015-2016 National Survey on Drug Use and Health doesn’t necessarily reflect the environment that exists today. Opioid prescriptions have fallen by 43% since their peak and last year alone declined by a record 17 percent. Many pain patients — of all ages — now have trouble getting opioids prescribed and filled.

During the study period, nearly 4% of teens and 8% of young adults reported misusing prescription opioids or having an opioid use disorder.

Misuse was defined as using opioids “in any way that a doctor did not direct you to use them,” while a use disorder was classified as recurrent use that causes significant impairment and failure to meet major responsibilities at home, work or school.

Researchers were surprised by some of the findings, which are published in the online journal PLOS One. Among youths who reported misusing prescription opioids, 57% said they obtained them from friends or relatives and only 25% percent came from healthcare providers.

"In previous studies in adults, opioids were more commonly obtained from a physician," Hudgins says. "Our findings show that the focus of prevention and treatment should include close friends and family members of adolescents and young adults, not simply prescribers."

Youths who misused opioids, particularly the young adults, often reported using other substances, including cocaine (36%), hallucinogens (49%), heroin (9%) and inhalants (30%). At least half had used tobacco, alcohol, or cannabis in the past month.

In a previous study, the same researchers found relatively high rates of opioid prescribing to youths visiting emergency rooms and outpatient clinics. About fifteen percent of youths were given opioids during ER visits from 2005 to 2015.

"Given these rates of opioid use and misuse, strong consideration should be given to screening adolescents and young adults for opioid use when they receive care," says Hudgins.

More recent surveys have found a steady decline in the misuse of prescription opioids by young people. The most recent Monitoring the Future Survey found that only 3.4% of high school seniors misused opioid medication in 2018.

Misuse of Vicodin and OxyContin among 12th graders has fallen dramatically over the past 15 years, from 10.5% in 2003 to 1.7% in 2018 for Vicodin, and from 4.5% in 2003 to 2.3% in 2018 for OxyContin.   

Why America's Opioid Crisis Is Really a Drug Crisis

By Pat Anson, PNN Editor

A new report from the CDC challenges much of the conventional thinking about the opioid crisis, particularly the role played by prescription opioids. Other medications can be even more risky.

For example, twice as many Americans overdosed on the anti-anxiety drug alprazolam (Xanax) in 2017 than those who died after taking hydrocodone (Vicodin).

Gabapentin (Neurontin), a pain reliever thought to be safer than opioids, was linked to more fatal overdoses than tramadol (Ultram).

And here’s a shocker: the antihistamine diphenhydramine (Benadryl) is the 10th deadliest drug in the United States.

CDC researchers say illicit fentanyl, heroin and cocaine were involved in far more overdoses than any opioid medication. And methadone, an addiction treatment drug that’s supposed to prevent overdoses, was linked to more drug deaths than hydrocodone.

Only three opioid pain medications — oxycodone, morphine and hydrocodone — made the top 10 list of drugs involved in 2017 overdoses.

TOP 10 DRUGS INVOLVED IN 2017 OVERDOSES

SOURCE: CDC

CDC researchers used a text analysis to scan electronic death certificates to find which drugs were most commonly involved in overdoses. The methodology is imperfect, since it includes drugs that were not necessarily the cause of death, but it provides a more thorough picture of which drugs are driving America’s overdose crisis.

The analysis also uncovered distinct regional differences. Deaths from heroin in 2017 were highest in New England, New York, and the mid-Atlantic states, while methamphetamine was the deadliest drug in most of the West, Southwest and Mountain states.

The 2017 analysis is likely already dated, as counterfeit medications made with illicit fentanyl have caused hundreds of overdose deaths this year on the west coast, from San Diego to Seattle.     

Doctors Targeted for Opioid Prescribing

While legal prescription opioids are not involved in most drug overdoses, they continue to be the focus of the Department of Justice and other law enforcement agencies, which mine prescription drug databases looking for signs of suspicious prescribing.

We reported this week on the case of a California pain doctor who paid a $125,000 fine to settle DOJ allegations that he “illegally prescribed opioids.”

“It was extortion and there’s nothing I was able to do about it. It’s sad and pathetic,” said Dr. Roger Kassendorf.

Federal prosecutors built their case against Kassendorf by analyzing prescription data to identify five of his patients who were on relatively high doses of opioids. None of the five were harmed or overdosed while under the care of Kassendorf, who admits his medical records could have been better. He settled to avoid a more expensive court fight.

It’s a familiar story to other doctors who’ve been targeted by regulators or law enforcement.

“If you study every board case and every indictment, they claim inadequate medical records. It’s their fall back in every case, so in case they lose on the facts, they can save face by being the documentation police,” said Dr. Mark Ibsen, a Montana primary care physician. “As with overprescribing, they never define what under-documentation is.”

Ibsen was initially accused by the Montana medical board of overprescribing opioids, but his medical license was suspended for inadequate medical records. Ibsen had to go to court to get the suspension overturned.

“The prescription drug registry is an excellent document in support of the physician. Given that it is a database available to all physicians in each state, it is hard to claim inadequate documentation for any physician,” Ibsen said.

“There are many doctors and nurse practitioners targeted by law enforcement solely because of the amount of opioids they prescribe. This is inappropriate. No one can assess the quality of care by just looking at the amount of drugs a provider prescribes,” says Dr. Lynn Webster, a pain management specialist and PNN columnist. 

“Providers are often forced to accept plea agreements to avoid incarceration, because they don't have the resources to fight the system. They will often do this to protect their families. There are bad doctors who should be put away, but most are trying to do the best they can within a system that is biased against people in pain and opioids.”

The pressure on physicians is so intense that many have lowered doses or stopped prescribing opioids altogether. That’s forcing pain patients to seek treatment with other doctors — who then run the risk of being flagged as a “high prescriber” if they accept new patients who need opioids.

Health Canada Supports Use of Prescription Heroin to Treat Addiction

By Pat Anson, PNN Editor

Canada’s national health agency -- Health Canada – is supporting efforts to expand the use of pharmaceutical-grade heroin in treating opioid addiction.

A treatment center in Vancouver, BC is currently the only clinic in North America that provides diacetylmorphine -- prescription heroin – to opioid addicts. Other clinics may soon follow, after last month’s publication of the first clinical guideline for using injectable diacetylmorphine and hydromorphone to treat people with severe opioid use disorder.

Heroin is classified as a Schedule I controlled substance in the United States, making it illegal to prescribe for any purpose. But pharmaceutical grade heroin is legal in Canada, UK and several other European countries, where studies have found it is an effective way of treating — or at least managing — opioid addiction.

In a statement to PNN, Health Canada said it supports using diacetylmorphine to help create a safe drug supply for addicts who use dangerous street drugs and have failed at other forms of treatment.

“Many stakeholders have been calling for a secure and predictable supply of pharmaceutical-grade opioids as an alternative to the contaminated illegal drug supply. Studies have shown that prescription opioids, such as injectable hydromorphone and diacetylmorphine (prescription-grade heroin), have been successful in helping to stabilize and support the health of some patients with opioid use disorder,” said Jennifer Novak, Executive Director of Health Canada’s Opioid Response Team.

“Health Canada has taken steps towards this objective, including making prescription opioids used in the treatment of severe opioid disorder more easily accessible to healthcare practitioners, reducing regulatory barriers, funding guidelines for opioid use disorder treatment, and supporting safe supply pilot projects in British Columbia.”

Pain patients and their advocates bristle at Health Canada’s willingness to liberalize the use of heroin to treat addiction – while it supports policies that limit access to opioid pain medication.

"While it's necessary to make every effort to keep those suffering from substance abuse alive, why has this come at the cost of pain patients' lives? Health Canada blamed these patients for overdose deaths they played no part in and consequently they can no longer access their necessary medicine. The most severe have been sent spiraling back into more suffering, disability, suicide, and to purchase street drugs out of sheer desperation,” says Ann Marie Gaudon, a PNN columnist, pain patient and advocate. 

“Health Canada acts like a hero trying to save those addicted while simultaneously refusing to admit that they have indeed added to the death toll by adding pain patients. Where is their help? It is nowhere to be seen in the homes of Canada." 

Nearly 1 in 5 Canadians suffer from chronic pain and Canada has the second highest rate of opioid prescribing in the world.   

In an effort to reduce the supply of prescription opioids, Canada adopted an opioid guideline in 2017 that is very similar to one released by the U.S. Centers for Disease Control and Prevention a year earlier. Both guidelines have had a negligible impact on the overdose rate, while pain patients on both sides of the border lost access to opioid medication or had their doses reduced to ineffective levels.

“Health Canada recognizes that some people who live with chronic pain have been unable to access opioid medications when needed to manage their pain,” Novak said. “We know that opioid medications are an important tool in the management of pain for some Canadians and are working with stakeholders and partners to promote opioid prescribing practices that balance the benefits and harms of these medications based on the individual needs of each patient.” 

Asked what Health Canada is doing to improve healthcare for pain patients, Novak said the agency was providing $3 million in funding to improve education in pain management for physicians, nurses, pharmacists and social workers.  

Three million dollars is a tiny fraction of the $253 billion spent on healthcare in Canada in 2018.

"It's a pittance but the very sad part is that it's all going right back into the same people and programs that made this whole mess to begin with,” says Gaudon. “Nothing new, no help on the horizon for those whose lives have been shattered. They talk as if they are doing something but they truly are not. It's pure rubbish."

Should Heroin Be Used to Treat Addiction?

By Pat Anson, PNN Editor

Some Canadian doctors are using novel approaches to treat opioid addiction, everything from safe injection sites to opioid vending machines to prescription heroin.

A new proposal would take the concept a step further by establishing the first clinical guideline for using hydromorphone and pharmaceutical grade heroin to treat people with severe opioid use disorder. The idea is to provide a safer supply to opioid addicts who currently use illicit heroin, counterfeit pills and other street drugs, which are often laced with fentanyl.

"Offering injectable opioid treatments is an effective way for clinicians to address the toxicity of the fentanyl-adulterated drug supply and help people achieve stability so they can focus on other aspects of their lives to get well, such as housing, employment, and connecting with family," says Dr. Christy Sutherland, Medical Director of PHS Community Services Society in Vancouver, BC.

Sutherland is one of the co-authors of the guideline, which is published in the Canadian Medical Association Journal. In 2018, nearly 4,500 Canadians died from opioid overdoses, with about 75% of the deaths involving fentanyl, a synthetic opioid that’s become a scourge on the black market.

"Opioid use disorder is a public health emergency nationwide; unfortunately, resources for the treatment of opioid addiction have been scarce and guidelines outlining best practices for innovative treatments have been lacking. This guideline is a blueprint for health practitioners to step up and provide evidence-based care," says Dr. Nadia Fairbairn, British Columbia Centre on Substance Use and the University of British Columbia, Vancouver, BC.

Heroin is classified as a Schedule I controlled substance in the United States, making it illegal to prescribe. But pharmaceutical grade heroin (known as diacetylmorphine) is legal in Canada, UK and several other European countries.

Studies have found that heroin-assisted treatment is effective in treating opioid addiction in patients who have failed at other treatment methods, such as methadone.

Under the proposed guideline, injectable heroin (diacetylmorphine) and hydromorphone (Dilaudid) could be used to treat severe opioid addiction in patients who do not respond to oral medication or use illicit injectable opioids.

It would be up to each Canadian province to decide whether to adopt the guideline.

Pharmaceutical heroin and safe injection sites are controversial issues in the U.S. But a recent analysis by the RAND Corporation advocates their use to combat opioid addiction.

“Given the increasing number of deaths associated with fentanyl and successful use of heroin-assisted treatment abroad, the U.S. should pilot and study this approach in some cities,” said Beau Kilmer, co-director of the RAND Drug Policy Research Center. “This is not a silver bullet or first-line treatment. But there is evidence that it helps stabilize the lives of some people who use heroin.”

What About Pain Patients?

Pain patient advocates in Canada were taken aback by the proposal to liberalize the use of heroin to treat opioid addiction. Opioid pain medication is increasingly difficult to obtain in Canada, as it is in the United States, because of restrictive guidelines.

“It is indeed shocking. Pain patients continue to be marginalized, stigmatized, ignored and left to suffer,” said Barry Ulmer, Executive Director of the Chronic Pain Association of Canada.  “I do think it is ridiculous to say opioid use disorder is a public health emergency. The population they are addressing no doubt has to be addressed, but in terms of numbers it is minuscule to those suffering pain, yet the number of dollars expended for both is just out of whack.

“People suffering pain cannot obtain help or even maintain access to medication they have been stable on for years. Something is sadly wrong. What is a public health emergency is the epidemic of undertreated chronic pain. They should get their blinders off. We have well over 1 million Canadians suffering from high impact pain, yet they are pretty much marginalized.”

One of those Canadians is Dan Wallace, a retired military veteran and police detective who lives with chronic knee and shoulder pain.

“I applaud the efforts made and others that are contemplated for the near future that would allow those who are addicted to obtain legally prescribed heroin that would keep them from the tainted street drug supply,” Wallace said. “Where I have a problem is with the complete dismissal of medical care to the many legacy patients who were previously prescribed opioids to manage their pain.”

Wallace used opioid medication for over 20 years before being tapered. He now has trouble walking and sleeping because of what he calls “a tortuous and cruel degree of pain.”

“I and others like me aren’t looking for a handout of free heroin because we haven’t been able to control ourselves and have become addicts. No one deserves to be treated like throw-away patients yet pain patients are just that. Why is it that their lives matter while simultaneously ours do not?” Wallace asks.

“I have never abused any substance in my life. Does my suffering ever help a single person who will now be getting prescribed heroin so they don’t have to buy illegal street drugs? Health Canada should be deeply ashamed at the needless suffering, disability, and deaths of pain patients they have caused.”

The Opioid Risk Tool Has Been Weaponized Against Pain Patients

By Dr. Lynn Webster, PNN Columnist

I was surprised and deeply disappointed to learn this week that people have been denied opioid prescriptions due to their responses on the Opioid Risk Tool (ORT).

As a guest on the DPP Rally Talk Show with Claudia Merandi, I heard from a caller who told me that her doctor denied her an opioid prescription based on her ORT answers.

One particular answer seems to have caused the caller’s problem: She acknowledged her history of experiencing preadolescent sexual abuse. Apparently, the doctor used that as a reason to deny her access to opioid medication to treat her pain. This is a terrible misapplication of the tool.

The ORT is a self-assessment tool I developed and published about 15 years ago. It was developed at a time when we didn’t know the rate of opioid abuse in patients who were prescribed an opioid for noncancer pain. We needed a tool to help evaluate whether the risk of potential harm from opioids outweighed the good.

I never intended for doctors to use the ORT to determine who should or shouldn’t be prescribed an opioid. My goal was to help doctors identify patients who were at increased risk of misuse and addiction, so that they could receive more careful observation during treatment.

Since abuse and addiction are diagnosed by observing atypical behaviors, knowing which patients are at greatest risk for displaying those behaviors is useful in establishing appropriate levels of monitoring for abuse.

I was not alone in the belief that it was critical to assess patients for their risk potential.

In 2009, the American Pain Society and American Academy of Pain Medicine published a guideline for opioid prescribing. Its first recommendation stated: “Prior to initiating COT (chronic opioid therapy), clinicians should conduct a history, physical examination, and appropriate testing, including an assessment of risk of substance abuse, misuse, or addiction.”

Then, in 2016, the Centers for Disease Control and Prevention’s opioid-prescribing guideline recommended that “before starting and periodically during continuation of opioid therapy, clinicians should evaluate risk factors for opioid-related harms.”

Several other opioid prescribing guidelines also recommended assessing patient risk before initiating therapy. These included the Washington State Department of Health, Utah Clinical Guidelines on Prescribing Opioids for Treatment of Pain, the American Society of Interventional Pain Physicians (ASIPP) Opioid Guidelines, and others.

Risk Factors for Opioid Abuse

Assessing the risk of developing opioid abuse is based on genetic and environmental factors, just as it is with other diseases. Accordingly, the ORT includes questions about family and personal history of substance abuse, since both areas contribute to genetic and environmental factors. 

Genetics are estimated to contribute between 50 to 60% of an individual's vulnerability to opioid addiction. By contrast, genetics contribute only about 30% to a person's vulnerability to marijuana.

A person with one addiction is seven times more likely to develop an addiction to a different class of drugs, so genetics plays a major role in determining who will and who will not develop an opioid use disorder (OUD). Additionally, life experiences -- which are part of one’s environment -- also play a role.

The ORT asks if there is a history of experiencing preadolescent sexual abuse. Studies indicate that preadolescent sexual abuse is believed to result in something clinically similar to post traumatic stress disorder (PTSD).

The National Institute of Drug Abuse (NIDA) has reported that 30 to 60% of women who are undergoing drug abuse treatment suffer from PTSD. One treatment center in New York City reports that more than 90% of women treated for substance abuse had experienced sexual or traumatic abuse. 

According to another NIDA report, victims of rape were 10 times more likely to have abused heroin and other stimulants than the general population. A study in 2000 also showed that a history of preadolescent sexual abuse tripled the risk of drug use disorders.

Many other studies have corroborated these studies, showing that preadolescent sexual abuse is a risk factor for substance abuse later in life. The most important of these is the seminal CDC-Kaiser Permanente Adverse Childhood Experience Study.

A Cruel Misapplication of ORT

Environmental and genetic factors should influence how closely a patient's opioid use is monitored. However, a history of experiencing preadolescent sexual abuse does not mean a person will necessarily develop an OUD. It is only a risk factor. It does not determine the outcome of using opioids, although it may partially indicate the level of monitoring, support, and education that would be appropriate.

It is a cruel misapplication of the ORT to use a background of sexual abuse as the only criterion to assess whether a patient should receive opioid therapy. The ORT is an important tool in mitigating harm that prescribing opioids could cause. It should not be weaponized to justify denying people in pain appropriate therapy. 

Lynn R. Webster, MD, is a vice president of scientific affairs for PRA Health Sciences and consults with the pharmaceutical industry. He is author of the award-winning book, “The Painful Truth,” and co-producer of the documentary, “It Hurts Until You Die.” You can find him on Twitter: @LynnRWebsterMD. 

The information in this column 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.

Mother Who Lost Son to OxyContin Vindicated by Purdue Settlement

By Mark Kreidler, Kaiser Health News

In the 15 years since she lost her son to a single OxyContin pill, Barbara Van Rooyan has had but one up-close look at the people representing the company that made it.

It was in a small courthouse in Abingdon, Va., where Van Rooyan and other relatives of OxyContin victims gathered for a sentencing hearing in 2007. Three executives of Purdue Pharma had pleaded guilty to federal charges related to their misbranding and marketing of the powerful opioid. The company had pleaded guilty as well.

Van Rooyan and the others in her group spoke during the sentencing, giving voice to their grief and their pain. They wanted the executives sent to jail for knowingly expanding an opioid crisis fast engulfing the country.

Instead, Purdue paid fines totaling $634 million. The executives served no time. The company was allowed to continue aggressively marketing its product, and the following year, sales of OxyContin reached $2 billion.

From 1999 to 2017, more than 700,000 people in the U.S. died of drug overdoses, according to the Centers for Disease Control and Prevention. In 2017, nearly 68% of the more than 70,000 recorded overdose deaths involved opioids, mostly illicit opioids such as fentanyl and heroin.

“I never really thought a whole lot about evil before this all happened,” Van Rooyan said recently, seated on a couch in the living room of her Irvine, Calif., home. “But to see this kind of malevolence or disregard for human life — I don’t know what else to call it but evil.”

The outcome in that Virginia courthouse was a far cry from last week’s news of a tentative mass settlement of many of the 2,000-plus lawsuits against the company, which could total upward of $12 billion and result in Purdue’s dissolution.

The potential settlement amount would include $3 billion from the Sackler family, owners of Purdue, whose fortune is estimated at $13 billion. The family has amassed that money over the past two decades, largely by selling OxyContin, an opioid painkiller.

‘The Lid Is Off’

Van Rooyan’s Purdue experience is a story of deception, sadness and frustration — yet when she tells it now, she emits a surprising spark of energy. That’s because Van Rooyan, part of the unlikely group of citizens who repeatedly took flailing swings at Purdue Pharma, is watching the giant fall.

Van Rooyan, who has studied the cases against Purdue closely, sees the paradox in the proffered settlement: Much of the payout would be financed by profits from the continued sale of OxyContin, under a new company that would be formed following a Chapter 11 bankruptcy.

But in some regard, she said, Purdue Pharma’s complicity in the opioid crisis has finally emerged into the general public’s view. “The world really knows now. They get it,” she said. “The lid is off, and all this stuff is bubbling out.”

That wasn’t the case on the night of July 4, 2004, when Van Rooyan and her husband, Kirk, got the call that changed their world. Barbara, then a professor of counseling at Folsom Lake College near Sacramento, was told that her son, Patrick Stewart, lay in a San Diego hospital, in a medically induced coma from which he was unlikely to emerge.

Patrick, a graduate of Oak Ridge High School in El Dorado Hills, Calif., and San Diego State University, died at age 24.

His friends told Barbara they had attended an Independence Day party at which someone offered her son an OxyContin pill, telling him it “was kind of like a muscle relaxant and it was FDA approved, so it was safe,” she said. Patrick, who had also consumed a couple of beers, was opioid intolerant and suffered respiratory failure in his sleep.

Barbara Van Rooyan holds picture of her son, Kirk

“At the time,” Van Rooyan said, “all I knew about Oxy was that Rush Limbaugh had been addicted to it.”

She was about to learn a lot more.

OxyContin Abuse

Van Rooyan channeled her grief through intense research into Oxy’s vast potential for damage despite the company’s sales pitches to the contrary. A slow-release pain treatment with a heavy dose of the narcotic oxycodone, it could be easily crushed or dissolved for a more intense and addictive high. Rampant abuse already had begun to be reported, particularly in the Appalachian area, author Beth Macy wrote in her national bestseller “Dopesick.”

Later in 2004, Van Rooyan found Ed Bisch, a Philadelphia man who had begun a website to expose Oxy abuse in the wake of his teenage son’s death. The following year, Van Rooyan and her husband, a plastic surgeon, petitioned the Food and Drug Administration to require that OxyContin be made more abuse-resistant, and that its use be strictly limited to severe pain.

“This was an exhausting process, which she and Kirk did as a labor of love to try to save others,” Bisch recalled.

Van Rooyan became the California arm of a grassroots movement known as RAPP — Relatives Against Purdue Pharma. The group, originally just four in number, protested at physician meetings funded by pharmaceutical companies and testified before Congress. Van Rooyan enlisted the help of U.S. Sen. Dianne Feinstein (D-Calif.), who wrote the FDA on her behalf and later sent Van Rooyan a letter of commendation.

But most members of Congress did not reply to Van Rooyan’s letters, she said. The FDA said its review needed more time — which turned out to be eight years. By then, Purdue already had reformulated OxyContin to make it more abuse resistant and to renew its patent, but the FDA declined to restrict its use to managing severe pain.

Van Rooyan pressed on, but for a long while, the opioid crisis felt to her like a topic hiding in plain sight. And fighting Purdue while still grieving the loss of son Patrick was taking a toll.

“Her determination was tireless,” Bisch said, “but eventually the frustration burned us out.”

And then came the turn.

A rash of high-profile opioid overdoses and deaths, from actor Heath Ledger to Tom Petty to Prince, put the topic squarely in the public eye — and 15 years after the death of Van Rooyan’s son, Purdue Pharma and other drugmakers were suddenly on the run.

(Editor’s note: Ledger, Petty and Prince all died from a lethal mix of opioids and other drugs that were apparently obtained on the street.)

Wants Purdue Settlement Spent on Treatment

Van Rooyan tracks every development related to Purdue, including a lawsuit in New York that alleges members of the Sackler family have been offloading their fortunes into private or offshore accounts to shield them from a settlement.

But she’s not out for vengeance. Her goals have changed.

“Do I want the records to be public? Do I want these people to have their business shut down? Yes, I do,” she said. “But more than vindictiveness, I want that money of theirs to go to treatment and rehab. If that happens, something good can come out of it.”

If she has a regret, it is that the case in Virginia ended in 2007 with no more than a fine. “If that result had been different — if people had gone to jail — it could have changed the trajectory of this,” she said.

Ana Venegas for KHN

But momentum finally appears to be gathering, and Van Rooyan finds herself identified as one of the trailblazers of the anti-OxyContin movement. She spends little time dwelling on that. Instead, she quotes her younger son, Andrew, who told her, “We didn’t want any of this — this is just the hand we were dealt. We need to play the cards the best we can.”

“She’s just a really strong person,” said Kirk Van Rooyan, who has been with Barbara throughout the ordeal, though he is not Patrick’s biological father. “There have been times when I’d think to myself, ‘How would I be doing if I were in her shoes?’ And the answer usually is, ‘Not as well as she’s doing.’”

Van Rooyan, a longtime artist, now spends much of her time volunteering with veterans in Orange County, Calif., helping them get back into the workforce and using art therapy to help them express themselves.

The art is special to Van Rooyan, she said, because it is part of what saved her in the aftermath of her son’s death.

“Patrick was the one who suggested I take my first class,” she said. After a few delays, she finally enrolled. It was about a month before that Fourth of July in 2004.

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of the Kaiser Family Foundation, which is not affiliated with Kaiser Permanente.

One in Four Adults in England Take Addictive Meds

By Pat Anson, PNN Editor

Nearly 12 million people – about one in four adults in England -- are taking addictive prescription drugs to treat depression, anxiety, insomnia or chronic pain, according to a new review by Public Health England (PHE).

The review takes a cautionary view on the use of five drug classes – opioids, antidepressants, benzodiazepines, gabapentinoids, and so-called “z-drugs” such as zolpidem, zopiclone and zaleplon.

“The medicines we looked at help to make millions of people every year feel better and recover from their illness. Doctors can prescribe them because there is good evidence that they work, but they do have some risks,” the PHE report found.

Benzodiazepines, z-drugs, opioids and gabapentinoids are associated with dependence and withdrawal, while there’s a risk of withdrawal with antidepressants. When the drugs are taken in combination or in high doses, there is also risk of respiratory depression and overdose.  

About half the patients prescribed the drugs in England had been taking them for at least a year — a sign of dependence. But the report cautions doctors not to abruptly discontinue the drugs and to taper them gradually, if at all.

“There is a view that a sub-population of chronic pain patients can be prescribed long-term opioids at relatively stable doses so that their analgesia and functioning can be maintained with good adherence and tolerable side-effects,” the report found.

“We do not want to put anyone off safely using medicines that could help them. Stopping or limiting the use of medicines could also cause harm, including increasing the risk of suicide or making people try to get medicines or illegal alternatives from less safe sources, such as illegal websites or drug dealers.”

Increasing Use of Antidepressants and Gabapentinoids

Antidepressants were prescribed to about 7.3 million people in England or 17% of the adult population. Opioids were prescribed to 5.6 million patients, followed by gabapentinoids (1.5 million), benzodiazepines (1.4 million) and z-drugs (1 million). Prescriptions for opioids, benzodiazepines and z-drugs are dropping, while the use of antidepressants and gabapentinoids is growing. 

Gabapentinoids such as pregabalin (Lyrica) and gabapentin (Neurontin) were originally developed to treat epilepsy, but the drugs are increasingly prescribed in the UK to treat neuropathy and other types of chronic pain. PHE researchers found only marginal evidence that they are effective for pain and alarming signs that they are being misused. 

“Gabapentinoids have come to be used for a wider range of indications than is supported by the evidence or their licensing, and they have sometimes been prescribed in place of opioids or benzodiazepines in the likely-mistaken belief that they are less liable to misuse or dependence, and lack of awareness of the withdrawal problems that can arise when prescribing is stopped,” the report said. 

Prescriptions for opioids and gabapentinoids were 1.6 times higher in parts of England with more poverty. People in poor areas are also more likely to be prescribed medicines for longer periods. Prescription rates for women are about 1.5 times higher than for men. Prescription rates also increased with age.

Outcomes Matter When Opioids Are Tapered

By Roger Chriss, PNN Columnist

The drug overdose crisis has led to a rethinking of pain management. Prescription opioids are now seen as risky medications with potentially serious side effects, including addiction and overdose. As a result, there is an increasing push to discontinue or taper patients on long-term opioid therapy.

A recent op/ed in the Annals of Internal Medicine by physicians Roger Chou, Jane Ballantyne and Anna Lembke claims there is “little benefit” from long-term opioid use and “many patients” would benefit from tapering. They even suggest that the use of addiction treatment drugs such as Suboxone should be expanded to include pain patients dependent on opioids.

“Evidence indicates that long-term opioid therapy confers little benefit versus nonopioid therapy, particularly for function. Opioid use disorder (OUD) occurs in a subset of patients, and quality of life may be adversely affected despite perceived pain benefits,” they wrote.

“We argue that achieving effective, safe, and compassionate tapers requires implementing and incentivizing tapering protocols, recognizing prescription opioid dependence as a distinct clinical condition necessitating treatment, and expanding the indication for buprenorphine formulations approved for OUD to include prescription opioid dependence.”

It should be noted Chou is one of the co-authors of the CDC’s controversial opioid prescribing guideline, while Ballantyne and Lembke are board members of the anti-opioid activist group Physicians for Responsible Opioid Prescribing (PROP). Ballantyne, who is president of PROP, was part of the “core expert group” that advised the CDC when it was drafting its guideline.

What Happens to Tapered Patients?

The goal of improving patient safety is admirable. However, there is relatively little data on what happens to patients during tapering or after opioids are discontinued. The evidence is mixed at best.

A 2018 review in Pain Medicine of 20 studies involving over 2,100 chronic pain patients found that most patients had less pain or the same amount of pain when tapering was completed. But the studies were not controlled and the evidence was of marginal quality, with large amounts of data missing.

A 2019 study in the journal Pain evaluated outcomes in 49 former opioid users with chronic pain. The findings showed that about half the patients reported their pain to be better or the same after stopping opioids, while the other half reported their pain was worse.

There are risks associated with tapering that also need to be considered, such as uncontrolled pain, suicide, overdose and early death. The tapering process itself can be extremely challenging and patient outcomes after discontinuation are not necessarily positive.

A recent study in the Journal of General Internal Medicine looked at what happened to chronic pain patients being treated at a large urban healthcare system in the year after they were tapered.

For about 5 percent of patients, “termination of care” was the primary outcome – a vague category that means there was no record of them seeking further treatment. Some of those patients may have miraculously gotten better and required no healthcare. And some may have died.

“These findings invite caution and demonstrate the need to fully understand the risks and benefits of opioid tapers,” the authors warned.

Another study in the same journal is also concerning. Researchers at the University of Washington followed 572 patients who were treated with opioids at a Seattle pain clinic. About 20 percent of the patients died, a high mortality rate, but the death rate was even higher for patients who were tapered. Seventeen of them died from a definite or possible overdose.

“In this cohort of patients prescribed COT (chronic opioid therapy) for chronic pain, mortality was high. Discontinuation of COT did not reduce risk of death and was associated with increased risk of overdose death,” the authors concluded.

"We are worried by these results, because they suggest that the policy recommendations intended to make opioid prescribing safer are not working as intended," said lead author Jocelyn James, assistant professor of general internal medicine at the University of Washington School of Medicine. "We have to make sure we develop systems to protect patients."

In other words, opioid discontinuation does not necessarily lead to better outcomes, as Chou, Ballantyne and Lembke suggest. The blind push to taper patients at all costs to reduce opioid prescribing can have tragic consequences — which no one seems to be tracking.

“Crucially, today’s opioid prescribing metrics take no count of whether the patient lives or dies. Data from two recent studies strongly suggest it is time to start counting. The sooner quality standards are revised in favor of genuine patient protection, the better,” says Stefan Kertesz, MD, an Alabama physician and researcher.

Outcomes matter. And they need to be reasonable for the patient. A person with a self-limiting condition like low back pain may well benefit from opioid discontinuation. But some patients with more chronic conditions do not get better, and their needs cannot go ignored.

The Canadian Psychological Association emphasizes caution and patient safety in a recent position paper on the opioid crisis:  “Tapering must always be done gradually under physician or nurse practitioner supervision, with the patient's consent, and with ongoing support and monitoring of pain and functioning, as well as management of withdrawal symptoms."

The use of prescription opioids should always take patient risks and benefits into consideration. It also requires knowing about outcomes when taking patients off opioids. At present there is too much interest in numbers and too little interest in people.

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.

Opioid Overdoses Drop, But Fentanyl Crisis ‘Likely to Get Worse’

By Pat Anson, PNN Editor

Opioid overdose deaths fell by nearly 5 percent in 25 U.S. states last year, according to a new analysis from the Centers for Disease Control and Prevention -- one of the first reports to document a significant decrease in opioid overdoses.

The 25 states covered in the report are participating in the CDC’s State Unintentional Drug Overdose Reporting System (SUDORS), which tracks overdose deaths through toxicology, medical examiner and coroner reports. SUDORS is considered more reliable than other databases because it provides more details on the types of drugs involved – both legal and illegal.

Opioid overdoses fell overall by 4.6% in the first six months of 2018, driven in large part by a 6.6% decline in deaths involving prescription opioids. The CDC found that less than a third (28.7%) of the overdoses were linked to opioid pain medication. Most overdoses involve illicit drugs.

“Prescription opioid deaths stabilized nationally from 2016 to 2017, and the number of opioid prescriptions filled has been decreasing for several years, as efforts to reduce high-risk prescribing have increased. Findings from this report suggest these efforts might have fostered decreases in prescription opioid deaths without illicit opioids,” researchers said.

While the data about prescription opioids is encouraging, the report paints a grim picture about the abuse of other substances. Nearly 63% of the opioid overdoses involved a non-opioid drug such as cocaine, methamphetamine or benzodiazepines.

Overdoses linked to illicitly manufactured fentanyl (IMF) rose by 11.1% in 2018, with fentanyl or a fentanyl analog involved in nearly nine out of ten opioid deaths.

Fentanyl is a synthetic opioid 50 to 100 times more potent than morphine. Fentanyl analogs such as carfentanil can be even stronger. Most drug users have no idea what they’re getting, because fentanyl is often added to heroin, cocaine and other drugs to boost their potency, or used in the production of counterfeit medication.

Fentanyl Dominates Black Market

A new report from the RAND corporation, a nonprofit research organization, suggests the fentanyl problem will be hard to eradicate. Researchers looked at synthetic opioid markets in the U.S. and other parts of the world, such as Canada and Estonia — where fentanyl first appeared 20 years ago..

“Once fentanyl gains a foothold, it appears capable of sweeping through a market very quickly,” wrote Bryce Pardo, lead author of the study and an associate policy researcher at RAND. “We know of no instance in which fentanyl attained a dominant position in the marketplace and then lost that position to another less potent opioid. To date, fentanyl’s spread appears to be a one-way ratchet.

“One of the most important — and depressing — insights in this analysis is that however bad the synthetic opioid problem is now, it is likely to get worse before it gets better.” 

RAND researchers say the surge in fentanyl and other synthetic opioids is driven by supply-side factors more than user demand. China's pharmaceutical and chemical industries are poorly regulated, allowing producers to cheaply produce fentanyl and ship it to buyers anywhere in the world. Mexican drug traffickers smuggle most of the fentanyl that enters the U.S., although some of it is shipped in the mail or by commercial delivery services.

DEA IMAGE

Unconventional strategies may be needed to address the fentanyl crisis. The RAND researchers advocate several innovative approaches, such as supervised drug consumption sites, creative supply disruption, drug product testing, and heroin-assisted treatment, which is available in some countries. Sweden has developed an online market with fentanyl analogs sold primarily as nasal sprays.

"It might be that the synthetic opioid problem will eventually be resolved with approaches or technologies that do not currently exist or have yet to be tested," said Beau Kilmer, study co-author and director of the RAND Drug Policy Research Center. "Limiting policy responses to existing approaches will likely be insufficient and may condemn many people to early deaths."

RAND researchers say there is little reason to believe that tougher sentences, including homicide laws for low-level drug dealers and couriers, will make a difference.

Last week the Mexican navy found over 25 tons of powdered fentanyl on a Danish ship docked at a Mexican port, one of the largest fentanyl shipments ever seized. The shipment originated from Shanghai, China.

Chinese officials are pushing back on claims that they’re not doing enough to stop fentanyl exports, saying the U.S. needs to stop blaming other countries for its own drug problems.

“A small group of people produce fentanyl illegally in China and mail them to the U.S. and other regions, driven by the exorbitant profit and at the request of criminals overseas, including those in the U.S. The Chinese government has zero tolerance for this. Once we find clues, we chase them down and spare no one,” Liu Yuejin, deputy head of the China National Narcotics Control Commission, told Bloomberg.

“I think the most important thing for U.S. politicians is to face the reality: What’s the root cause of such large-scale abuse of fentanyl in the U.S.? They need to find out and come up with solutions.”