Studies Warn of Pregabalin Deaths

By Pat Anson, Editor

Two new studies – one in Canada and one in Australia – should give pause to patients who use opioids and pregabalin (Lyrica), an anticonvulsant medication increasingly prescribed for fibromyalgia, neuropathy and other chronic pain conditions. Both studies found a number of overdose deaths that involve – but were not necessarily caused -- by pregabalin.

The Canadian study, published in the Annals of Internal Medicine, looked at over 1,400 patients in Ontario on opioid medication from 1997 to 2016 who died from opioid-related causes. Another group of over 5,000 surviving opioid patients was used as a control group.

Researchers found that patients who were co-prescribed opioids and pregabalin had a significantly higher risk of an overdose.

The risk of death was over two times higher for patients receiving opioids and a high dose of pregabalin (over 300mg) compared to those who took opioids alone.

Patients on a low or moderate dose of pregabalin also had a heightened risk, although not as large.

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Researchers say pregabalin has a sedative effect and may interact with opioids in ways that increase respiratory depression. Few doctors and patients are aware of the risk, even though over half of Ontario residents who begin pregabalin therapy are also prescribed an opioid.

"There is an important drug interaction between opioids and pregabalin that can lead to increased risk of fatal overdose, particularly at high doses of pregabalin," lead author Tara Gomes, PhD, of the Institute for Clinical Evaluative Sciences (ICES) and St. Michael's Hospital in Toronto, told MedPage Today.

"Clinicians should consider carefully whether to prescribe opioids and pregabalin together. If they decide that both medications are clinically appropriate, they should start with low doses and monitor their patients closely."

Lyrica (pregabalin) and Neurontin (gabapentin) are both made by Pfizer and belong to a class of anticonvulsant nerve medication called gabapentinoids. Sales of gabapentinoids have tripled in recent years, in part because of CDC prescribing guidelines that recommend the drugs as alternatives to opioid medication.  

U.S. health officials have only recently started looking into the misuse and abuse of gabapentinoids, which are increasingly used by addicts to enhance the euphoric effects of heroin and other illicit opioids. While gabapentin  has a warning label cautioning users who take the drug with opioids, there is no similar warning for pregabalin.

“Although current product monographs for gabapentin contain warnings about serious adverse events when this agent is combined with opioids, those for pregabalin do not. The importance of our finding warrants a revision of the pregabalin product monographs,” wrote Gomes.

Pregabalin Abuse in Australia

Health officials in Australia are also concerned about the growing use of pregabalin.  Researchers at the NSW Poisons Information Centre say poisoning cases involving pregabalin rose from zero in 2005 to 376 cases in 2016.

“Our study shows a clear correlation between the rapid and continuous rise of pregabalin dispensing and an increase in intentional poisonings and deaths associated with pregabalin,” said lead author Dr. Rose Cairns, a specialist at the NSW Poisons Information Centre.

According to the Australian Journal of Pharmacy (AJP), there have been 88 recorded deaths associated with pregabalin in recent years. Most of the deaths involved young, unemployed males who had a history of substance abuse, particularly with opioids, benzodiazepines, alcohol and illicit drugs.

“We believe that Australian doctors may not be aware of the abuse potential of pregabalin,” Cairns said. “Most patients who are prescribed this medication are in the older population but the group who are at high risk of overdosing are much younger. These people are likely to have been prescribed pregabalin despite having a history of substance abuse.”

According to researchers, up to two-thirds of people who intentionally misused pregabalin had a prior documented substance abuse history. “Prescribers need to consider this growing body of evidence that pregabalin has abuse potential before prescribing, especially to patients with substance abuse history,” said Cairns.

Pfizer did not respond to a request for comment on the Canadian and Australian studies.

Did 70,000 Opioid Deaths Go Uncounted?

Pat Anson, Editor

The nation’s overdose epidemic may be worse than it appears, according to a new study that estimates as many as 70,000 opioid-related overdose deaths since 1999 were not included in mortality figures because of incomplete reporting.

The study, which does not distinguish between deaths involving prescription opioids and those linked to illegal opioids such as heroin, adds to growing evidence that the government's overdose statistics are unreliable.

Researchers at the University of Pittsburgh Graduate School of Public Health analyzed death certificate data from 1999 to 2015 and found that coroners and medical examiners in many states often did not specify the drug that contributed to the cause of death.  

“Coroners are less likely than medical examiners to be physicians and do not necessarily have the medical training needed to complete drug information for death certificates based on toxicology reports,” said lead author Jeanine Buchanich, PhD, who reported the findings in Public Health Reports, the official journal of the Office of the U.S. Surgeon General.

"Incomplete death certificate reporting hampers the efforts of lawmakers, treatment specialists and public health officials. And the large differences we found between states in the completeness of opioid-related overdose mortality reporting makes it more difficult to identify geographic regions most at risk."

The variability among states was significant - ranging from fewer than 10 unspecified overdose deaths in Vermont to 11,152 in Pennsylvania. States with a decentralized county coroner system or a hybrid system that uses both coroners and medical examiners were more likely to have a high proportion of unspecified overdose deaths.

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Overdose deaths are assigned specific "T codes" for each drug found by the coroner or medical examiner. Deaths that can’t be attributed to a specific drug are given the T-code of T50.9 – which means "unspecified drugs, medicaments and biological substances."

Researchers say the widespread use of that code underestimates the actual number of opioid-related deaths. In five states - Alabama, Indiana, Louisiana, Mississippi and Pennsylvania - more than 35 percent of the overdose deaths were coded as unspecified.

“Our analyses indicated that potentially more than 70,000 unspecified, unintentional overdose deaths in the past 17 years, including more than 5,600 in 2015, could be categorized as opioid-related unintentional overdose deaths,” said Buchanich.

Questionable Overdose Data

Last year President Trump’s opioid commission urged the federal government to work with states to improve the toxicology data on overdose deaths by developing uniform forensic drug testing.

“We do not have sufficiently accurate and systematic data from medical examiners around the country to determine overdose deaths, both in their cause and the actual number of deaths,” the commission said in its final report.

Critics also say the overdose data reported by the CDC and other federal agencies is often flawed or cherry-picked. CDC recently researchers admitted that many overdoses involving illicit fentanyl and other synthetic black market opioids were erroneously counted as prescription opioid deaths. Toxicology tests cannot distinguish between pharmaceutical fentanyl and illicit fentanyl

The overdoses data is further muddied because multiple drugs are involved in almost half of all drug overdoses. And there is no way to distinguish between deaths caused by legitimate opioid prescriptions and those caused by diverted prescriptions or counterfeit drugs.

A recent report from the Substance Abuse and Mental Health Services Administration found that drugs used to treat depression, anxiety and other mental health conditions are now involved in more overdoses than opioid pain medication.

The CDC estimates that 63,632 Americans died from drug overdoses in 2016 – a 21.5% increase over the 2015 total.  

How the DEA Changed the Overdose Numbers

By Pat Anson, Editor

The Drug Enforcement Administration has released its annual report on the threat posed to the U.S. by drug trafficking and the abuse of illicit drugs.

The 2017 National Drug Threat Assessment (NDTA) has both good and bad news about the nation’s worsening overdose crisis. But like other federal agencies, the DEA has a disturbing tendency to massage statistics to make the role of opioid pain medication more significant than it actually is.

“The threat posed by controlled prescription drug (CPD) abuse is prevalent. Every year since 2001, CPDs, specifically opioid analgesics have been linked to the largest number of overdose deaths of any illicit drug class, outpacing those for cocaine and heroin combined,” the report declares.

That sure makes it sound like opioid pain medication is killing more people than ever before, doesn’t it? A closer look at the numbers and methodology used by the DEA suggests otherwise.

"Controlled prescription drugs" is a very broad category that includes not only opioid pain relievers, but anti-anxiety drugs (Valium, Xanax), stimulants (Adderall, Ritalin), and anabolic steroids. And there's plenty of evidence people are dying from those drugs as well.

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This is not the first time the DEA has lumped opioid pain relievers with other drugs. In the 2016 NDTA, the DEA combined opioids with anti-anxiety drugs, but not stimulants or steroids.

A year earlier, in the 2015 NDTA, prescription opioids were in a category all to themselves.

The effect of these changing and broadening definitions is significant. Every year the overdose crisis appears to be getting worse and worse. It certainly is for deaths linked to illicit drugs like heroin, cocaine and fentanyl, but not necessarily for prescription drugs and definitely not for opioid pain medication.

One has to wonder why these definitions keep changing and distorting the true nature of the overdose crisis. Don’t take my word for it. Look at how the overdose numbers for "Selected Illicit Drugs" in 2013 have grown over the years.

In the 2015 NDTA, the DEA reported that an “opioid analgesic” was involved in the deaths of 16,235 Americans in 2013.

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In the 2016 NDTA, the DEA reported that “prescription drugs” were involved in the deaths of 22,767 Americans in 2013.

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And in the 2017 NTDA, the DEA reported that “medications” were involved in the deaths of 24,536 Americans in 2013. The "medications" category includes not only controlled prescription drugs, but over-the-counter drugs as well.

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Simply by changing the way they counted overdoses, the DEA and other federal agencies raised the death toll for 2013 by over 8,300 people.  We’re only using 2013 as an example.  From one report to the next, overdoses grew for every other year as well.

This isn’t the first time the federal government has played around with the overdose numbers. As PNN reported, last December the CDC and the White House Office of National Drug Control Policy released three different estimates of how many Americans died in 2015 from overdoses linked to prescription opioids.  

Within one week, the overdose numbers evolved from 17,536 deaths, down to 12,700, and then back up to 15,281 deaths. To use a football metaphor, that is known as moving the goalposts.

Pain Medication Abuse Declining

A closer reading of the 2017 NDTA shows that heroin, illicit fentanyl and other illegal drugs are now driving the overdose crisis, not opioid pain medication. Less than one percent of legally prescribed opioids are being diverted to the black market. 

A recent survey of law enforcement agencies, known as the National Drug Threat Survey, found that less than 10 percent of respondents nationwide believed controlled prescription drugs were the greatest drug threat in their jurisdiction -- down considerably from 2014 when over 21.5 percent reported the same

The abuse of prescription opioids is also declining. Fewer Americans are testing positive for hydrocodone, oxycodone and other painkillers in workplace drug tests. And the number of people seeking treatment for abusing pain medication has fallen significantly. From 2011 to 2014, admissions to publicly-funded treatment facilities for prescription opioid abuse fell by nearly a third. 

“This decline can in part be attributed to CPD (controlled prescription drugs) abusers switching to heroin or other illicit opioids. Some CPD abusers, when unable to obtain or afford CPDs, begin using heroin as a cheaper alternative offering similar opioid-like effects,” said the DEA.

“Expansion of the counterfeit pill market, to include pills containing fentanyl, threatens to circumvent efforts by law enforcement and public health officials to reduce the abuse of opioid medications; the arrival of large amounts of counterfeit prescription drugs containing fentanyl on the market replaces opioid medications taken off of the street.”

Curiously, the DEA report doesn’t even list kratom as a drug threat – even though the agency considers the herbal supplement a “drug of concern” and tried to ban it last year. 

“I think that all of us in the kratom community have a hard time reconciling the lack of a threat listing for kratom and yet still being considered a drug of concern,” said Dave Herman, chairman of the American Kratom Association, a pro-kratom consumer group.  “The science tells us that kratom has a low potential for either abuse or addiction and we hope to see that reflected in all DEA materials.”

Whether its kratom or pain medication, the DEA and other federal agencies have a responsibility to be consistent and to get their facts right.  Inflating the overdose numbers and blaming opioid medication may make for good headlines, but it diverts funding, resources and policymakers away from other drug problems that truly need more attention. We'll never get a handle on the overdose crisis if we keep moving the goalposts.

A recent editorial in the Journal of Pain Research took the CDC to task for doing just that.

"Transparency, freedom from bias, and accountability are, in principle, hallmarks of taxpayer-funded institutions. Unfortunately, it seems that at least one institution, the Centers for Disease Control and Prevention, continues to struggle with all three," wrote researchers Michael Schatman, PhD, and Stephen Ziegler, PhD.

"What began with a prescribing guideline created in secrecy has now evolved to the use of statistical data and public statements that fail to capture not only the complexity of the problem but also the distinction between licit and illicit opioids and their relationship to the alarming increase in unintentional overdose. This is unfortunately consistent with Mark Twain’s assertion that 'there are lies, there are damn lies, and then there are statistics.'"

Report Finds ‘Rush to Judgment’ in Kratom Deaths

By Pat Anson, Editor

Medical examiners in New York and Florida made significant errors when they attributed the recent deaths of two young men to the herbal supplement kratom, according to a new analysis commissioned by the American Kratom Association, a pro-kratom consumer group.

At issue are the sudden deaths of Matthew Dana in upstate New York in August and Christopher Waldron in Hillsborough County, Florida in July. Both men were 27.

A medical examiner listed Waldron’s cause of death as “intoxication by Mitragynine,” one of the active ingredients in kratom. The coroner who performed the autopsy on Dana blamed his death on a hemorrhagic pulmonary edema (blood in the lungs) caused by high levels of kratom.

“In both of these cited cases, the conclusions reported by the coroner and medical examiner citing ‘kratom overdose’ and ‘kratom intoxication’ appear to add to the long list of mistaken, inaccurate, and now discredited reports implicating kratom,” wrote Jane Babin, PhD, a molecular biologist and lawyer.

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“These two cases, where it appears there was a rush to judgment to align with a political narrative promoted by the Drug Enforcement Administration on kratom use, undermine the credibility of the search for the actual cause of death for the benefit of the decedent’s family and the public.”

Babin said mitragynine has never been found to cause a pulmonary edema, and the medical examiner erred in not analyzing Dana’s blood for drugs such as anti-anxiety medication or anabolic steroids. Dana was a police sergeant and bodybuilder, who reportedly used steroids as part of his bodybuilding program.

Babin said the medical examiner in Florida also “rushed to judgement” in blaming Waldron’s death on kratom. Two prescription medications used to treat depression and muscle spasms, Citalopram and Cyclobenzaprine, were also found in Waldron’s blood. Labels on both drugs warn they can cause coma or death when taken together. Waldron also had ventricular hypertrophy, an enlarged liver and thyroid disease, which may have contributed to his death, according to Babin’s report.

“What I see here are very troubling indications that these deaths may have been incorrectly attributed to kratom in the face of other causes, including possible anabolic steroid use in one case and contraindicated prescription medication interactions that could kill on their own,” said Karl Ebner, PhD, a toxicologist who reviewed the report.

“These families are owed the best evidence about what happened to their loved ones, not what would appear to be some conclusions that are incompletely supported by the current evidence."

Millions of people use kratom to treat chronic pain, depression, anxiety and addiction. Last year, the DEA attempted to list kratom as a Schedule I controlled substance, which would have made it a felony to possess or sell. The DEA said kratom was linked to several deaths, as well as psychosis, seizures and an increased number of calls to poison control centers  

The DEA suspended its plan after an outcry and lobbying campaign by kratom supporters.

"Last year, the DEA tried to demonize kratom. In 2017, the kratom community finds itself in the same situation all over again,” said David Herman, chair of the American Kratom Association (AKA). “This time, we are being told that two deaths were supposedly the result of kratom use.  Let me be very clear about this:  We do not believe that kratom caused these deaths.  That's what the science tells us.

“Given that there are millions of kratom consumers in the U.S., if this botanical was dangerous it would stand to reason that there would be thousands … or even tens of thousands of deaths … and that is absolutely not the case."

The AKA backed another study last year that found kratom has little potential for abuse and dependence. Most kratom users say the herb has a mild analgesic and stimulative effect, similar to coffee.

CDC Releases More Faulty Research About Opioids

By Pat Anson, Editor

A new study by researchers at the Centers for Disease Control and Prevention estimates that opioid overdoses have shaved two and a half months off the average life span of Americans – a somewhat misleading claim because the study does not distinguish between legally obtained prescription opioids and illegal opioids like heroin and illicit fentanyl.

The research letter, published in the medical journal JAMA, looked at the leading causes of death in the U.S. from 2000 to 2015. Overall life expectancy rose during that period, from 76.8 years in 2000 to 78.8 years in 2015, largely due a decline in deaths from heart disease, cancer, stroke, diabetes and other chronic health conditions.

But deaths due to Alzheimer’s disease, suicide, liver disease, drug poisoning and opioid overdoses rose, collectively causing a loss of 0.33 years in life expectancy – most of it due to opioids.

“This loss, mostly related to opioids, was similar in magnitude to losses from all the leading causes of death with increasing death rates,” wrote lead author Deborah Dowell, MD, of the CDC’s National Center for Injury Prevention and Control.

“U.S. life expectancy decreased from 2014 to 2015 and is now lower than in most high-income countries, with this gap projected to increase. These findings suggest that preventing opioid related poisoning deaths will be important to achieving more robust increases in life expectancy once again.”

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Dowell was also one of the lead authors of the CDC’s 2016 opioid prescribing guidelines, which discourage physicians from prescribing opioids for chronic pain. She and her two co-authors in the JAMA study --  both of them CDC statisticians -- do not explain why they failed to distinguish between black market opioids and legal prescription opioids, a dubious use of statistics akin to lumping arsonists in the same category as smokers or Boy Scouts learning to build campfires.  

They also fail to even mention the scourge of heroin and illicit fentanyl sweeping the country, which now accounts for the majority of opioid overdoses in several states.  

But Dowell and her co-authors don't stop there. The say the actual number of deaths caused by opioids is “likely an underestimate” because information on death certificates is often incomplete and fails to note the specific drug involved in as many as 25% of overdose deaths. This is another disingenuous claim, because it fails to explain why the data on the other 75% of overdoses is faulty too. 

Epidemic of Despair

Other researchers have also tried to explain the disturbing decline in American life expectancy – which began over adecade ago for middle-aged white Americans. Princeton researchers Anne Case and Angus Deaton were the first to document that trend,  when they estimated that nearly half a million white Americans may have died early because of depression, chronic pain, suicide, alcohol and drug abuse, and other health problems – an epidemic of despair linked to unemployment, poor finances, lack of education, divorce and loss of social connections.

The evidence was right there for Deborah Dowell and her co-authors had they looked for it. The JAMA study found that over 44,000 Americans committed suicide in 2015, a 66% increase from 2000, and over 40,000 died from chronic liver disease or cirrhosis, another 66% increase. Opioid overdoses during that same period rose to 33,000 deaths. 

Which is the bigger epidemic?

As PNN has reported, the CDC ignored early warnings from its own consultant that the agency’s opioid guidelines were being viewed as “strict law rather than a recommendation,” causing many doctors to stop prescribing opioid pain medication. Chronic pain patients also feel “slighted and shamed” by the guidelines, and are increasingly suicidal or turning to street drugs. We’ve also reported that the CDC has apparently done nothing to study the harms or even the possible benefits the guidelines have caused since they were released 18 months ago.

Instead of going back in time and selectively mining databases to fit preconceived notions about opioids, perhaps it is time for the CDC to take a giant step forward and see what its opioid guidelines have actually done.

Study Finds Heart Disease Biggest Risk from Opioids

By Pat Anson, Editor

People who take opioid medication for chronic pain are far more likely to die prematurely from cardiovascular and respiratory problems than they are from accidental overdoses, according to researchers at Vanderbilt University.

Their study, published in JAMA, suggests that many opioid related deaths have been misclassified as overdoses and that public health policy should be more focused on the risks of opioids causing cardiovascular problems.

Researchers looked at a database of nearly 23,000 Medicaid patients in Tennessee who were prescribed either opioids; anti-seizure nerve medications such as pregabalin (Lyrica) and gabapentin (Neurontin); or a low dose antidepressant for chronic non-cancer pain.  

After four months, there were 185 deaths in the opioid group, a mortality rate that that was 1.6 times greater than the patients taking anti-seizure drugs or antidepressants. More than two-thirds of the excess deaths were due to causes other than accidental overdose.

Over twice as many patients died from cardiovascular and respiratory problems (89) than from overdoses (34).

“The increased risk of cardiovascular death could be related to adverse respiratory effects of long-acting opioids. Opioids can cause or exacerbate sleep-disordered breathing, including both obstructive and central sleep apnea,” wrote lead author Wayne Ray, PhD, of the Vanderbilt University School of Medicine.

“More than two-thirds of the excess deaths for patients in the long-acting opioid group were not coded as being due to unintentional overdose. If there is this degree of misclassification, then previous research on opioid mortality, most of which has focused on overdose deaths identified from death certificates, has substantially underestimated the true risks of opioids.”

The Centers for Disease Control and Prevention uses death certificate codes in its reports on mortality. The agency estimates that nearly 19,000 Americans died from overdoses of prescription pain medication in 2014. However, CDC researchers admit some of the overdoses may have been counted twice, and that some overdoses from illicit opioids such as heroin and fentanyl may have been counted as prescription drug deaths.

One weakness of the Vanderbilt study is that it only looked at mortality rates in the first few months of treatment and did not include deaths from long-term medication use.

“The study finding that prescription of long acting opioids was associated with increased cardiovascular and other non-overdose mortality adds to the already considerable known harms of the opioids and thus should be considered when assessing the benefits and harms of medications for chronic pain,” Ray wrote. “Nevertheless, for some individual patients, the therapeutic benefits from long-acting opioid therapy may outweigh the modest increase in mortality risk.”

The mortality rate for chronic pain patients who died in a hospital was higher for patients given antidepressants and anti-seizure drugs than it was for opioids.

Are Opioids or Economics Killing White Americans?

By Pat Anson, Editor

Opinions are all over the map about a recent study by two Princeton University researchers, who estimate that nearly half a million white Americans died in the last 15 years due to a quiet epidemic of pain, suicide, alcohol abuse and opioid overdoses.

The husband and wife research team of Angus Deaton and Anne Case were careful not to point a finger at any one cause, but speculated that financial stress caused by unemployment and stagnant incomes may be behind the rising mortality of middle-aged whites. The deaths were concentrated in baby boomers with a high school education or less.

But some were quick to blame the “opioid epidemic.”

“An opioid overdose epidemic is at the heart of this rise in white middle-age mortality,” wrote psychiatrist Richard Friedman, MD, in an editorial that appeared in the New York Times under the headline “How Doctors Helped Drive the Addiction Crisis.”

“Driving this opioid epidemic, in large part, is a disturbing change in the attitude within the medical profession about the use of these drugs to treat pain,” said Friedman. “It is physicians who, in large part, unleashed the current opioid epidemic with their promiscuous use of these drugs; we have a large responsibility to end it.”

And what should doctors do to end the epidemic?

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Friedman said there was “strong evidence” that Motrin, Tylenol and other nonsteroidal anti-inflammatory drugs (NSAIDS) were “safer and more effective for many painful conditions than opioid painkillers.”

The Fresno Bee took a more nuanced view of what it called “the epidemic of pain and heartbreak.”

“If ever a set of numbers cried out for deeper examination, it is this one. Human frailty may be epidemic, but surely it is also no surprise that a generation raised with the expectation of a secure future might sink into depression, hostility, illness, anguish and rage when that future fails to transpire,” The Bee said in an editorial. “Whether the solution is better jobs, cheaper schools, more mental health care or less reliance on painkillers, the distress of America’s white working class has become a public health crisis.”

“White Americans who used to be able to support a family are now struggling even in dual income households, and there's a corresponding loss in stature and self-esteem. They are turning to prescription opioids in greater numbers than minorities,” said the Baltimore Sun. “The transition to a 21st (century) economy is literally killing some people, and the United States can ill afford to ignore this disturbing development.”

Overseas news outlets also tended to blame the rising death rate on a “ruthless economy.”

“These people are dying because history has unexpectedly thrown them on the scrapheap,” said The Guardian. “White baby boomers had high expectations of the future, yet many of them have lived to discover that they will be worse off than their parents.”

“(The) findings should awaken Americans to the price we pay for pursuing economic policies that enrich the few at the expense of the many,” said David Cay Johnston in a column for Al Jezeera America. “The harsh reality is that our economy is in many ways stuck in 1998 and that for poorly educated Americans, the economy has become a living nightmare with no expectation of a brighter tomorrow. The rise in drug and alcohol poisonings as well as the rising tide of suicides should not surprise. But these trends should disturb.”

What do you think? Is the economy to blame for the increasing number of deaths? Or is it opioids?

What’s Killing Middle-Aged White Americans?

By Pat Anson, Editor

A quiet epidemic of chronic pain, suicide, alcohol abuse and drug overdoses has killed a “lost generation” of nearly half a million middle aged white Americans in the last 15 years, according to a startling new study by Princeton University researchers.

Using data culled from a variety of sources and reports, researchers found a disturbing increase in the death rate for whites aged 45 to 54. Between 1999 and 2013, the mortality rate for middle aged whites rose by 2% annually, a reversal from previous decades when their death rate declined by an average of 1.8% a year.

The spike in mortality is estimated to have led to the early deaths of 488,500 white Americans, a figure comparable to the number of deaths caused by the AIDS epidemic.

 “This change reversed decades of progress in mortality and was unique to the United States; no other rich country saw a similar turnaround,” researchers Anne Case and Angus Deaton wrote in the study published in the Proceedings of the National Academy of Sciences. “This increase for whites was largely accounted for by increasing death rates from drug and alcohol poisonings, suicide, and chronic liver diseases and cirrhosis.”

No other race or ethnic group saw such an increase in mortality. African-Americans, Hispanics and those aged 65 and older continued to see their mortality rates fall.

The rising death rate for middle-aged whites was accompanied by declines in physical health, mental health and employment, as well as increases in chronic joint pain, neck pain, sciatica and disability.

It also coincided with a sharp increase in the prescribing of opioid pain medication, and seems likely to fuel a chicken and egg debate over which came first.

“The epidemic of pain which the opioids were designed to treat is real enough, although the data here cannot establish whether the increase in opioid use or the increase in pain came first. Both increased rapidly after the mid-1990s. Pain prevalence might have been even higher without the drugs, although long-term opioid use may exacerbate pain for some, and consensus on the effectiveness and risks of long-term opioid use has been hampered by lack of research evidence,” wrote Case and Deaton.

“Pain is also a risk factor for suicide. Increased alcohol abuse and suicides are likely symptoms of the same underlying epidemic, and have increased alongside it, both temporally and spatially.”

“The findings are astonishing, and a testament to the enormous toll opioids are taking in the U.S.,” said David Juurlink, MD, who heads the Division of Clinical Pharmacology and Toxicology at the University of Toronto. “It is very difficult to argue against cause-and-effect here. In my view it is a damning indictment of the widespread use of opioids for chronic pain, and should cause prescribers and patients alike to reflect on the role of these drugs, which have essentially no evidence behind them.”

Juurlink, who is a board member of Physicians for Responsible Opioid Prescribing (PROP), is advising the Centers Disease for Disease Control and Prevention (CDC) about its draft guidelines for the prescribing of opoids. He says it’s no coincidence that deaths in middle-aged whites rose just as opioid prescribing increased.

“It is an unarguable fact that opioids play a causal role in a good many of these deaths. People have drunk alcohol to excess for millenia, and have taken benzodiazepines needlessly for decades. And yet we see a striking surge in poisoning deaths coincident with surging opioid sales,” Juurlink wrote in an email to Pain News Network.

“As for suicide, you can put me on the record as speculating that opioids trigger suicide in some patients, and perhaps quite a high number. I raise this point because it's sometimes asserted that opioids can prevent suicide in patients with chronic pain. There is no evidence that this is true, but there are ample grounds to assert that they might in fact be a component cause.”

Another recent study published in JAMA found that drug overdose deaths associated with opioids nearly doubled in the last decade, rising from 4.5 deaths per 100,000 people in 2003 to 7.8 deaths per 100,000 in 2013.

But others says opioids are the not the cause of rising deaths, but more a symptom of a deeper problem.

“I can tell you absolutely that opioids do not lead this dysfunction.  Abuse, addiction, disability, and suicide are symptoms of a failing healthcare system,” says Terri Lewis, PhD, a rehabilitation specialist and patient advocate. “This population of white Americans has also been largely uninsured or underinsured.  They turn to self medication practices that involve alcohol because that is what is available.  Their acute care is often dependent on emergency room services where there is no continuity or recovery model in place.”

Deaths Hit Least Educated Hardest

The Princeton study found that death rates related to drugs, alcohol and suicides rose for middle-aged whites at all education levels, but the largest increases were seen among those with the least education. For those with a high school degree or less, deaths caused by drug and alcohol poisoning rose fourfold; suicides rose by 81 percent; and deaths caused by liver disease and cirrhosis rose by 50 percent.

“All cause” mortality rose by 22% for this least-educated group. Those with some college education saw little change in overall death rates, and those with a bachelor's degree or higher actually saw death rates decline.

The researchers speculated that financial stress may have played a role in the rising death rate. Median household incomes of whites began falling in the late 1990s, and wage stagnation hit especially hard those with a high school or less education.

“These were folks who were also disproportionately represented in the downturn of the economy and loss of jobs from rural communities,” says Lewis. “When the economy failed, their disability and reduced level of functioning did not allow them to migrate into other locations or jobs – their educational levels and physical limitations simply imposed too much of a barrier.  The loss of employment put many onto the disability roles.” 

The rise in mortality occurred in all regions of the U.S., although suicide rates were marginally higher in the South and West than in the Midwest and Northeast. In each region, death by way of accidental drug and alcohol poisoning rose at twice the rate of suicide.

In all age groups researchers said there were marked increases in deaths related to drug and alcohol poisoning, suicide and chronic liver disease and cirrhosis. The midlife group differed only in that the number of deaths was so large that it changed the direction of their overall mortality.

If that trend is not reversed, researchers warn, there will be an enormous cost to the healthcare system. 

“A serious concern is that those currently in midlife will age into Medicare in worse health than the currently elderly. This is not automatic; if the epidemic is brought under control, its survivors may have a healthy old age. However, addictions are hard to treat and pain is hard to control, so those currently in midlife may be a ‘lost generation’ whose future is less bright than those who preceded them,” they said.