Misdiagnosing Causes and Casualties in the Opioid War [Corrected]
Do the pain relief benefits of prescription opioids outweigh their addiction risks?
"The opioid crisis is an emergency," declared President Donald Trump in August. "And I am saying officially right now that it is an emergency, a national emergency. We are going to spend a lot of time, a lot of effort, and a lot of money on the opioid crisis."
As of this week, President Trump and his advisors have not yet completed the paperwork for an official national emergency declaration. So how much of a crisis is the "opioid epidemic"?
In 2015 some 33,000 Americans died from overdosing on various synthetic opioids. Some researchers forecast that as many as 500,000 Americans could die of opioid overdoses in the next decade. The drugs most associated with overdose deaths are prescription pain pills like oxycodone, along with black market heroin and fentanyl.
Lots of media reports have made pharmaceutical manufacturers, distributors, and "pill mill" physicians the chief villains in the rise of overdose deaths. "The Drug Industry's Triumph Over the DEA," published earlier this week by The Washington Post and CBS' 60 Minutes, is one such "exposé."
While it is true that some unscrupulous phyisicians and pharmacies have overprescribed opioid medications, Josh Bloom, director of Chemical and Pharmaceutical Sciences for the American Council of Science and Health provides a helpful guide to some of the deceptive claims being peddled by drug warriors. Specifically, Bloom decodes Andrew Kolodny's "The opioid epidemic in 6 charts," over at The Conversation.
Kolodny, executive director for Physicians for Responsible Opioid Prescribing, cites data from the National Institute on Drug Abuse showing that more 60,000 Americans died of drug overdoses in 2016. Bloom suggests that that assertion misleads readers into thinking that those deaths are mostly the result of taking prescription opioids.
The actual number of deaths associated with overdosing on prescription opioids was around 17,000 last year. And as Bloom points out, most of those overdose deaths occurred in conjunction with benzodiazepines (like Valium and Xanax) and black market heroin and fentanyl.
A recent Center for Disease Control Morbidity and Mortality Weekly Report focusing on drug overdose deaths in Ohio found that 90 percent of the decedents tested positive for fentanyl, 31 percent for cocaine, 27 percent for benzodiazepines, 23 percent for prescription opioids, and 6 percent for heroin. Once these are taken into account, Bloom estimates that "the number of deaths from opioid pills alone will be much lower, perhaps in the neighborhood of 5,000."
Bloom also objects to Kolodny's observation that the "effects of hydrocodone and oxycodone on the brain are indistinguishable from the effects produced by heroin." Both prescription opioids and heroin operate on the same receptors in the brain, but hydrocodone and oxycodone are four and two times less powerful, respectively, than heroin. And they are 200 and 100 times less powerful than fentanyl.
Long-term use of prescription "opioids are more likely to harm patients than help them because the risks of long-term use, such as addiction, outweigh potential benefit," Kolodny says. Bloom counters that the "absence of evidence is not evidence of absence." His main argument is that Kolodny cannot make his claim for the simple reason that no long term studies on the effects of opioids to manage chronic pain have been conducted.
In any case, Bloom cites 2010 research that the risk of addiction is below one percent for patients who use prescription opioids for short term pain control. A 2013 review similarly reports the risk of addiction is below one percent and concludes, "The available evidence suggests that opioid analgesics for chronic pain conditions are not associated with a major risk for developing dependence."
A 2015 review article in the Annals of Internal Medicine reported that "reliable conclusions about the effectiveness of long-term opioid therapy for chronic pain are not possible due to the paucity of research to date." However, the Annals reviewers were less sanguine than Bloom about prescribing opioids to treat pain. "Accumulating evidence supports the increased risk for serious harms associated with long-term opioid therapy, including overdose, opioid abuse, fractures, myocardial infarction, and markers of sexual dysfunction." The Annals review also notes that various studies found the prevalence of prescription opioid addiction ranging from 2 to 14 percent.
Some pharmaceutical companies, Bloom acknowledges, helped fuel the opioid problem by falsely claiming their medicines were less addictive and less subject to abuse than other pain medications. For example, Purdue Pharma, the manufacturer of Oxycontin, admitted it had misled physicians and paid in a fine of $653 million in 2007.
But given that most of the opioid deaths now result from consuming illicit drugs, Bloom argues Kolodny's effort to blame the problem on drug companies is now irrelevant.
Kolodny rejects the claim that the reformulation of prescription opioids after 2010 to make them more difficult to snort or inject pushed many users to black market heroin and even more dangerous substances in search of highs. Bloom points out that after 2010 the number of deaths attributed to prescription opioids flattened while those from heroin and fentanyl increased almost five-fold.
Bloom decries what he calls the "opioid pain refugee crisis," in which new federal rules restrict patient access to effective drugs to control severe pain. In 2012, the Institute of Medicine at the National Academy of Sciences issued a study, Relieving Pain in America, that reported: "Chronic pain affects about 100 million American adults—more than the total affected by heart disease, cancer, and diabetes combined. Pain also costs the nation up to $635 billion each year in medical treatment and lost productivity."
"We do not question that opioid misuse is a serious and growing public health problem," writes Arthur Lipman, editor of the Journal of Pain & Palliative Care Pharmacotherapy. "We do not, however, accept the simplistic solution of limiting opioid use that is advocated by many commentators as being rational. Although opioid overprescribing and access undoubtedly contribute to the problem, opioids are still seriously underprescribed for and unavailable to many legitimate patients with moderate to severe pain who need these medications to function adequately."
While Kolodny argues for substantially increasing restrictions on patient access to prescription opioids, he also urges federal and state governments to "ensure that millions of Americans now suffering from opioid addiction can access effective addiction treatment."
Instead of pursuing the failed Drug War policies of restriction and prohibition, one good way for President Trump to "spend a lot of money" to help those opioid users who do become addicted is to increase access to medication-assisted therapy programs as recently suggested by my Reason colleague Mike Riggs.
Disclosure: I have worked on a couple of projects for ACSH in the past, including my report, "Scrutinizing Industry-Funded Science: The Crusade Against Conflicts of Interest."
Correction:
Andrew Kolodny, executive director for Physicians for Responsible Opioid Prescribing, called to complain that my article was badly mistaken in some respects and had in others unfairly mischaracterized his views. He then led me through my article pointing to his specific concerns.
So from Kolodny's point of view, what did I get wrong? To the extent that the term drug warrior is associated with vigorous law enforcement of drug prohibition, I was clearly wrong to suggest that Kolodny is one. I also misconstrued Kolodny's claim that opioid users switched to heroin largely because it was "easier to obtain" as implying that he rejects the claim that oxycodone's reformulation in 2010 pushed opioid users toward black market heroin.
Below I provide more context and my responses to other objections raised by Kolodny.
Kolodny's first objection was to the way I summarized Josh Bloom's interpretation of Kolodny's opening statement: "Drug overdose deaths, once rare, are now the leading cause of accidental death in the U.S., surpassing peak annual deaths caused by motor vehicle accidents, guns and HIV infection." Bloom asserted that "most people will read what Kolodny wrote and arrive at the conclusion that 60,000 people were killed by prescription pain medications."
Is Bloom's interpretation unreasonable?
Kolodny follows up his opening claim by asserting: "The data show that the situation is dire and getting worse. Until opioids are prescribed more cautiously and until effective opioid addiction treatment becomes easier to access, overdose deaths will likely remain at record high levels."
In his next four paragraphs, Kolodny chiefly explains why he thinks that prescription opioids are responsible for engendering the opioid crisis and then observes: "Over the last two decades, as prescriptions for opioids began to soar, rates of addiction and overdose deaths increased in parallel."
His initial mention of heroin is to compare its effects with the prescription opioids hydrocodone and oxycodone. As evidence that Bloom's interpretation is wrong, Kolodny cited his observation: "Until 2011, most opioid overdose deaths involved prescription opioids. Then prescription opioid overdose deaths leveled off, while overdose deaths involving heroin began to soar."
Given Kolodny's frequent initial mentions and resolute focus on prescription opioids as being the chief cause of the opioid crisis, it seems likely that casual readers might well draw the inference that most overdose deaths are caused by them.
Next Kolodny objected to the way I summarized Bloom's response to Kolodny's claim that the "effects of hydrocodone and oxycodone on the brain are indistinguishable from the effects produced by heroin." Bloom actually writes, "Yes, they are." But Bloom then argues that simply noting the pharmacokinetic similarity between opioids is not enough. Bloom counters that "heroin packs a much more powerful punch than hydrocodone, especially at doses that are used by addicts." In an effort to clarify Bloom's point, I linked to some data comparing the relative strengths of various opioids.
In our phone conversation Kolodny properly countered that addicts can adjust the dosages of whatever opioids to which they have access to match the effects of any other opioid they have been using. I think he makes a good point and I regret any confusion that my interpretation may have caused readers.
We had a brief discussion about the research on the rates of addiction among users of prescribed opioids, and he noted that I had linked to research suggesting higher rates than those cited by Bloom. Kolodny made it clear that he thought the studies finding higher rates of addiction to prescription opioids more credible. We moved on.
Kolodny most vehemently objected to my assertion: "Kolodny rejects the claim that the reformulation of prescription opioids after 2010 to make them more difficult to snort or inject pushed many users to black market heroin and even more dangerous substances in search of highs." This was my attempt to summarize and interpret his claim: "A common misconception is that so-called "drug abusers" suddenly switched from prescription opioids to heroin due to a federal government "crackdown" on painkillers. There is a kernel of truth in this narrative. It's true that the vast majority of people who started using heroin after 1995 switched from prescription opioids because heroin was easier to obtain."
Kolodny also strongly insisted that there has been no "crackdown" on prescription opioids. Curiously, it is fairly easy to find several articles and sources that do report over many years that there has been a "crackdown." These range from USA Today (2013), PBS NewsHour (2015), The Daily Beast (2016), The Hill (2016), Alcoholism & Drug Abuse Weekly (2016), to The Chicago Tribune (2017).
Aspects of the "crackdown" described in these and other sources include the CDC's tightening opioid prescription guidelines (a move applauded by Kolodny), increasing DEA enforcement efforts against prescribing physicians, switching hydrocodone from the less regulated Schedule III to Schedule II, and reformulating oxycodone to make it harder to snort or inject.
As noted above, it is clear to me now that I misconstrued Kolodny's claim that opioid users switched to heroin largely because it was "easier to obtain" as implying that he rejects the claim that oxycodone's reformulation in 2010 pushed opioid users toward black market heroin. Nevertheless, the question is not solely about whether heroin was just easier to obtain, but easier to obtain compared to what? Specifically, lots of oxycodone users switched to heroin because they could no longer access forms of the prescription opioid they could easily snort or inject.
Lots of research, including a 2012 study to which I link in my article, finds that it was reformulation, not just the availability of cheaper heroin as suggested by Kolodny that was the primary reason that many painkiller addicts switched to heroin. "The most unexpected, and probably detrimental, effect of the abuse-deterrent formulation was that it contributed to a huge surge in the use of heroin, which is like OxyContin in that it also is inhaled or injected," explained the principal investigator of that study.
Another fascinating new (2017) National Bureau of Economic Research study, "How the Reformulation of OxyContin Ignited the Heroin Epidemic," reports: "Between 1999 and 2009, opioid death rates were rising rapidly but heroin death rates were much lower and increasing slowly. In 2010, this changed; over the next four years, heroin death rates increased by a factor of four while opioid death rates remained fairly flat." In fact, the researchers "date the changes precisely to the month following the reformulation of OxyContin."
Still, my summary suggestion that Kolodny rejects reformulation as a major factor in the rise of heroin overdose deaths is at least misleading; he doesn't discuss that possibility and instead focuses on comparative cheapness of the heroin alternative to prescribed opioid drugs. I think Bloom has the stronger argument when he notes, "Reasons for opioid abuse are multifactorial, but there is no question that epidemic began to escalate in 2010, not from any crackdown, but from an improvement in the formulation of abuse-resistant OxyContin and the unintended consequences that followed."
Kolodny further claimed that I had mischaracterized his views when I stated that he favors "substantially increasing restrictions on patient access to prescription opioids." He was concerned that readers would interpret that as suggesting that he favored more punitive DEA action against addicts. Given the fraught nature of the failed Drug War, it is entirely understandable that Kolodny is anxious that his views not be mistaken or misrepresented.
Still, as noted earlier, Kolodny does support the CDC's new more restrictive opioid prescribing guidelines. In addition, he favored moving hydrocodone from the DEA's Schedule III to Schedule II. He has also said that the DEA's recent deep cuts in the aggregate production quotas of prescription opioids are "too little, too late." And he praised the CVS pharmacy chain for announcing that it will limit most opioid prescriptions to seven days. I do agree that I should not have used the term "drug warrior" when characterizing Kolodny's policy endeavors. Nevertheless, it does not seem unreasonable to describe Kolodny as being in favor of "substantially increasing restrictions on patient access to prescription opioids."
I do try to get things right, but I occasionally do make mistakes. I do really appreciate Kolodny contacting me to let me know his concerns. I hope that this correction has made the discussion around the problems and policies associated with opioids, both licit and illicit, a bit clearer to readers.
