Tag: prescriptions

The Law of Unintended Consequences Strikes Again

Late last week UPI news ran a report by E.J. Mundell with the headline, “Government efforts to curb opioid prescriptions might have backfired.” It cites two separate studies published online in JAMA Surgery on August 22 that examined two different restrictive opioid policies that fell victim to the Law of Unintended Consequences.

The first study, by researchers at the University of Michigan, evaluated the impact of the Drug Enforcement Administration’s 2014 rescheduling of hydrocodone (Vicodin) from Schedule III to Schedule II. Prescriptions for Schedule III narcotics may be phoned or faxed in by providers, but Schedule II narcotics require the patient to see the prescriber in person in order to obtain a prescription. The DEA’s goal was to reduce the number of Vicodin pills, popular with non-medical users, available for diversion to the black market.

The study looked at 21,955 post-surgical patients across 75 hospitals in Michigan between 2012 and 2015 and found that the number of hydrocodone pills prescribed after the 2014 schedule change increased by an average of seven 5mg tablets. The total Oral Morphine Equivalent of prescribed hydrocodone did not change significantly after the DEA made hydrocodone Schedule II. However, the refill rate decreased after the change. The study’s abstract concluded, “Changing hydrocodone from schedule III to schedule II was associated with an increase in the amount of opioids filled in the initial prescription following surgery.”

As a practicing general surgeon, my initial reaction to this study was: “Tell me something I don’t know.” Prior to the 2014 schedule change, I would often start off prescribing a small amount of hydrocodone to some of my post-op patients (depending upon the procedure and the patient’s medical history) with the knowledge that I can phone in a refill for those patients who were still in need of it for their pain after the initial supply ran out. Once it was rescheduled, I changed my prescribing habits. Not wanting any of my patients to run out after hours, over a weekend, or on a holiday—when the office is closed and their only recourse would be to go to an emergency room or urgent care center to get a prescription refill—I increased the amount I prescribe (based on my best estimate of the maximum amount of days any individual patient might need hydrocodone) to reduce the chances of them needing a refill. This results in some patients having leftover Vicodin pills in their medicine cabinet. On the other hand, fewer of those patients need refills.

Not surprisingly, many of my clinical peers have done the same thing. It’s not a surprise because most physicians place the interests of their patients ahead of the interests of regulators and bureaucrats. So the adjustment made in postoperative hydrocodone prescribing was basically a “no brainer.” 

Prohibition Is the Obvious Cause of Opioid Crisis as CDC Releases Preliminary Casualty Numbers for 2017

Earlier this month the Centers for Disease Control and Prevention released preliminary estimates of the opioid overdose rate for 2017. The total overdose rate rose to approximately 72,000, up from a total overdose rate of 63,600 in 2016, an increase of roughly 10 percent. The total overdose rate includes deaths from numerous drugs in addition to opioids, such as cocaine, methamphetamine, and benzodiazepines. The opioid-related overdose rate increased as well, from a little over 42,000 in 2016 to over 49,000 in 2017. This increase occurred despite a 4 percent drop in heroin overdoses and a 2 percent drop in overdoses due to prescription opioids. A 37 percent increase in illicit fentanyl-related overdoses explains the jump in the death rate.

All of this is happening while the prescribing of high-dose opioids continues to decrease dramatically—over 41 percent between 2010 and 2015, with a recent report showing a further decrease of 16 percent during the year 2017.

This is more evidence, if any more was needed, that the opioid overdose problem is the result of non-medical users accessing drugs in the black market that results from drug prohibition. Whether these users’ drug of choice is OxyContin or heroin, the majority have obtained their drugs through the black market, not from a doctor. A 2007 study by Carise, et al in the American Journal of Psychiatry looked at over 27,000 OxyContin addicts entering rehab between the years 2001 and 2004 and found that 78 percent never obtained a prescription from a doctor but got the drugs through a friend, family member, or a dealer. 86 percent said they took the drug to “get high” or get a “buzz.” 78 percent also had a prior history of treatment for substance abuse disorder. And the National Survey on Drug Use and Health has repeatedly found roughly three-quarters of non-medical users get their drugs from dealers, family, or friends as opposed to a doctor.

Media and policymakers can’t disabuse themselves of the false narrative that the opioid problem is the product of doctors hooking their patients on opioids when they treat their pain, despite the large number of studies showing–and the Director of the National Institute on Drug Abuse stating—that opioids used in the medical setting have a very low addiction rate. Therefore, most opioid policy has focused on decreasing the number of pills prescribed. Reducing the number of pills also aims at making less available for “diversion” into the black market. This is making many patients suffer from undertreatment of their pain and causes some, in desperation, to turn to the black market or to suicide.

Since 2010, opioid policy has also promoted the development of abuse-deterrent formulations of opioids—opioids that cannot be crushed and snorted or dissolved and injected. As a just-released Cato Research Brief as well as my Policy Analysis from earlier this year have shown, rendering prescription opioids unsuitable for abuse has only served to make non-medical users migrate over to more dangerous heroin, which is increasingly laced with illicit fentanyl. 

This is how things always work with prohibition. Fighting a war on drugs is like playing a game of “Whac-a-mole.” The war is never-ending and the deaths keep mounting.

The so-called “opioid crisis” has morphed into a “fentanyl and heroin crisis.” But it has been an unintended consequence of prohibition from the get go.

There Is More Than One Way to “Spin” a Stat

I recently wrote about how ideology and confirmation bias has infiltrated research into the opioid overdose issue. I spoke about how researchers can “spin” their findings to comport with the prevailing narrative and improve the likelihood of getting published in peer-reviewed journals.

An example occurred yesterday, when the University of Michigan’s Institute for Healthcare Policy and Innovation announced, with the headline “Unwise opioids for wisdom teeth: Study shows link to long-term use in teens and young adults,” the publication of a research letter in JAMA that day by a team of its researchers.

The study of over 70,000 dental patients, ranging from 13 to 30 years in age, who had wisdom teeth extracted between 2009 and 2015 found, 

In all, 1.3 percent of 56,686 wisdom tooth patients who filled their opioid prescription between 2009 and 2015 went on to persistent opioid use, defined as two or more prescriptions filled in the next year written by any provider for any reason. That’s compared with 0.5 percent of the 14,256 wisdom tooth patients who didn’t fill a prescription.” 

Set aside the fact this study shows prolonged use is very low. Is there something inherently bad about refilling opioid prescriptions and staying on opioids longer than the average person if one is not addicted? Since we know that opioids have very few harmful effects on organs compared to alcohol, acetaminophen, or NSAIDs (with prolonged use), and since the addiction and misuse rate is somewhere around 1 percent, why are the authors so upset if some people stay on the drug longer than others. The lead author calls this a “long term ill effect.” Really?

Meanwhile, on the same day, another research letter was also published in JAMA by researchers at Brigham and Women’s Hospital in Boston that looked at 1.3 million patients who received 22 types of surgical procedures between the years 2004 and 2015. The study found a 30-day post-discharge overdose rate of 10.3 per 100,000 patients (0.01 percent), dropping to 3.2 overdoses per 100,000 patients (0.0032 percent) for those 61 to 90 days post-discharge. The authors found overdoses within 30 days post-discharge were very low in patients who were “opioid naïve”—2.8 per 100,000 patients (0.0028 percent)—as opposed to patients who were receiving opioids prior to surgery. In patients who were chronically receiving high-dose opioids prior to the operation (defined by the authors as greater than the equivalent of 100mg of morphine per day) that rate jumped to 142.5 per 100,000 patients (0.14 percent).

The authors stated in their concluding discussion:

This study demonstrated that opioid overdose after surgical discharge was rare. Patients were at risk of experiencing an overdose after leaving the hospital, especially in the first month. Furthermore, patients using high quantities of opioids preoperatively were at a heightened risk compared with those not receiving high-dose opioid therapy prior to the operation.”

The big takeaway from this study is that overdose rates in patients discharged on opioids postoperatively are extremely low—even in those who had been chronically receiving high-dose opioids preoperatively. But the authors of the study spent most of the time discussing the fact that overdoses can and do occur in patients discharged from surgery on opioids and occur more frequently in patients who had been on opioids preoperatively.

Give credit to the medical news service MedPage Today for providing dispassionate, no-spin coverage to both studies by covering them together in a story on August 7 entitled: “Post-Surgery Overdoses Are Rare—but higher odds of persistent use seen following some procedures.”

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Politics, Confirmation Bias, and Opioids

This post co-authored with Rafael Fonseca, MD, Chairman of the Department of Medicine, Mayo Clinic, Phoenix, AZ

Much has been written about how politics and ideology influence research funding, suppress research in certain areas, and lead to the cherry-picking and misrepresentation of evidence in support of a narrative or agenda. Science journalist John Tierney explored “The Real War on Science” in an excellent essay in City Journal in 2016. Reflecting on this phenomenon in 2011, Patrick J. Michaels stated:

The process is synergistic and self-fulfilling. Periodicals like Science are what academia uses to define the current truth. But the monolithic leftward inclination of the reviewing   community clearly permits one interpretation (even if not supported by the results) and not another. This type of blatant politicized science is becoming the norm in the environmental arena, and probably has infiltrated most every other discipline, too.

It certainly has infiltrated research into the emotionally charged opioid overdose problem afflicting the US and many other western nations. Policy decisions have been rooted in a narrative seemingly immune to the facts: that the problem is largely the result of greedy pharmaceutical companies manipulating careless and poorly-trained doctors into “hooking” patients on highly addictive opioids and condemning them to a nightmarish life of drug addiction.

Tierney writes of confirmation bias—the tendency of people to seek out and accept information that confirms their beliefs and prejudices. He bemoans the “groupthink” that allows confirmation bias to infiltrate the peer review process. He cites a well-known study that demonstrated reviewers were more likely to find problems with a study’s methodology if the findings were contrary to their prejudices yet overlook methodological shortcomings if the findings were confirmatory.

Sometimes investigators try to “spin” their findings to make them comport to the narrative and appear confirmatory, increasing the likelihood that their research gets published. 

Both of us are practicing physicians, and each of us recently experienced reminders that research into the opioid overdose issue is not exempt from politicization and confirmation bias. We would like to present two recent examples where this confirmation bias became self-evident. 

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Why Is the OECD Trying to Connect Labor Market Conditions and Opioids?

story in today’s Wall Street Journal discusses the latest report from the Organization for Economic Cooperation and Development on ”prime age” (25-54) labor-force participation rates among its 35 member countries through the last quarter of 2017. While the US rate has improved, it remains below the average OECD rate, lagging behind such developed countries as Japan and the UK. What’s puzzling is why the authors of the report decided to weigh in on the opioid overdose issue.

Noting that per capita opioid prescriptions in the US are “significantly higher” than in other OECD countries, the report finds that participation rates for all adults (not limited to prime age) vary from state to state. The rate was lowest in West Virginia at 53 percent, and highest in North Dakota at 71 percent. It mentioned that opioid prescription rates are “generally higher” in those states with lower labor participation rates, leading it to declare that the use of opioid drugs “appears to be connected” to labor market conditions.

The number of opioid prescriptions has been dropping steadily in the US since it peaked in 2010. In fact, high-dose opioid prescriptions are down over 41 percent. An April 2018 report from the American Medical Association trumpeted a 22 percent decrease in opioid prescriptions between 2013 and 2017. 

The false narrative dominating the media and driving opioid policy blames opioid abuse and overdoses on doctors addicting their patients to pain pills. The near quadrupling of the sales of prescription opioids between 1999 and 2014 is often used to help make the case. 

Yet correlation does not imply causation. The AMA made note of this in its April report on the dramatic drop in prescriptions when it stated:

It is notable that every state has experienced a decrease, but this is tempered by the fact that deaths related to heroin and illicit fentanyl are increasing at a staggering rate, and deaths related to prescription opioids also continue to rise. These statistics again prove that simply decreasing prescription opioid supplies will not end the epidemic.

Data from the Centers for Disease Control and Prevention show that overdoses—especially from fentanyl and heroin—continue to soar as prescription rates decline on the state level as well. 

The principle that correlation does not imply causation also applies to the observations in the OECD report.

The OECD report mentions that the overall labor-force participation rate tends to be lower in states where disability rates are higher. And West Virginia is a leader among states with respect to the percentage of its population on Social Security Disability benefits at 3.9 percent. It therefore points to a “possible connection between drug use and disability,” adding “addiction ultimately impairs participation.” It is certainly reasonable to expect that patients disabled by chronic severe pain conditions will be prescribed opioids. But there is no evidence that opioid use increases disability rates. In fact, Cochrane systematic studies in 2010 and 2012 found an addiction rate of approximately 1 percent in chronic non-cancer pain patients on long-term opioids. And many chronic pain patients are gainfully employed but have to stop working when they are cut-off from their opioids and their pain becomes debilitating. 

As I have written here and here, the overdose crisis was never about doctors and patients. It has always been primarily the result of non-medical users accessing drugs in the dangerous black market that results from drug prohibition.

Because correlation does not imply causation the OECD report carefully avoids drawing conclusions by using phrases like “appears to be connected” and “generally higher.” But its allusion to a connection between opioid prescribing and the labor participation rate is intellectually irresponsible and seems a gratuitous attempt to patronize the opioid policy establishment.

While Politicians Cut Opioid Prescriptions, Fentanyl—With Help From the “Dark Web” and the USPS— Becomes the Number One Killer

A May 22 story in Bloomberg News describes with painstaking detail the underground pipeline through which the powerful synthetic opioid fentanyl floods the US market. According to the Drug Enforcement Administration, while the Mexican cartel plays a role by using its well-established heroin and methamphetamine distribution networks, most of the fentanyl comes in to the US from China. 

The raw materials to make the synthetic opioids are cheap and they can be manufactured rather quickly in small laboratories. The laboratories are constantly creating new variations so as to skirt restrictions the Chinese government places on existing fentanyl analogs. Online distributors throughout China sell these products, making their transactions over the “dark web,” often paid with cryptocurrency, and frequently ship the products to the US via the US Postal Service or United Parcel Service. 

Many dealers purchase and use pill presses to make counterfeit OxyContin or Vicodin pills and trick non-medical users into thinking they are buying the real thing. That’s how Prince died. He preferred to abuse Vicodin (hydrocodone). Records show he never got prescriptions from doctors. He died from ingesting counterfeit Vicodin pills he obtained on the black market that turned out to be fentanyl.

The DEA reports this is the way most fentanyl makes its way to the street. As we doctors know, most pharmaceutical-grade fentanyl made for medical use does not get diverted on to the streets. In fact, the forms usually prescribed to outpatients—skin patches, lozenges, buccal films—are not very suitable for non-medical use.

The Centers for Disease Control and Prevention reports that fentanyl was responsible for 26,000 overdose deaths in 2017. But already in 2016 fentanyl accounted for more than 20,000 of the roughly 64,000 total overdose deaths (which include cocaine, methamphetamine, and benzodiazepines). Heroin came in second with more than 15,000. In fact, for a few years now, fentanyl and heroin have accounted for the majority of overdose deaths. And a great majority of those deaths had multiple other drugs on board. In New York City in 2016, three-quarters of overdose deaths were from fentanyl and heroin, and 97 percent of overdoses had multiple other drugs on board—46 percent of the time it was cocaine.

Fentanyl overdoses in the US have been rising at a rate of 88 percent per year since 2013. Heroin overdoses have been increasing at a rate of 19 percent per year since 2014 after climbing 33 percent per year from 2010-2014. Meanwhile, overdose deaths from prescription-type opioids have been increasing at a stable rate of 3 percent per year since 2009.

The National Survey on Drug Use and Health reports non-medical use of prescription opioids peaked in 2012, and total prescription opioid use in 2014 was lower than in 2012. And the survey repeatedly reports less than 25 percent of non-medical users see a doctor in order to get a prescription. Three-quarters obtain their drugs through a friend or family member or a drug dealer.

Meanwhile, while all this is going on, policymakers in Washington and in state capitals seem intent on getting the opioid prescription rate down further. State-based prescription drug monitoring programs have succeeded in reducing the prescription of high-dose opioids by over 41 percent since 2010, the peak year of opioid prescribing. And opioid production quotas, set by the DEA, were reduced 25 percent last year and another 20 percent this year, generating acute shortages of injectables in hospitals across the nation that is harming patients.

With all the evidence that the majority of non-medical users are not patients—with all the evidence that prescription rates have come down while overdose rates keep going up—with all the evidence of fentanyl and heroin flooding the black market and causing those deaths, it is time for policymakers to disabuse themselves of the false narrative to which they’ve been stubbornly clinging. This narrative blames the overdose problem on doctors prescribing pain relievers to their patients. The overdose problem has always been primarily caused by non-medical users accessing drugs in the dangerous black market created by drug prohibition. And our current restrictive policy is only driving up the death rate by pushing these users to more dangerous drugs while making patients suffer in the process.

What’s the definition of insanity?

New Research Reinforces Earlier Studies Suggesting PDMPs Are Adding to Opioid Overdose Rate

study published last year by researchers at the University of Pennsylvania and Pennsylvania State University found that state Prescription Drug Monitoring Programs (PDMPs), a popular method used to drive down the opioid prescription rate, do not drive down opioid overdose death rates, but might have the unintended consequence of adding to them, by driving users to the underground market where dangerous drugs like fentanyl and heroin await them. Another study last October by a Purdue University researcher found that while PDMPs drove down the prescription rate of oxycodone, they significantly drove up the rate of heroin use.

Yesterday the Annals of Internal Medicine published a systematic research review by Columbia University epidemiologist David Fink and others that drew the same conclusion. The authors stated, “Evidence that PDMP implementation either increases or decreases nonfatal or fatal overdoses is largely insufficient, as is evidence regarding positive associations between specific administrative features and successful programs.” They added, “implementation of PDMPs may have unintended negative outcomes—namely, increased rates of heroin-related overdose.”

Meanwhile, all 50 states have implemented PDMPs and state and federal policymakers seem focused on beefing them up. This is driven by the mistaken belief that the opioid overdose rate is primarily the result of doctors over-prescribing opioids to patients. As I have written numerous times, the overdose crisis is primarily a product of drug prohibition, as non-medical users access drugs in the dangerous black market. PDMPs might be responsible for the dramatic drop in the opioid prescription rate these last 8 years (the rate peaked in 2010), but as the prescription rate has dropped the overdose rate has increased—while fentanyl and heroin are now causing these overdoses the majority of the time.

How much more evidence will it take before policymakers finally realize their approach is not evidence-based but is contributing significantly to the overdose crisis?