Tag: Opioids

Add Hepatitis C to the List of Unintended Consequences of Abuse-Deterrent Opioids

One year ago Cato published my policy analysis, “Abuse-Deterrent Opioids and the Law of Unintended Consequences,” which provided strong evidence that reformulating opioids, so that they could not be crushed for snorting or dissolved for injecting by nonmedical users, only served to drive nonmedical users to more dangerous, readily available, and cheaper heroin provided by the efficient black market. 

The evidence included a RAND study that found “a substantial share of the dramatic increase in heroin deaths since 2010 can be attributed to the reformulation of OxyContin” which replaced regular OxyContin in 2010. It also included a study from researchers at Notre Dame and Boston Universities that found:

When we combine heroin and opioid deaths together, we find no evidence that total heroin and opioid deaths fell at all after the reformulation—there appears to have been one-for-one substitution of heroin deaths for opioid deaths.

Now comes a new RAND study that finds the abuse-deterrent reformulation of OxyContin led to an increase in cases of hepatitis C from IV drug use. As nonmedical users switched from OxyContin to injectable heroin, more became exposed to hepatitis C, transmitted by needle sharing.

The study compared states with above-median misuse rates of OxyContin to states with below-median misuse rates before and after the drug’s reformulation—from 2004 to 2015. Prior to the reformulation there was almost no difference in hepatitis C infection rates between the states. After the reformulation, states with above-median misuse rates saw a 222 percent increase in hepatitis C infections, while the below-median states saw a 75 percent increase during the same period. 

Add hepatitis C to the list of unintended consequences from abuse-deterrent reformulation of opioids.

Despite mounting evidence that abuse-deterrent reformulation of opioids has done nothing to reduce overdoses but may in fact be adding to them, the Food and Drug Administration continues to encourage pharmaceutical manufacturers to bring more abuse-deterrent formulations to market. As was the case with OxyContin, reformulation often results in extension of existing patents, reducing competition from generics and allowing patent holders to charge and profit more from their product. So opioid manufacturers are answering the FDA’s call for more abuse-deterrent reformulations.

Now that we have strong evidence that abuse-deterrent formulations spread disease as well as death, perhaps the FDA will reconsider this ill-advised policy.

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The FDA Bends Over Backwards To Get Drug Makers To Ask Them To Make Naloxone OTC

Press reports have created the impression that the opioid overdose antidote naloxone is now available over the counter. But in fact, the drug is still classified in the US as prescription only, so states have developed workarounds to make it easier for patients to obtain it without going to a doctor for a prescription. In most states, patients can get naloxone by going up to the counter and asking the pharmacist, who is legally authorized by the state to dispense it. 

But some states prohibit third parties from obtaining a prescription for another person, so people in those states who wish to have the antidote available because they have a friend or relative who uses opioids cannot obtain it. And experience shows that many pharmacists choose to not stock naloxone or participate in any distribution program. Furthermore, the stigma now attached to opioid use has deterred many patients from going up to the pharmacy counter and explaining to a pharmacist why they need naloxone.

To get around such obstacles, Australia and Italy have designated naloxone as a truly over-the-counter drug. People can discreetly buy it off the shelf and check out at the cash register.

The Food and Drug Administration is on record since at least 2016 as believing that it is probably appropriate for naloxone to be rescheduled as OTC and has encouraged manufacturers to petition the FDA to that end. Yesterday  FDA Commissioner Gottlieb announced the FDA has even gone to the trouble of designing Drug Facts Labels (DFL) required of manufactures for their products to be sold over the counter, and has even tested these labels for “consumer comprehension” in front of focus groups. The Commissioner stated in the announcement that this represents an unprecedented effort to facilitate and speed up the reclassification of naloxone from prescription-only to OTC.

This is commendable. But as I have written herehere, and here, the Commissioner does not have to wait for manufacturers, who may lack the incentive, to request the move to OTC. Under FDA regulations, the FDA can undertake reclassification review at the request of “any interested person,” or the Commissioner himself. States may petition the FDA for reclassification. Finally, if all else fails, Congress can order the reclassification.

The FDA should no longer wait for manufacturers to ask them to make this lifesaving drug more accessible to those in need.

Today’s Drug Abusers Did Not Derive From Yesterday’s Patients

We learned last week that the 2017 drug overdose numbers reported by the US Centers for Disease Control and Prevention clearly show most opioid-related deaths are due to illicit fentanyl and heroin, while deaths due to prescription opioids have stabilized, continuing a steady trend for the past several years. I’ve encouraged using the term “Fentanyl Crisis” rather than “Opioid Crisis” to describe the situation, because it more accurately points to its cause—nonmedical users accessing drugs in the dangerous black market fueled by drug prohibition—hoping this will redirect attention and lead to reforms that are more likely to succeed. But the media and policymakers remain unshakably committed to the idea that the overdose crisis is the product of greedy pharmaceutical companies manipulating gullible and poorly-trained doctors into over-prescribing opioids for patients in pain and ensnaring them in the nightmare of addiction.

As a result, most of the focus has been on pressing health care practitioners to decrease their prescribing, imposing guidelines and ceilings on daily dosages that may be prescribed, and creating surveillance boards to enforce these parameters. These guidelines are not evidence-based, as Food and Drug Administration Commissioner Scott Gottlieb seems to realize, and have led to the abrupt tapering of chronic pain patients off of their medication, making many suffer desperately. An open letter by distinguished pain management experts appeared last week in the journal Pain Medicine criticizing current policies for lacking a basis in scientific evidence and generating a “large-scale humanitarian issue.” 

Current policy has brought high-dose prescriptions down 41 percent between 2010 and 2016, another 16.1 percent in 2017, and another 12 percent this year. Yet overdose deaths continue to mount year after year, up another 9.6 percent in 2017.

One might expect the obvious prevalence of heroin and illicit fentanyl among overdose deaths would make policymakers reconsider the relationship between opioid prescribing, nonmedical use, and overdose deaths. The data certainly support viewing the overdose crisis as an unintended consequence of drug prohibition: nonmedical users preferred to use diverted prescription opioids and, as supplies became tougher to come by in recent years, the efficient black market responded by filling the void with cheaper and more dangerous heroin and fentanyl.

No Let Up On The Bad News About Overdose Deaths

The National Center for Health Statistics (NCHS) just issued Data Brief Number 329, entitled “Drug Overdose Deaths in the United States, 1999-2017.” Drug overdose deaths reached a new record high, exceeding 70,000 deaths in 2017, a 9.6 percent increase over 2016. That figure includes all drug overdoses, including those due to cocaine, methamphetamines, and benzodiazepines. The actual breakdown according to drug category will be reported in mid-December. However, estimates are opioid-related deaths will account for roughly 49,000 of the total overdose deaths. 

The big takeaways, quoting the report:

- The rate of drug overdose deaths involving synthetic opioids other than methadone, which include drugs such as fentanyl, fentanyl analogs, and tramadol, increased from 0.3 per 100,000 in 1999 to 1.0 in 2013, 1.8 in 2014, 3.1 in 2015, 6.2 in 2016, and 9.0 in 2017.The rate increased on average by 8% per year from 1999 through 2013 and by 71% per year from 2013 through 2017.

-The rate of drug overdose deaths involving heroin increased from 0.7 in 1999 to 1.0 in 2008 to 4.9 in 2016. The rate in 2017 was the same as in 2016 (4.9).

-The rate of drug overdose deaths involving natural and semisynthetic opioids, which include drugs such as oxycodone and hydrocodone, increased from 1.0 in 1999 to 4.4 in 2016. The rate in 2017 was the same as in 2016 (4.4).

-The rate of drug overdose deaths involving methadone increased from 0.3 in 1999 to 1.8 in 2006, then declined to 1.0 in 2016. The rate in 2017 was the same as in 2016 (1.0).

Despite the fact that overdose deaths from prescription opioids—and even heroin—have stabilized, the overdose rate continues to climb due to the surge in fentanyl deaths. 

This has happened despite policies in place aimed at curtailing doctors from prescribing opioids to their patients in pain. Prescription surveillance boards and government-mandated prescribing limits have pushed prescribing down dramatically. High-dose prescriptions were down 41 percent between 2010 and 2016, another 16.1 percent in 2017, and another 12 percent this year.

Policies aimed at curbing prescribing are based on the false narrative that the overdose crisis is primarily the result of greedy drug makers manipulating gullible doctors into overtreating patients in pain and hooking them on drugs. But as I have written in the past, , the overdose crisis has always been primarily the result of non-medical users accessing drugs in the dangerous black market that results from prohibition. As the supply of prescription opioids diverted to the underground gets harder to come by, the efficient black market fills the void with other, more dangerous drugs. Lately, the synthetic opioid fentanyl has emerged as the number one killer.

In a New York Times report on the matter today, Josh Katz and Margot Sanger-Katz hint that policymakers are aiming at the wrong target by stating, “Recent federal public policy responses to the opioid epidemic have focused on opioid prescriptions. But several public health researchers say that the rise of fentanyls requires different tools. Opioid prescriptions have been falling, even as the death rates from overdoses are rising.”

Prescription opioids are not the cause of the overdose death crisis. Neither is fentanyl, despite the fact that it is now the primary driver of the rising death rate. The ultimate cause of the drug overdose crisis is prohibition. US policymakers should drop the false narrative and face reality, like Portuguese health authorities did 17 years ago.

Portugal, in 2001, recognized that prohibition was driving the death rate. At the time it had the highest overdose rate in Western Europe. It decriminalized all drugs and redirected efforts towards treatment and harm reduction. Portugal saw its population of heroin addicts drop 75 percent, and now has the lowest overdose rate in Europe. It has been so successful that Norway is about to take the same route.

At a minimum, policymakers in the U.S. should turn to harm reduction. They should expand syringe exchange and supervised injection facilities, lighten the regulatory burden on health care practitioners wishing to treat addicts with medication-assisted treatments such as methadoneand buprenorphine, and reschedule the overdose antidote naloxone to a truly over-the-counter drug.

Unless this happens, we should expect more discouraging news from the NCHS in the years ahead.

 

Better Late Than Never?

As I have written many times before, the opioid prescribing guidelines put forth by the Centers for Disease Control and prevention have been criticized for not being evidence-based. This has even caused the Food and Drug Administration to begin the process of developing its own set of guidelines.

In publishing the guidelines, the CDC emphasized they were meant to be suggestive, not “prescriptive,” pointing out that health care practitioners know their patients’ situations better than any regulators and should therefore individualize their prescribing to meet their patients’ unique needs. 

That has not prevented the majority of states from implementing opioid prescribing guidelines that place limits on the dose, amount, and length of time that doctors can prescribe opioids—usually restricting the dose of opioids to a maximum of 90 MME (morphine milligram equivalents) per day. According to the National Conference of State Legislatures at least 30 states have implemented such guidelines. These guidelines have caused many health care practitioners to return to the undertreatment of pain for which they were criticized in the 1980s and 90s. And it has driven many chronic pain patients to desperation as their doctors abruptly taper their pain medication or cut them off entirely.

The American Medical Association has gently criticized the misinterpretation and misapplication of the CDC guidelines in the past. Now two and a half years after the CDC published its guidelines, the AMA has taken a more adamant stand. This week, at the AMA’s interim meeting in Maryland, its House of Delegates resolved:

RESOLVED that our AMA affirms that some patients with acute or chronic pain can benefit from taking opioids at greater dosages than recommended by the CDC Guidelines for Prescribing Opioids for chronic pain and that such care may be medically necessary and appropriate. 

RESOLVED that our AMA advocate against the misapplication of the CDC Guidelines for Prescribing Opioids by pharmacists, health insurers, pharmacy benefit managers, legislatures, and governmental and private regulatory bodies in ways that prevent or limit access to opioid analgesia.

RESOLVED that our AMA advocate that no entity should use MME thresholds as anything more than guidance, and physicians should not be subject to professional discipline, loss of board certification, loss of clinical privileges, criminal prosecution, civil liability, or other penalties or practice limitations solely for prescribing opioids at a quantitative level above the MME thresholds found in the CDC Guidelines for Prescribing Opioids.

Sadly, the opiophobia-driven policy train left the station long ago. As an eternal optimist, my initial reaction is to think, “better late than never,” and to hope this new resolution will cause policymakers to reconsider their misguided policy. But the cynical voice inside me responds with a more negative cliché: “a day late and a dollar short.”

 

 

 

As If We Needed It, More Evidence Emerges Showing That The Government Has Changed The Opioid Crisis Into a Fentanyl Crisis

Speaking last week at a National Opioid Summit in Washington, DC, Attorney General Jeff Sessions reported opioid prescriptions fell another 12 percent during the first eight months of 2018, saying ‘We now have the lowest opioid prescription rates in 18 years.” Some of this was no doubt the result of the chilling effect that prescription surveillance boards have had on the prescribing patterns of physicians. For example, Sessions announced the Trump administration has charged 226 doctors and 221 medical personnel with “opioid-related crimes,” and this has not gone unnoticed by health care practitioners.

Sessions also pledged to meet the goal of a 44 percent overall reduction in the production of opioids permitted by the Drug Enforcement Administration. The DEA, which sets quotas on the production of opioids by US manufacturers, began the process with a 25 percent reduction in 2016 and another 20 percent reduction in 2017. This has led to shortages of injectable opioids in many hospitals, affecting the delivery and quality of care.

Meanwhile, the DEA reported in a Joint Intelligence Report that overdoses in Pennsylvania continued to rise, with 5,456 fatal overdoses in 2017, a 65 percent increase over 2015. Only 20 percent of those overdoses involved prescription opioids, with most deaths involving multiple drugs in combination—usually fentanyl, heroin and cocaine, as well as counterfeit prescription opioids (usually made of illicit fentanyl and heroin pressed into pills). The report stated heroin and fentanyl were found in 97 percent of Pennsylvania’s counties.

Prescription opioids were also responsible for just 20 percent of the fatal overdoses in Massachusetts in 2015, where researchers at Boston University reported last week in the American Journal of Public Health that Opioid Use Disorder among people over age 11 grew to 4.6 percent of the population that year. 

The Massachusetts Department of Public Health reports a modest tapering in the fatal overdose rate, from 2,154 in 2016 to 2,069 in 2017, and estimates up to 1,053 have occurred in the first 6 months of 2018. During the first quarter of 2018, 90 percent of those deaths involved fentanyl, 43 percent involved cocaine, 34 percent involved heroin, and 20 percent involved prescription opioids. Fentanyl is responsible for sustaining the death rate in Massachusetts at near-record levels.

What jumps out of these numbers is the fact that efforts to get doctors to curtail their treatment of pain have not meaningfully reduced the overdose rate. They have just caused non-medical users of opioids to migrate over to more dangerous heroin and fentanyl. Fentanyl and heroin—not prescription opioids—are now the principal drugs behind the gruesome mortality statistics. 

Addressing the overdose crisis by focusing on doctors treating patients aims at the wrong target. And patients are suffering—often desperately— in the process. The cause has been drug prohibition from the get-go. If policymakers can’t muster the courage to admit and address that fact, then they should at least put the lion’s share of reform efforts into mitigating the harmful unintended consequences of prohibition. I wrote about this here.

Addiction Abuse

Hardly a day goes by without a report in the press about some new addiction. There are warnings about addiction to coffee. Popular psychology publications talk of “extreme sports addiction.” Some news reports even alert us to the perils of chocolate addiction. One gets the impression that life is awash in threats of addiction. People tend to equate the word “addiction” with “abuse.” Ironically, “addiction” is a subject of abuse.

The American Society of Addiction Medicine defines addiction as a “chronic disease of brain reward, motivation, memory and related circuitry…characterized by the inability to consistently abstain, impairment in behavioral control, craving” that continues despite resulting destruction of relationships, economic conditions, and health. A major feature is compulsiveness. Addiction has a biopsychosocial basis with a genetic predisposition and involves neurotransmitters and interactions within reward centers of the brain. This compusliveness is why alcoholics or other drug addicts will return to their substance of abuse even after they have been “detoxed” and despite the fact that they know it will further damage their lives. 

Addiction is not the same as dependence. Yet politicians and many in the media use the two words interchangeably. Physical dependence represents an adaptation to the drug such that abrupt cessation or tapering off too rapidly can precipitate a withdrawal syndrome, which in some cases can be life-threatening. Physical dependence is seen with many categories of drugs besides drugs commonly abused. It is seen for example with many antidepressants, such as fluoxetine (Prozac) and sertraline (Zoloft), and with beta blockers like atenolol and propranolol, used to treat a variety of conditions including hypertension and migraines. Once a patient is properly tapered off of the drug on which they have become physically dependent, they do not feel a craving or compulsion to return to the drug.

Some also confuse tolerance with addiction. Similar to dependency, tolerance is another example of physical adaptation. Tolerance refers to the decrease in one or more effects a drug has on a person after repeated exposure, requiring increases in the dose.

Science journalist Maia Szalavitz, writing in the Columbia Journalism Review, ably details how journalists perpetuate this lack of understanding and fuel misguided opioid policies.

Many in the media share responsibility for the mistaken belief that prescription opioids rapidly and readily addict patients—despite the fact that Drs. Nora Volkow and Thomas McLellan of the National Institute on Drug Abuse point out addiction is very uncommon, “even among those with preexisting vulnerabilities.” Cochrane systematic studies in 2010 and 2012 of chronic pain patients found addiction rates in the 1 percent range, and a report on over 568,000 patients in the Aetna database who were prescribed opioids for acute postoperative pain between 2008 and 2016 found a total “misuse” rate of 0.6 percent. 

Equating dependency with addiction caused lawmakers to impose opioid prescription limits that are not evidence-based, and is making patients suffer needlessly after being tapered too abruptly or cut off entirely from their pain medicine. Many, in desperation, seek relief in the black market where they get exposed to heroin and fentanyl. Some resort to suicide. There have been enough reports of suicides that the US Senate is poised to vote on opioid legislation that “would require HHS and the Department of Justice to conduct a study on the effect that federal and state opioid prescribing limits have had on patients — and specifically whether such limits are associated with higher suicide rate.” And complaints about the lack of evidence behind present prescribing policy led Food and Drug Administration Commissioner Scott Gottlieb to announce plans last month for the FDA to develop its own set of evidence-based guidelines.

Now there is talk in media and political circles about the threats of “social media addiction.” But there is not enough evidence to conclude that spending extreme amounts of time on the internet and with social media is an addictive disorder. One of the leading researchers on the subject stresses that most reports on the phenomenon are anecdotal and peer-reviewed scientific research is scarce. A recent Pew study found the majority of social media users would not find it difficult to give it up. The American Psychiatric Association does not consider social media addiction or “internet addiction” a disorder and does not include it in its Diagnostic and Statistical Manual of Mental Disorders (DSM), considering it an area that requires further research.

This doesn’t stop pundits from warning us about the dangers of social media addiction. Some warnings might be politically motivated. Recent reports suggest Congress might soon get into the act. If that happens, it can threaten freedom of speech and freedom of the press. It can also generate biliions of dollars in government spending on social media addiction treatment.

Before people see more of their rights infringed or are otherwise harmed by unintended consequences, it would do us all a great deal of good to be more accurate and precise in our terminology. It would also help if lawmakers learned more about the matters on which they create policy.