FDA Warns of Serious Breathing Problems Caused by Gabapentinoids

By Pat Anson, PNN Editor

The U.S. Food and Drug Administration is warning that serious breathing problems can occur in patients who use gabapentin or pregabalin with opioids or other drugs that depress the central nervous system. The elderly and patients with lung problems are at higher risk when they use the drugs, according to an FDA drug safety communication.

The advisory is the latest in a series of warnings about gabapentinoids, a class of nerve medication increasingly prescribed as an alternative to opioid painkillers. There are growing reports of gabapentinoids being abused or raising the risk of overdose and suicide.

“Reports of gabapentinoid abuse alone, and with opioids, have emerged and there are serious consequences of this co-use, including respiratory depression and increased risk of opioid overdose death,” Douglas Throckmorton, MD, deputy director for Regulatory Programs in the FDA’s Center for Drug Evaluation and Research, said in a statement.

“In response to these concerns, we are requiring updates to labeling of gabapentinoids to include new warnings of potential respiratory depressant effects. We are also requiring the drug manufacturers to conduct clinical trials to further evaluate the abuse potential of gabapentinoids, particularly in combination with opioids, with special attention being given to assessing the respiratory depressant effects.”

Gabapentinoid products include gabapentin, which is marketed under the brand name Neurontin, and pregabalin, which is marketed as Lyrica. Generic versions of the drugs are also available.

Gabapentinoids were originally developed to prevent seizures, but their use has tripled over the past 15 years. The drugs are approved to treat a variety of chronic pain conditions, such as fibromyalgia, neuropathy and shingles. They are also widely prescribed off-label.

According to the FDA, over 13 million people filled a prescription for gabapentin in 2016, while over 2 million patients were prescribed pregabalin. Nearly one in five of those patients were also taking opioids.

“Pairing an opioid with any CNS depressant – a gabapentinoid, benzodiazepine, sedating antidepressant, sedating antipsychotic, antihistamine, or other product – will increase the risk of respiratory depression. Shifting treatment from one CNS depressant to another may pose similar risks,” the FDA said.

A Dozen Deaths

The agency said it received 49 case reports of serious breathing problems in patients taking gabapentinoids, including 12 people who died from respiratory depression. It’s advising doctors, caregivers and patients taking gabapentinoids to be alert for signs of confusion, disorientation, dizziness, sleepiness, slow or shallow breathing, unresponsiveness, or bluish-colored lips, fingers and toes.

A 2018 study by Australian researchers found that gabapentinoids often had side effects such as drowsiness, dizziness and nausea. Another study found that combining gabapentin with opioids significantly raises the risk of dying from an overdose. And a recent analysis of calls to U.S. poison control centers found a significant increase in suicide attempts involving gabapentin.

There have also been increasing reports of gabapentin and pregabalin being abused by illicit drug users, who have learned they can use the medications to heighten the high from heroin, marijuana, cocaine and other substances.

A recent study published in JAMA Internal Medicine found little evidence that gabapentinoids should be used off-label to treat pain and said their effectiveness was often exaggerated by prescribing guidelines. The CDC’s 2016 opioid guideline recommends gabapentin and pregabalin dozens of times as alternatives to opioids, without saying a word about their abuse or side effects.

“Our goal in issuing today’s new safety labeling change requirements is to ensure health care professionals and the public understand the risks associated with gabapentinoids when taken with central nervous system depressants like opioids or by patients with underlying respiratory impairment. However, we do not want to unintentionally increase opioid use by turning prescribers away from this class of pain medications,” Throckmorton said.

Panel Recommends Opioid Guidelines for Acute Pain Conditions

By Pat Anson, PNN Editor 

The National Academies of Sciences, Engineering and Medicine (NASEM) is recommending that new clinical guidelines be developed for the treatment of short-term acute pain to reduce the risk of excess opioid prescribing.  

A 247-page report released by NASEM cites a lack of guidance on the appropriate type, strength and amount of opioid medication that should be prescribed to patients in acute pain, and claims that many patients are sent home with more pills than they need, which can later be misused. 

“Clinicians who prescribe opioids have to balance two distinct goals: relieving a patient’s severe pain, while minimizing the potential public health harms of opioid misuse and the resulting emotional distress to families and communities,” said Bernard Lo, president of the Greenwall Foundation and chair of a NASEM committee that wrote the report.  

The 15-member panel is composed primarily of academic, government and medical professionals. No pain sufferers or patient advocates served on the committee and the report gives no indication they were consulted with.    

NASEM is a private, nonprofit institution that was contracted by the FDA in 2018 to study the treatment of acute pain and develop a framework for new clinical guidelines.

Unlike the CDC’s controversial 2016 opioid guideline, which applies to a broad range of chronic pain conditions, NASEM is recommending that guidelines be developed for specific medical conditions or procedures that result in acute pain lasting less than 90 days. 

High-priority surgical procedures include cesarean (C-section) delivery, total knee replacement and wisdom tooth removal. Acute pain conditions such as low back pain, sickle cell disease, migraines and kidney stones are also considered top priorities for opioid guidelines.  

“There are still too many prescriptions written for opioid analgesics for durations of use longer than are appropriate for the medical need being addressed,” Janet Woodcock MD, Director  of the FDA Center for Drug Evaluation and Research, said in a statement.  

“The FDA’s efforts to address the opioid crisis must focus on encouraging ‘right size’ prescribing of opioid pain medication as well as reducing the number of people unnecessarily exposed to opioids, while ensuring appropriate access to address the medical needs of patients experiencing pain severe enough to warrant treatment with opioids.” 

‘Opioids Commonly Overprescribed’

The CDC guideline was only intended for primary care physicians treating chronic pain, but has been widely implemented throughout the healthcare system by other federal agencies, insurers, states and hospitals. Emergency room physicians are reluctant to prescribe opioids for trauma injuries and some patients recovering from surgery are being treated with Tylenol.    

The NASEM report suggests those efforts haven’t gone far enough. 

“Despite widespread efforts over the last five years to reduce opioid prescribing, opioids are commonly overprescribed for acute pain. In addition, the amount of opioids prescribed for acute pain varies by provider, hospital, and geographical region,” NASEM found. 

The report claims that post-surgical patients consume only half of the opioids prescribed to them, and between 6 percent and 14 percent of patients who receive opioids after surgery or in the emergency room continue to use them six to 12 months later. 

Those claims are at odds with a large Mayo Clinic study found that only about 1% of patients given opioids in emergency rooms went on to long term use. Another large study conducted by Harvard Medical School found less than 1% of patients being treated with opioids for post-surgical pain were later diagnosed with opioid misuse.  

Guidance Gaps

The NASEM report identifies several gaps in current guidelines for acute pain and recommends more research on nonopioid alternatives, outcomes of opioid prescribing on different patient populations, and the amount of opioids prescribed and leftover after treatment. 

As PNN has reported, the CDC is already in the initial stages of updating its 2016 guideline to include recommendations for treating acute pain and how to taper patients safely off opioids. The update likely won’t be completed until late 2021. 

An FDA spokesman described the work of the two agencies as complementary and with similar objectives.   

“We acknowledge the work CDC has taken in developing federal guidelines on pain management and the use of opioids, which are based on expert opinion. Our work seeks to build on that work by generating evidence-based guidelines where needed,” Nathan Arnold said in an email to PNN. 

“The guidelines we generate would be distinct from this corresponding effort by the CDC, in that our effort would be indication-specific, and would be based on prospectively gathered evidence drawn from evaluations of clinical practice and the treatment of pain. Our work could potentially inform drug labelling. These two efforts are highly complementary and serve adjacent goals.” 

One of the co-authors of the CDC guideline is involved in both efforts. Roger Chou, MD, a primary care physician and professor at Oregon Health & Science University School of Medicine, served on the NASEM committee.  Chou is also directing research on three CDC-funded studies on opioid and non-opioid treatments for chronic pain, as well as a fourth study on acute pain treatment. Those studies will be used by CDC to update its current guideline.

Chou recently collaborated with Physicians for Responsible Opioid Prescribing (PROP), an influential anti-opioid activist group that seeks drastic reductions in the use of opioid medication. Chou co-authored an article with PROP President Dr. Jane Ballantyne and PROP board member Dr. Anna Lembke that encourages doctors to taper “every patient receiving long term opioid therapy.”

Health Risks of NSAIDs Led to ‘Significant Under-Treatment of Pain’

By Pat Anson, PNN Editor

The opioid crisis has been blamed on a lot of things, everything from pharmaceutical marketing to poor medical education to an epidemic of despair.

Now we can also blame NSAIDs.

A new study by researchers at Boston University School of Public Health (BUSPH) found that a decline in prescriptions for non-opioid analgesics — mostly non-steroidal anti-inflammatory drugs and COX-2 inhibitors -- coincided with a marked increase in opioid prescribing for people with chronic musculoskeletal pain.

Concerns about the cardiovascular side effects of Vioxx and other COX-2 inhibitors first came to light in the early 2000s. More was also being learned about heart disease, strokes and gastrointestinal problems associated with NSAIDs.

"While the opioid epidemic is complex and has many possible causes, our findings suggest that health risks associated with NSAIDs were one factor that led to increased prescribing of opioids," says lead author Dr. Andrew Stokes, assistant professor of global health at BUSPH.

Stokes and his colleagues looked at 1999-2016 prescription data for over 7,200 U.S. adults with back pain, neck pain or arthritis. Increases in opioid prescriptions matched the decrease in prescribing for non-opioid analgesics (predominantly NSAIDs and COX-2 inhibitors) between 2003 and 2006.

"We realized that the point at which increasing opioid prescriptions crossed over with the decrease in non-opioid prescriptions occurred when the cardiovascular risks of COX-2 inhibitors led to rofecoxib (Vioxx) coming off the market. The gastrointestinal risks of NSAIDs were also well-recognized by then,” says senior author Dr. Tuhina Neogi, a professor of epidemiology at BUSPH and Chief of Rheumatology at Boston Medical Center.

“Thus it appeared to us that an increase in opioid prescribing during that time was, at least in part, an unintended consequence of COX-2 inhibitors coming off the market and concerns about NSAID risk.”

‘Unmet Need for Pain Management’

The study, published in JAMA Network Open, also found that growing recognition of the opioid crisis after 2013 led to decreases in opioid and non-opioid analgesic prescriptions for people with chronic musculoskeletal pain, particularly among those with less education and lower socioeconomic status.

"Care is needed to ensure that our response to the opioid crisis does not leave people living with chronic pain behind. The abrupt decline in prescribing to those of low socioeconomic status is concerning given that these same individuals also face the greatest barriers to accessing alternative pain treatments, such as physical therapy," Stokes says.

"There's so much talk now about transitioning people away from opioids. But if that's happening without considering the barriers to non-pharmacologic treatments, there may be a significant problem of under-treatment of pain," adds study co-author Dielle Lundberg, a research fellow at BUSPH.

Between 2013 and 2106, researchers found an 11% decrease in prescriptions for both opioid and non-opioid pain relievers, suggesting a significant amount of pain was going untreated.

“Care is needed to ensure that our response to the opioid crisis does not leave people living with chronic pain behind.”

— Dr. Andrew Stokes

“The fact that the present study was restricted to patients with potential needs for pain management also raises the concerning possibility that an unmet need for pain management has increased over this period. Such a trend would be alarming given evidence that untreated chronic pain may prompt patients with chronic pain to seek out illicit heroin or fentanyl,” researchers concluded.

“In addition, several recent studies based on data from the National Violent Death Reporting System have found a high rate of chronic pain among suicide decedents, and recent research and commentary on opioid discontinuation have suggested that recent increases in the suicide death rate may be linked to changes in pain treatment.”

U.S. Facing ‘Syndemic’ of Opioid Overdoses

By Pat Anson, PNN Editor

The U.S. opioid crisis is a lot more complex than many people think. Instead of a single “epidemic” fueled by prescription opioids, researchers say there are three types of opioid epidemics occurring in different parts of the country simultaneously.

A team of researchers at Iowa State University studied death certificate data from all 3,079 counties in the lower 48 states and found distinct regional differences in the opioids that caused the most overdoses.

Cities in New England have been hit hard by illicit fentanyl and other synthetic opioids; the Rockies and Midwest are plagued by heroin; and a prescription opioid epidemic still lingers in many rural counties in the South and West.

A fourth epidemic – dubbed a “syndemic” by researchers – involves multiple drugs and exists in counties where the opioid crisis first erupted, particularly in mid-sized cities in Kentucky, Ohio and West Virginia. 

About 25 percent of all U.S. counties fall into one of these epidemic categories.   

“Our results show that it’s more helpful to think of the problem as several epidemics occurring at the same time rather than just one,” said co-author David Peters, PhD, an associate professor of sociology at Iowa State University. “And they occur in different regions of the country, so there’s no single policy response that’s going to address all of these epidemics. There needs to be multiple sets of policies to address these distinct challenges.”

LEADING CAUSE OF OPIOID OVERDOSES

Overdose deaths linked to prescription opioids peaked nationwide in 2013 and have fallen in recent years. But researchers say some counties with poor economies continue to struggle with prescription drugs. Over one-third of the counties in Tennessee, Oklahoma, Nevada and Utah fall into this category.

“We find that prescription-related epidemic counties, whether rural or urban, have been ‘left behind’ the rest of the nation. These communities are less populated and more remote, older and mostly white, have a history of drug abuse, and are former farm and factory communities that have been in decline since the 1990s. Overdoses in these places exemplify the ‘deaths of despair’ narrative,” researchers reported in the journal Rural Sociology.

“By contrast, heroin and opioid syndemic counties tend to be more urban, connected to interstates, ethnically diverse, and in general more economically secure. The urban opioid crisis follows the path of previous drug epidemics, affecting a disadvantaged subpopulation that has been left behind rather than the entire community.” 

The study found heroin overdose deaths clustered along two major corridors, one linking El Paso to Denver and another linking Texas and Chicago. Those findings correspond with known drug routes used by cartels smuggling heroin into the U.S. from Mexico.

The study only looked at death certificate data up to 2016, missing the full impact of the CDC opioid guideline, as well as the widening scope of the fentanyl and counterfeit drug crisis. As PNN has reported, hundreds of people have died on the west coast this year after ingesting counterfeit oxycodone laced with fentanyl.

“We are waiting to obtain the 2017 and 2018 data from CDC, but I expect the number of Rx opioid epidemic counties have transitioned to the synthetic+Rx epidemic and the opioid syndemic,” Peters told PNN in an email. “Fentanyl mixtures are replacing Rx pills and heroin in many places, mainly because fentanyl analogs are cheap to produce and generate more profits for drug traffickers.”

Given the expanding nature of the opioid crisis, Peters and his colleagues say tighter regulation of opioid prescribing and dispensing will have little effect on overdoses. The same is true for law enforcement efforts to stop drug traffickers and smuggling.

Instead they recommend expanding access to addiction treatment, as well as long-term investment in struggling communities to reduce both economic despair and the demand for drugs.  

Severely Injured? Don’t Count on Getting Opioid Pain Medication

By Madora Pennington, PNN Columnist

When I went to Cedars-Sinai Urgent Care in Los Angeles recently, screaming and crying, my blood pressure dangerously high, my foot ballooning and turning blue from a household accident, the doctor wouldn’t give me opioid pain medication.

They x-rayed my foot. Two bones were broken. They gave me a shot of a NSAID that, they said, would wear off in a few hours. It did. They gave me crutches, a boot to immobilize my foot, suggested I see a surgeon and, in the meantime, take Advil. What?

It wasn’t personal. This is Cedars-Sinai’s policy. In urgent care, they won’t give opioids to anyone for any reason.

I had gone to Cedars-Sinai because I have a complex medical history. There, my records are most complete. This makes the appointment easier for the doctor and me.

Also in my records is my long-term opioid use history. I was on Vicodin and morphine daily for about six years, to treat chronic pain from Ehlers-Danlos syndrome, a rare genetic disorder that causes all the joints to be loose, or rather, permanently sprained.

When I started on daily opioids, an option no longer available, I had pain that I could not live with, no quality of life and was planning my suicide.

Those drugs gave me enough relief to endure. I became less of a burden to my caretaker. I could focus on trying to improve my health. If your day is spent fighting extreme pain, being productive is not possible.

Then I got very lucky.

In 2014, experimental treatment had improved the strength of my tendons and ligaments. My body hurt less. I went straight off the opioids and stayed off.

Withdrawal was a harrowing marathon of torture. For years after, I suffered from the physical damage opioids left behind. But I didn’t go back on them because I had never become addicted. Why? I had been warned at the start of my opioid treatment to take the drugs for physical pain only, not for emotional relief. This patient follows orders.

As a result of the war on opioids, many chronic pain patients are being denied adequate pain relief. Some forced to taper end up committing suicide from the agony of withdrawal plus untreated pain. This became such a problem, the U.S. Department of Health and Human Services issued new recommendations in October, advising doctors to look at each case individually and not to put patients on rapid opioid tapers or abruptly discontinue them.

But I had never heard of someone with a severe, acute injury forced to suffer. Even I can’t be trusted? I have a proven record of responsible opioid use with no addiction.

The doctor treating my injured foot, clearly embarrassed, told me, “This is urgent care. If it’s something severe, the patient should be in the ER or at a pain doctor.”

But I had called before I came. “Would they see me for a possibly broken foot?”

The receptionist said to come in, they would x-ray me right away. She didn’t say I would not be given adequate pain medication.

Has the war on opioids gone too far? If doctors and hospitals are too afraid of lawsuits or prosecution to prescribe, then yes.

A Mayo Clinic study found that only about 1% of patients given opioids in emergency rooms went on to long term use. Another study found less than 1% of patients being treated with opioids for post-surgical pain developed dependence or abused opioids. Does that mean the other 99% of us should not get pain medication?

Not according to the CDC, which suggests three days of opioids for acute injuries like mine.

After I left urgent care that day, I took Vicodin which had expired a year before but I’d never gotten rid of. If it hadn’t worked, I would have had to call an ambulance and gone to the ER that night, just for pain treatment.

After surgery, the podiatrist told me, “One bone was in pieces. I bolted together what I could. Some bits were too small so I picked them out and threw them away.” Well, that explains the pain I’d been in.

I vowed never to leave things on the floor that someone might trip on. And I set up Google Home to process a command to make a phone call for help.

I also filed a complaint with the state against the doctor. Medical care is about the patient, not hospital bureaucrats.

Madora Pennington writes about Ehlers-Danlos and life after disability at LessFlexible.com. Her work has also been featured in the Los Angeles Times.

Opioids Are Not the Only Pain Meds That Can Be Abused

By Dr. Lynn Webster, PNN Columnist

Contrary to popular opinion, opioids don't cause substance abuse. Opioids certainly may be abused, but it is human biology itself that drives drug abuse.

We often get the message that any other pain treatment would be better than using opioids. However, even non-opioids prescribed for pain can contribute to overdoses and suicides. The same genetic and environmental factors that cause opioid abuse can induce abuse of other drugs, too.

For several years the number of opioid prescriptions has declined significantly, due to public demand and political pressure. According to the IQVIA Institute, there was a 17 percent decrease in the number of opioids prescribed in 2018 alone.

We may have expected that to translate into fewer drug abuse problems. Instead, we have seen an increase in overdoses, hospitalizations and suicides involving non-opioids such as gabapentin, methamphetamines and muscle relaxants.

Less access to prescription opioids has driven some people in disabling pain to seek illegal alternative medications. That has led to a wave of use and abuse of drugs that doctors have not prescribed.

Between 2016 and 2017, the CDC reported a nearly 47% increase in fentanyl-related deaths. Overdoses related to methamphetamine and cocaine have also surged.  

According to Stateline, approximately 14,000 cocaine users and 10,000 meth users died in the United States in 2017, triple the number of deaths in 2012. Deaths involving have heroin also spiked since 2010.  

Gabapentin and Baclofen 

Prescription drugs, too, have fueled the negative statistics. Doctors have felt forced to taper or discontinue opioids. In an attempt to find alternatives for pain management, they have increased the number of gabapentin and baclofen prescriptions. 

As PNN has reported, a recent study published in Clinical Toxicology found a “worrying” increase in calls to U.S. poison control centers about gabapentin (Neurontin) and the muscle relaxer baclofen, coinciding with a decrease in opioid prescriptions. The study analyzed more than 90,000 cases of exposure to gabapentin and baclofen, many of which were coded as suicides or attempted suicides.

“Gabapentin and baclofen are two medications that have seen increased availability to patients as alternatives to opioids for the treatment of acute and chronic pain. With greater accessibility, poison center exposures have demonstrated a marked increase in toxic exposures to these two medications,” wrote lead author Kimberly Reynolds of the University of Pittsburgh.

“As poison center data do not represent the totality of cases in the United States, the steep upward trends in reported exposures reflect a much larger problem than the raw numbers would suggest.”  

Gabapentin is one of the most commonly prescribed drugs in the United States. It is prescribed for epilepsy, hot flashes, migraines, nerve damage, and more. It is also used to treat the symptoms of drug and alcohol detoxification, and to treat pain for patients at higher risk of addiction to opioids.  

Baclofen is a muscle relaxant that has also been substituted for opioids. Other non-opioid drugs such as pregabalin and NSAID’s are being increasingly prescribed as well.  

All Medications Have Risks 

Non-opioids have a role to play in pain management, but it is just as important to understand their dangers. While we need effective alternatives to opioids, it is important to know that alternatives also have risks. That is unavoidable, because all medications carry potential benefits and consequences.  

To decide whether a medication is appropriate for an individual, it is critical to determine whether the potential benefit outweighs potential harm. Gabapentin and baclofen are not bad drugs, but they are not harmless replacements for opioids, either.  

No pain medication, whether it is an opioid or non-opioid, is right for everyone under all circumstances. The next time a physician or nurse practitioner suggests replacing an opioid with gabapentin, baclofen, or another medication, it would be appropriate to ask for a comparison of the risks and benefits. 

Talking with your healthcare provider about your preference for a particular medication does not make you a drug seeker. It helps you become an informed patient. 

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

Opinions expressed here are those of the author alone and do not reflect the views or policy of PRA Health Sciences. 

CDC Planning to Update Opioid Guideline in 2021

By Pat Anson, PNN Editor

The Centers for Disease Control and Prevention is in the initial stages of updating or expanding its controversial opioid prescribing guideline, which has been widely blamed for patient suffering, abandonment and suicide since its release in 2016.

CDC officials outlined their plans today at a meeting in Atlanta of the Board of Scientific Counselors (BSC) for the agency’s National Center for Injury Prevention and Control (NCIPC).

The update – which could take two years to complete – is likely to include recommendations for treating short-term acute pain, as well as how to taper patients safely off opioid medication.

Public pressure has been building on the CDC to clarify the guideline. Although voluntary and only intended for primary care physicians treating chronic pain, the guideline’s recommended limits on opioid prescribing have been widely adopted as policy by federal agencies, states, insurers, pharmacies and many doctors.

“Some policies and practices citing the guideline went beyond its recommendations,” said Dr. Deborah Dowell, Chief Medical Officer for NCIPC and co-author of the guideline. “The guideline does not support abrupt tapering or sudden discontinuation of opioids, but has been inappropriately cited to justify hard limits or cutting off opioids.

“In addition, we’ve heard reports of misapplications beyond the guideline’s clearly stated scope. For example, applying the recommendations to patients in cancer treatment or experiencing surgical pain.”

Last year the American Medical Association took a stand against the “misapplication” and “inappropriate use” of the guideline. The Food and Drug Administration has also warned that many patients are being tapered off opioids inappropriately, putting them at risk of withdrawal, uncontrolled pain and suicide.

Although the matter appears urgent, Dowell said the CDC was “just getting started” on updating the guideline. She said updated recommendations would likely not be finalized until late 2021, five and a half years after the initial guideline was released.   

‘Way Too Long to Wait’

During a public comment period, critics called the guideline a failed public health experiment that has done more harm than good.

“No one should have to die in pain. No one should have to live in pain,” said Amber Bullington, an intractable pain patient who was forcibly tapered off opioids. “We need to rescind the CDC guidelines and undo the harm you’ve done. You say you want to save lives. You’re not saving lives. Overdoses continue to escalate. Pain patients are dying and suffering.”   

“I have talked to patients all over the U.S. who are being denied treatment because of the reign of terror that has been established against doctors who try to treat them with opioid prescriptions. This has to stop. This is madness,” said patient advocate Richard “Red” Lawhern.

Others expressed concern about the guideline not being updated until 2021.

“It’s important that something be done in the interim to negate the effect of the misuse of the guideline across the board by so many government agencies,” said Richard, a pain patient and advocate. “Two years is way too long to wait for this to get fixed.”

“Chronic pain patients may not be able to last that long. Many won’t,” said Peter Pischke, a patient advocate. “I beg you guys, keep this in mind. You will have to make it clear and un-vague so that every politician, bureaucrat, administrator, every law enforcement official knows that what you guys tried to do in 2016 failed miserably when it came to patients with cancer and patients with chronic pain.”

The BSC voted unanimously to form a new “Opioid Workgroup” of 12 to 20 people to direct efforts to update the guideline. While a wide range of medical specialties would be represented on the panel, there was no mention of including patients or patient advocacy groups in anything more than an advisory or ad hoc role.

Nominations to serve on the Opioid Workgroup will be accepted until February 4, 2020.

As PNN has reported, the CDC has funded three new studies of opioid and non-opioid treatments for chronic pain. Draft reports are expected to be finalized in early 2020. Two additional studies of treatments for migraine and acute pain were recently awarded to the Mayo Clinic and Oregon Health & Science University, respectively, at a cost of $1.36 million. Results from those studies are not expected until August 2020.

Gabapentin Linked to Growing Number of Suicide Attempts

By Pat Anson, PNN Editor

We’ve reported several times about the abuse and lack of effectiveness of gabapentin, a nerve medication increasingly prescribed to treat fibromyalgia, neuropathy and other types of chronic pain.

It turns out gabapentin is also involved in a growing number of attempted suicides.

In a large new study published in the journal Clinical Toxicology, University of Pittsburgh researchers looked at over 90,000 calls involving medications to U.S. poison control centers. They found that calls about gabapentin and the muscle relaxant baclofen increased significantly just as opioid prescriptions began declining.

“Gabapentin and baclofen are two medications that have seen increased availability to patients as alternatives to opioids for the treatment of acute and chronic pain. With greater accessibility, poison center exposures have demonstrated a marked increase in toxic exposures to these two medications,” wrote lead author Kimberly Reynolds of the University of Pittsburgh.

“As poison center data do not represent the totality of cases in the United States, the steep upward trends in reported exposures reflect a much larger problem than the raw numbers would suggest.”     

Between 2013 and 2017, calls involving the abuse and misuse of gabapentin went up nearly 120 percent, while reports of baclofen being abused or misused rose nearly 32 percent from 2014 to 2017.

Even more concerning is that calls about attempted suicides involving gabapentin rose 80 percent, while calls about attempted suicides with baclofen increased 43 percent. Co-ingestion of sedatives and opioids were common for both medications.

Only 19 deaths involving gabapentin were identified as possible suicides during the five-year study period, but there were thousands of gabapentin-related calls each year coded as attempted suicides — including over 10,000 calls in 2017 alone.

SOURCE: CLINICAL tOXICOLOGY

“It would be anticipated that patients who are prescribed gabapentin and/or baclofen would be more likely to be treated for mood disorders and pain as they are frequently comorbid and therapy overlaps significantly,” researchers said.

“Gabapentin has specifically been recognized for its misuse and diversion potential, synergistic effect with opioid use, and contribution to use disorders. Baclofen misuse has not been as frequently described but is anecdotally observed and associated with severe toxicity, physical dependence, and complicated withdrawal.”

Gabapentin was the 10th-most widely prescribed drug in the U.S. in 2017. Calls to poison control centers about gabapentin were highest in Kentucky and West Virginia, two of the states hardest hit by the opioid crisis. Calls about baclofen were highest in Kentucky, Maine and New Mexico.

The researchers recommend that patients who are prescribed gabapentin or baclofen be prescreened for substance use disorders, mood disorders and suicidal ideation.

FDA Gabapentin Warning

The Food and Drug Administration warned in 2008 that all patients being treated with gabapentin or ten other antiepileptic drugs should be informed about the risks of suicidal thoughts and actions.

The FDA reviewed 199 clinical trials of the drugs and found that patients who received them had almost twice the risk of suicidal behavior or ideation (0.43%) than patients on a placebo (0.24%). That means there would be one additional case of suicidal thinking or behavior for every 530 patients treated with an antiepileptic drug.

“All patients who are currently taking or starting on any antiepileptic drug for any indication should be monitored for notable changes in behavior that could indicate the emergence or worsening of suicidal thoughts or behavior or depression,” the FDA said.

Gabapentin (Neurontin) and its chemical cousin pregabalin (Lyrica) belong to a class of nerve medication called gabapentinoids. Both drugs were originally developed to treat epileptic seizures, but are now widely prescribed off label to treat a variety of chronic pain conditions.    

A recent Swedish study found that patients taking gabapentinoids had higher rates of overdose, suicide and suicidal behavior than the general population. The risks were strongest in teens and young adults.

A recent clinical review found little evidence that gapapentinoids should be used off-label to treat pain and that prescribing guidelines often exaggerate their effectiveness. The CDC’s controversial 2016 opioid guideline, for example, calls gabapentin and pregabalin “first-line drugs” for neuropathic pain.

In a new draft report being funded by the CDC, researchers say gabapentin showed only “small improvements” in pain for people with diabetic peripheral neuropathy and fibromyalgia. The study by the Agency for Healthcare Research and Quality (AHRQ) is expected to finalized in early 2020.

CDC Considering ‘Update or Expansion’ of Opioid Guideline

By Pat Anson, PNN Editor

When the Centers for Disease Control and Prevention released its controversial opioid prescribing guideline in March 2016, it pledged to study the impact of the guideline on patients, doctors and pain treatment in the United States.

“CDC is committed to evaluating the guideline to identify the impact of the recommendations on clinician and patient outcomes, both intended and unintended, and revising the recommendations in future updates when warranted,” the agency said.

Three and a half years later, after widespread reports of patient suffering, abandonment and suicide, the CDC may finally be getting around to an update. But it may not be what patients and doctors were hoping for.

In a meeting next week of the Board of Scientific Counselors (BSC) for the CDC’s National Center for Injury Prevention and Control (NCIPC), guideline co-author Dr. Deborah Dowell is scheduled to give a 30-minute presentation entitled “Background for Updating the CDC Guideline for Prescribing Opioids.”

According to the agenda for the December 4 meeting in Atlanta, Dowell’s presentation will be preceded by an update from NCIPC Director Dr. Debra Houry, who oversaw development of the opioid guideline. Presentations are also planned on overdose prevention and the formation of an “Opioid Workgroup.”

“CDC is scheduled to give a background presentation for a potential update/expansion of the CDC Guideline,” Courtney Lenard, a CDC spokesperson, said in an email to PNN. “CDC will also request that NCIPC’s BSC establish an Opioid Workgroup to provide expert input and observations on a possible update or expansion of the guideline.”

Public pressure has been building on the CDC to clarify the guideline — but not to expand it. Although voluntary and only intended for primary care physicians treating chronic pain, the guideline’s recommended limits on opioid prescribing have been widely adopted as policy by federal agencies, state governments, insurers, pharmacy chains and many doctors.

The guideline has also been applied to short-term acute pain situations, such as patients being treated for post-surgical pain or emergency room trauma. Last year, CDC Director Dr. Robert Redfield said he wanted the agency to develop opioid prescribing guidelines for acute pain and to use a new enhanced data system to track overdoses in hospital emergency rooms.

“I hope this does not become CDC Prescribing Guideline 2.0. In the original CDC Guideline, the identity of the key expert group was unknown, there were concerns over conflict of interest and secrecy, and legislatures or regulatory agencies eventually adopted the guideline and treated it as gospel despite the limitations stated in the report,” said Stephen Ziegler, PhD, a Professor Emeritus at Purdue University.

Last year the American Medical Association took a stand against the “misapplication” and “inappropriate use” of the guideline -- and adopted a resolution stating that some patients “can benefit from taking opioids at greater dosages than recommended by the CDC.”   

In April, the Food and Drug Administration warned that many patients were being tapered off opioids inappropriately, putting them at risk of withdrawal, uncontrolled pain and suicide. That was followed days later by a pledge from Redfield to re-evaluate the guideline and “clarify its recommendations.”

A clarification is long overdue. In a PNN survey early this year of over 6,000 pain patients and healthcare providers, an overwhelming majority said the guideline was harmful to patients and should be revised.

“Cannot understand or know why the CDC will not speak out on the harm done to undertreated, denied and abandoned patients,” one patient told us.

“The guidelines were written in secret, and the carnage that we predicted has come to pass,” said an emergency medicine physician.

“They should be revoked. People are suffering and committing suicide due to inability to tolerate suffering. This is inhumane,” another provider wrote. “It blemishes CDC’s reputation.”

CDC Funding AHRQ Studies

Instead of getting input from doctors and patients on the impact of the guideline, the CDC appears to be focused on more research to help expand its use. PNN has learned that the CDC is funding three new studies on the effectiveness of opioid and non-opioid therapies — essentially doubling down on previous research that found little evidence that opioids are effective for chronic pain.    

“CDC is funding the Agency for Healthcare Research & Quality (AHRQ) through an interagency agreement to conduct systematic reviews of new scientific evidence that has been published since the Opioid Prescribing Guideline was released,” said CDC’s Lenard. “The reviews will evaluate the effectiveness and comparative effectiveness of opioids, non-opioid pharmacologic therapy, and nonpharmacologic therapy for chronic and acute pain.

“Results of these reviews will help CDC determine whether evidence gaps have been addressed and if the Opioid Prescribing Guideline should be updated or expanded. If a Guideline update or expansion occurs, the development process would include consideration of findings from the systematic reviews and an additional public comment period through the Federal Register once an update or expansion is drafted.”

All three AHRQ studies were awarded on the same day – at an estimated cost of $1.1 million – to the Pacific Northwest Evidence-based Practice Center at Oregon Health & Science University, which is headed by Dr. Roger Chou, one of the co-authors of the CDC guideline.

As PNN has reported, Chou is a primary care physician and longtime researcher who has publicly aligned himself with Physicians for Responsible Opioid Prescribing (PROP), an influential anti-opioid activist group that seeks drastic reductions in the use of opioid medication.  

Chou recently co-authored an article with PROP President Dr. Jane Ballantyne and PROP board member Dr. Anna Lembke that encourages doctors to consider tapering “every patient receiving long term opioid therapy.”

Chou also consulted with PROP founder Dr. Andrew Kolodny and other PROP members for Oregon Pain Guidance, an advisory group that claims opioid tapering “will improve the quality of life for the majority of patients.”

DR. ROGER CHOU

It is not clear if PROP members are also involved in the three AHRQ studies, as they were in drafting the CDC guideline. But critics say Chou’s continuing association with PROP raises questions about his impartiality as a researcher.

“For years, we have called out a ‘False Narrative’ that prescription opioids drive the current overdose crisis; current data shows this is demonstrably false,” said Dr. Chad Kollas, a palliative care specialist in Florida. “We have not done as well calling out a “Hidden Narrative,” where PROP-affiliated physicians have wrongly influenced and encouraged the misapplication of federal policy in a way that has systematically harmed vulnerable patients in pain. We must call out their conflicts of interest loudly now.”

As a matter of policy, AHRQ does not release conflict of interest statements or disclose the names of its consultants, investigators and peer reviewers until after its reports are finalized. The AMA is recommending that the agency end that policy.

“We would suggest that AHRQ publish the list of all those involved in any aspect of the report… to help remove any perception of potential conflict,” Dr. James Madara, the AMA’s Executive Director and CEO, wrote in a letter to AHRQ. The letter also urges the agency to clearly state that the opioid epidemic was not fueled by prescription opioids and that its research should not be used to justify tapering.

Draft versions of the three AHRQ studies have been completed and were recently posted for 30 days on the agency’s website. They were removed after a public comment period ended, which is another AHRQ policy. Fortunately, PNN was able to obtain copies before the draft reports were withdrawn from public view.

• Opioid Treatments for Chronic Pain

• Nonopioid Pharmacologic Treatments for Chronic Pain

• Nonpharmacologic Treatment for Chronic Pain

What did Chou and his researchers conclude? The three draft reviews support many of the same conclusions as the CDC guideline — hardly a surprise since Chou helped write the guideline.

“For patients with chronic pain, opioids are associated with small beneficial effects versus placebo but are associated with increased risk of short-term harms and do not appear to be superior to nonopioid therapy. Evidence on intermediate-term and long-term benefits remains very limited and additional evidence confirms an association between opioids and increased risk of serious harms,” one draft says. 

“Findings of this review, with expansion of scope to include short-term trials, support the recommendation in the 2016 CDC guideline that opioids are not first-line therapy for chronic pain and to preferentially use nonopioid alternatives.”    

The AHRQ expects to release final versions of the three pain management reports in early 2020. A list of experts and informants will be released at that time, along with any conflicts of interest. 

Still unclear is what the CDC will do with the reports and what kind of “update or expansion” the agency is considering for its opioid guideline.

U.S. Life Expectancy Still Declining

By Pat Anson, PNN Editor

After decades of progress with Americans living longer and healthier lives, a disturbing new study has documented how life expectancy in the U.S. has declined for three consecutive years.

The drop in life expectancy was most pronounced in young and middle-aged adults. Starting in 2014, midlife mortality increased across all racial groups, largely due to drug overdoses, alcohol abuse, suicide, and chronic illnesses such as hypertension and diabetes. Researchers said prescription opioids were more of a symptom than a cause of premature deaths.

In 2014, Americans were expected to live to 78.9 years of age. By 2017, the average life expectancy had fallen to 78.6 years.

The U.S. now has the worst midlife mortality rate among 17 high income countries, even though it spends more on healthcare per capita than any other nation.  

“This is an emergent crisis. And it is a uniquely American problem since it is not seen in other countries. Something about life in America is responsible,” lead author Steven Woolf, MD, reported in a Special Communication published in JAMA.

The largest increases in midlife mortality occurred among adults with less education and those living in rural areas.  Changes in life expectancy were greatest in upper New England, the Ohio Valley, and Appalachia – regions where economic distress, lower social mobility and the so-called epidemic of despair contributed to rising rates of suicide and drug and alcohol abuse.

“While it’s a little difficult to place the blame on despair directly, the living conditions causing despair are leading to other problems,” said Woolf, who is director emeritus of the Center on Society and Health at Virginia Commonwealth University. “For example if you live in an economically distressed community where income is flat and it’s hard to find jobs, that can lead to chronic stress, which is harmful to health.”

While life expectancy increased in a handful of Western states, midlife mortality rose in Ohio and West Virginia – states often called ground-zero of the opioid crisis.  A sharp increase in opioid overdoses came in three waves; starting with the introduction of OxyContin and the overuse of prescription opioids in the 1990s, followed by increased heroin use, and then the emergence of illicit fentanyl – which triggered another wave of opioid overdoses starting in 2013.

“However, the increase in opioid-related deaths is only part of a more complicated phenomenon and does not fully explain the increase in midlife mortality rates from other causes, such as alcoholic liver disease or suicides. Opioid-related deaths also cannot fully explain the U.S. health disadvantage, which began earlier (in the 1980s) and involved multiple diseases and nondrug injuries,” Woolf said.

The tsunami of fentanyl overdoses has yet to dissipate. According to a new study by the Massachusetts Department of Public Health, 93% of opioid related overdoses in the state in the first nine months of 2019 involved fentanyl. Deaths involving prescription opioids such as oxycodone and hydrocodone peaked in 2014 and are now linked to only about 10% of overdose deaths in Massachusetts.

FDA Approval Gives New Hope to Patients With Rare Genetic Disease

By Pat Anson, PNN Editor

Lisa Kehrberg was once frightened about her future. For years the retired family practice doctor and mother of two would suffer severe bouts of unexplained abdominal pain, headaches and nausea that would leave her hospitalized for weeks at a time.

“I was doubled over, rocking, vomiting and crying with the worst pain of my life. Worse than labor, appendicitis, or anything else I'd experienced. It was a hot, burning pressure that was like lava and hot razor blades filling up my abdomen,” Lisa recalled.

She was eventually diagnosed with a rare genetic disease called acute intermittent porphyria, which causes toxic molecules to build up in the body. The same disease killed Lisa’s brother in 2011. And she thought the same fate awaited her.

“One of the most common causes of death from porphyria is suicide. This isn't surprising. I always wonder how people who are sick like me keep surviving. To live in continuous excruciating pain every minute of every day with no end in sight is quite the challenge,” Lisa wrote in a 2016 column for PNN.

It was about that time that Lisa entered a clinical trial program. Every four weeks she’d travel to Houston from her home near Chicago for injections of an experimental drug. Over time, her symptoms began to improve and the porphyria attacks that used to occur monthly became less frequent.

LISA KEHRBERG, MD

Like other participants in clinical studies, Lisa wasn’t allowed to talk publicly about the drug she was getting – until now.  

The Food and Drug Administration has just approved the use of Givlaari (givosiran) for the treatment of adult patients with acute hepatic porphyria (AHP). Approval was granted based on results from placebo controlled trials involving 94 porphyria patients. Those who received Givlaari experienced 70% fewer porphyria attacks compared to patients receiving a placebo.  

“Prior to getting givosiran I was bed-bound for close to 6 months straight from severe muscle weakness and paralysis issues. I no longer have paralysis and most of the muscle weakness has resolved,” Lisa said in an email. “The rate of new attacks has decreased greatly, finally giving my nerves a chance to heal after 22 years of attacks and 6 years of back-to-back attacks.”

“These attacks occur suddenly and can produce permanent neurological damage and death,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence, said in a statement Wednesday. “Prior to today’s approval, treatment options have only provided partial relief from the intense unremitting pain that characterizes these attacks. The drug approved today can treat this disease by helping to reduce the number of attacks that disrupt the lives of patients.”

The FDA approved Givlaari under its breakthrough therapy, priority review and orphan drug designations, which provide incentives to companies in the development of drugs for rare diseases. Approval was granted to Alnylam Pharmaceuticals, which expects Givlaari to be available to healthcare providers by the end of the year.

There are about 3,000 people diagnosed with active porphyria in the U.S. and Europe. Due the wide array of symptoms the disease has, it can take years before an accurate diagnosis is made.

“The FDA approval of Givlaari is an important milestone for our community, as we now have a new treatment option for adults living with acute hepatic porphyria,” said Kristen Wheeden, Executive Director of the American Porphyria Foundation.

Image courtesy of Alnylam Pharmaceuticals

“AHP can have a profound impact on the lives of patients and their families. Porphyria attacks are associated with severe, incapacitating pain, often requiring hospitalization for management. In addition, many patients struggle on a daily basis with chronic symptoms related to their disease. The approval of Givlaari is exciting for our community.”

Lisa Kehrberg isn’t out of the woods just yet. She has permanent nerve damage from years of porphyria attacks. But her future is a lot brighter than it was.  

“For newly diagnosed patients, I strongly believe this treatment has the ability to stop the progression of the disease and will allow patients to lead a normal, functional life,” she says. 

Little Evidence to Support Rescheduling of Tramadol

By Roger Chriss, PNN Columnist

The consumer watchdog group Public Citizen has petitioned the FDA and DEA to “upschedule” the opioid painkiller tramadol. The DEA set tramadol as a Schedule IV drug in 2014, and the petition urges moving it to a more restrictive Schedule II, on the same risk level as hydrocodone and oxycodone.

The petition claims that tramadol is “an increasingly overprescribed, addictive, potentially deadly narcotic.” But the basis for this claim and the assumption that upscheduling will help are problematic.

The CDC reports that there were approximately 1,250 fatal overdoses involving tramadol in 2017, the most recent year for which data is available. Like most fatal overdoses, tramadol deaths often involve multiple drugs, so it’s hard to draw any conclusions from those deaths.

Tramadol is complex, with a highly variable patient response. Some patients have such a strong negative reaction to the drug that they refuse to take it again. Others find it too sedating at high doses or too weak to provide adequate pain relief. Abuse, addiction and overdose can also occur with tramadol.

Recently Harvard Health looked at a JAMA study on the risks of using tramadol versus other pain relievers. Tramadol was found to have a higher risk of death than anti-inflammatory medications such as naproxen (Aleve), while people treated with codeine had a similar level of risk.

“However, because of the study’s design, the researchers could not determine whether tramadol treatment actually caused the higher rates of death. In fact, the patients for whom tramadol is prescribed could make it look riskier than it truly is,” said Robert Shmerling, MD, an editor at Harvard Health.

Unintended Effects of Upscheduling

Understanding the effects of upscheduling is tricky. In 2014 the DEA reclassified hydrocodone (Vicodin) from Schedule III to the more restrictive Schedule II. The reclassification accelerated a trend that was already underway – hydrocodone prescriptions had been falling since 2011.

But there were unintended consequences to upscheduling. A recent University of Texas study found that decreases in hydrocodone prescribing after its rescheduling “were larger in patients being treated for cancer.”

Anotherr study found that upscheduling led to a substantial decrease in hydrocodone prescribing in hospital emergency departments, but that was offset by an increase in prescriptions for codeine and anti-inflammatory drugs.

Upscheduling hydrocodone has also had a negligible effect on overdoses, which are largely caused by illicit fentanyl, heroin and other street drugs, as well as non-opioid medications such as Xanax.

Similarly, predicting the impact of new prescription opioids is difficult. Breathless warnings about the opioid Zohydro, which was approved as a Schedule II drug in 2014, proved false. “There was no great surge of overdoses” after Zohydro was introduced, as Chris MacGreal wrote in his book “American Overdose.”

Fears about opioids are also delaying the introduction of safer medications. The experimental opioid NKTR-181 has less abuse potential than traditional opioids, but its approval is uncertain because the FDA has stopped all advisory committee meetings on opioid analgesics.

Public Citizen ignores all this. It also fails to mention other actions the FDA could pursue, from making naloxone into an over-the-counter drug to improving access to medication-assisted therapy for opioid use disorder. There’s no petition to have the DEA “nix the wavier” for buprenorphine (Suboxone) to make it more widely available or to have the federal government promote the Pain Management Best Practices Inter-Agency Task Force report.

Finally, there’s no call to monitor outcomes. As PNN has reported, opioid tapering has had tragic unintended consequences. And a new Cochrane review on the effects of educational and regulatory efforts targeting prescribers was unable to draw any conclusions “because the evidence is of very low certainty.” The authors could find only two relevant studies that assessed prescribing policies adopted in the 1990’s.

There are good reasons to be cautious about tramadol. But there are probably better ways than upscheduling to reduce risks and improve outcomes. As a result, Public Citizen's petition seems quite narrow and unlikely to help with the overdose crisis.

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

This column is for informational purposes only and represents the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.

Experts Warn Rx Opioids Being Denied to Breast Cancer Patients

By Pat Anson, PNN Editor

Patients with advanced breast cancer are being denied opioid pain medication due to lack of supply in poor countries and a backlash against opioid addiction in the United States, according to experts at an international conference on breast cancer recently held in Lisbon.

In a session agreeing to new guidelines for treating breast cancer, oncology experts at the Advanced Breast Cancer Fifth International Consensus Conference also called for better access to a group of anti-cancer drugs called CDK4/6 inhibitors. The drugs help breast cancer patients live longer and improve their quality of life, but are often not available.  

The guidelines also warn that cancer patients should not have limits placed on their access to adequate pain control.

“Patients with advanced breast cancer can suffer pain and other symptoms, particularly towards the end of their lives. We need to ensure that appropriate pain medications and other symptom interventions are available to them,” said conference co-chair Eric Winer, MD, Director of Breast Cancer Program at Dana-Farber/Harvard Cancer Center in Boston.

“We acknowledge that the misuse of opioids is a big problem, particularly in the United States, but we need to make sure that in trying to deal with this problem we do not interfere with pain management in cancer patients. In addition, in some low- and middle-income countries, such as some in Africa, there are problems with patients being able to access any form of pain relief, and this needs to be addressed urgently.”

The panel of experts also called for more research into the use of cannabis for managing pain and other symptoms in patients with advanced breast cancer. But they cautioned that cannabis should not replace pain relievers that have been proven to work.

“The panel encourages research on the potential role of cannabis to assist in pain and symptom control but strongly stresses that it cannot replace proven medicines, such as morphine, for adequate pain control,” the guideline state.

Over two million new cases of breast cancer are diagnosed worldwide ever year, and there are about 600,000 deaths annually from the disease.

Confusion Over CDC Guideline

Although the CDC’s 2016 opioid guideline is only intended for primary care physicians treating non-cancer pain, the recommendations include patients “who have completed cancer treatment, are in clinical remission, and are under cancer surveillance only.”  

Experts say the CDC’s inclusion of cancer survivors is a mistake because it is not uncommon for cancer pain to persist long after the cancer is treated.  The CDC’s recommendations also conflict with cancer treatment guidelines that suggest doctors use both short and long-acting opioids when treating flares from cancer pain. The CDC recommends against long-acting opioids because of the potential risk of addiction.

The conflicting recommendations have caused confusion for oncologists and pharmacists, and agony for cancer patients not getting proper pain relief.

Earlier this year, a Rite Aid pharmacist refused to fill an opioid prescription for a California woman with Stage 4 terminal breast cancer.  April Doyle posted a tearful video online about her experience at the pharmacy that went viral. The pharmacist and a Rite Aid manager later apologized to Doyle for the incident.  

Rx Drug Databases Linked to Heroin Deaths

By Pat Anson, PNN Editor

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

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

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

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

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

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

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

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

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

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

DEA Sues Colorado for Access to PDMP

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

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

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

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

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

Patients on Rx Opioids Often Tapered at Risky Levels

By Pat Anson, PNN Editor

Tens of thousands of pain patients on long term opioid therapy have been cutoff or tapered to lower doses more rapidly than recommended, putting them at risk of withdrawal, uncontrolled pain and suicide, according to a large new study.

The study, published in JAMA Network Open, is one of the first to assess the impact of the 2016 CDC opioid guideline and other measures aimed at reducing opioid prescribing.

Researchers at University of California Davis reviewed the prescription records of over 100,000 patients on stable opioid doses from 2008 to 2017.

The percentage of patients who were tapered rose significantly during the study period -- from 10.5% in 2008 to 22.4% in 2017 – especially for patients on relatively high daily doses that exceeded 90 MME (morphine milligram equivalent).

“Opioid tapering has become increasingly common among patients using long-term opioids, particularly among patients taking higher doses and since the publication of the CDC opioid prescribing guideline,” researchers found.   

SOURCE: JAMA NETWORK OPEN

“Our results also suggest that many patients undergo tapering at rapid maximum rates. The downstream effects of opioid tapering on pain, withdrawal, mental health, and overdose risk warrant careful evaluation.”

Federal guidelines recommend a gradual dose reduction of about 10% per month. But researchers found that tapering for nearly one in five patients exceeded that level and some were tapered at rates six times higher than recommended. The average dose reduction overall was 27.6% per month.

"Tapering plans should be based on the needs and histories of each patient and adjusted as needed to avoid adverse outcomes," said study author Alicia Agnoli, MD, an assistant professor of family and community medicine at UC Davis. “Unfortunately, a lot of tapering occurs due to policy pressures and a rush to get doses below a specific and sometimes arbitrary threshold. That approach can be detrimental in the long run."

Too rapid tapering can have devastating consequences on patients and their families. Such was the case for Bryan Spece, a 54-year old Montana man who committed suicide after his dose of oxycodone was abruptly reduced by 70 percent. The pain clinic that tapered Spece said it was following the CDC guideline.

"He was the last person anyone would have thought to take his own life. He was just not that guy," a family member told PNN. "I know he was in a lot of pain and in a very dark spot."

Women More Likely to Be Tapered

Although men are twice as likely as women to die from an opioid overdose, UC Davis researchers found that tapering rates for women were about 13% higher than men, which they attribute to a possible sex bias.

“When considering dose tapering for patients, clinicians may fear that a recommendation of tapering may prompt angry or even violent responses, particularly from male patients. Such perceptions may be associated with a sex bias among clinicians, manifesting as a greater willingness to initiate tapering among women than men,” researchers said.

Although patients who survive an opioid overdose are at substantial risk of overdosing again, the study found that less than one in four patients (23.4%) with recent overdoses were tapered by their prescribers.

Researchers hope to build on the study further to develop best practices for dose reduction.

"Ultimately, we want to clarify the effects of tapering on patients and how to help them taper to maximize benefits and minimize risks," said lead author Joshua Fenton, MD, a professor of family and community medicine at UC Davis. "We expect this line of research will have important implications for how physicians manage and monitor patients who are undergoing opioid tapering."

The Food and Drug Administration first warned in April that many pain patients were being tapered inappropriately, putting them at risk of serious harm. That was followed a few days later by a pledge from CDC Director Robert Redfield, MD, to evaluate the impact of the agency’s opioid guideline and to “clarify its recommendations.”

Seven months later, not a single word of the CDC guideline has been changed or clarified. Outside of an editorial published in the New England Journal of Medicine, the CDC has made no effort to publicize or widely disseminate warnings to doctors not to taper patients too rapidly.

Not until last month – three and a half years after the CDC guideline was released – did the Department of Health and Human Services publish a 6-page guide for doctors on how to taper patients. The guide encourages prescribers to collaborate with patients and “obtain patient buy-in” before starting a tapering program.