Lyrica Not Effective for Treating Traumatic Nerve Pain

By Pat Anson, Editor

Pregabalin is not effective in relieving chronic pain caused by traumatic nerve injury, but it may be useful as an analgesic in treating pain after surgery, according to a new study published in the Journal of Neurology.

The placebo-controlled study followed 539 patients in North America, Europe, Africa and Asia for three months. About half had nerve pain after surgery, while the rest had nerve pain after an accident or trauma.

Researchers found that pregabalin was not an effective pain reliever for the patients with traumatic nerve injuries, but the drug did provide better pain relief than placebo for the surgery patients.

"While these finding show that pregabalin is not effective in controlling the long-term pain for traumatic injury, it may provide relief for patients (that) experience post-surgical pain," said lead author John Markman, MD, director of the Translational Pain Research Program in the University of Rochester Department of Neurosurgery.

"The possibility that there was pain relief for those patients who had a hernia repair, or breast surgery for cancer, or a joint replacement lays the groundwork for future studies in these post-surgical syndromes where there is so much need for non-opioid treatments."

Pregabalin, which is sold by Pfizer under the brand name Lyrica, is FDA-approved for the treatment of chronic pain associated with shingles, spinal cord injury, fibromyalgia, and diabetic peripheral neuropathy.

It is also commonly prescribed as an "off label" treatment for other types of chronic pain and as an alternative to opioid medication.

A major challenge for doctors is that biological changes in nerves and other tissues while healing from surgery or trauma vary from one patient to the next. There is also no diagnostic method that allows doctors to identify which patients will respond to a particular type of pain treatment.

"Given the rising rates of surgery and shrinking reliance on opioids, it is critical that we understand how to study new drugs that work differently in patients like the ones included in this study," Markman added.

While critics often say there is little or no evidence to support the long-term use of opioids, the same is true for other types of pain medication, including pregabalin. Nevertheless, in its guideline for opioids, the Centers for Disease Control and Prevention recommends pregabalin and its chemical cousin gabapentin as alternatives for treating chronic pain – without even mentioning their side effects or potential for abuse.

Pregabalin and gabapentin belong to a class of nerve medication called gabapentinoids, which were originally developed to treat epilepsy, not pain. In recent, deaths involving gabapentinoids have increased in the UK, Australia and Canada, where some addicts have learned the drugs can heighten the euphoric effect of heroin and other opioids.

The use of pregabalin and gabapentin has tripled in the U.S. over the past decade, but health officials have only recently started looking into their misuse and abuse. While gabapentin has a warning label cautioning users who take the drug with opioids, there is no similar warning for pregabalin.

Overdose Crisis Began 40 Years Ago

By Pat Anson, PNN Editor

The overdose crisis in the United States began long before a spike in opioid prescribing and is likely to last for many more years, according to a new study published in Science magazine.

Researchers at the University of Pittsburgh Graduate School of Public Health looked at nearly 600,000 poisoning deaths in the U.S. from 1979 to 2016 and found a steadily rising number of overdoses caused by “subepidemics” of different drugs, including heroin, cocaine, illicit fentanyl, methamphetamine and prescription opioids. As each subepidemic rose and fell, the drug fueling it was replaced by another substance that can be abused.

“The epidemic of drug overdoses in the United States has been inexorably tracking along an exponential growth curve since at least 1979, well before the surge in opioid prescribing in the mid-1990s,” said senior author Donald Burke, MD, Pitt Public Health dean and UPMC-Jonas Salk Chair of Global Health. 

“Although there have been transient periods of minor acceleration or deceleration, the overall drug overdose mortality rate has regularly returned to the exponential growth curve. This historical pattern of predictable growth for at least 38 years strongly suggests that the epidemic will continue along this path for several more years.”

Burke and his colleagues say the type of drug and the demographics of those who die from overdoses has fluctuated over the years. When the use of one drug waned, another drug replaced it, attracting new populations from different geographic regions.

When plotted on a map, certain drugs dominate different areas. Almost every region in the country is a hot spot for overdose deaths from one or more drugs. Heroin and cocaine primarily impact urban populations, while prescription opioids and methamphetamine skew a bit more rural. Cocaine increased death rates for black men, while heroin raised the death rates for younger whites and older blacks.

To be successful, researchers say overdose prevention efforts must extend beyond control of individual drugs. The current subepidemic of drug deaths caused by illegal and legal opioids will likely to be replaced by something else.

“The recent historical variability with which some specific drugs have waxed and waned makes predictions about the future role of specific drugs far more uncertain. Indeed, it is possible that in the future, the drug overdose epidemic may be driven by a new or heretofore obscure psychoactive substance,” Burke warned. 

Click on the video below to see a chart of the different subepidemics and how they align to form an exponential growth curve:

Technological factors fueling the epidemic include enhanced communication methods (smartphones and the Internet), faster supply chains (FedEx and UPS) and underground drug manufacturing that increased the supply of drugs while lowering their cost. Socioeconomic factors such as unemployment, lost social connections and lack of healthcare may also be creating a climate of despair that leads to drug abuse. 

“Understanding the forces that are holding multiple subepidemics together into a smooth exponential trajectory may be important in revealing the root causes of the epidemic, and thisunderstanding may be crucial to implementation of prevention and intervention strategies,” Burke said. 

“Evidence-based public health responses have contained past epidemics. If we understand and address these root causes at the same time that we take on the opioid crisis, we should be able to curb the epidemic for good."

‘Don’t Punish Pain’ Rallies Draw Local Media Coverage

By Pat Anson, PNN Editor

Hundreds of people – including some in wheelchairs and others on crutches – took part in a nationwide series of rallies Tuesday protesting the poor treatment of chronic pain patients.

“Don’t Punish Pain” rallies were held in over 80 cities from Anchorage, Alaska to Jacksonville, Florida. The protests were organized on Facebook by a grassroots group of pain patients, including many who have lost access to opioid medication or seen their doses drastically reduced due to federal and state guidelines that target opioid prescribing.   

Rally organizers were disappointed by the low turnout in some cities. Only a handful of people showed up for rallies in Las Vegas and Providence, Rhode Island. But over a hundred patients and their supporters rallied in Oklahoma City. And about two dozen people rallied on the steps of the state capitol in Olympia, Washington.

Due to their small size, the rallies have yet to attract the national media attention that organizers are hoping for.

But they have been successful in drawing local media coverage and getting reporters to tell a side of the “opioid crisis” that’s rarely addressed.

DON’T PUNISH PAIN RALLY IN OLYMPIA, WASHINGTON

“We’re invisible. We’re hidden in our homes and our beds and in our rooms,” Crystal Irwin told CBS4 News at a rally in Denver. “People don’t know what we’re going through.”

Ben Lawrence has lived with chronic pain since an accident in 2009. He told CBS4 he was still able to work until his doctors stopped giving him opioids.

“They make you feel like you’re a drug addict,” Lawrence said. “They don’t give me the medication I need to go to work. I want to go to work.”

Rally organizers in Stuart, Florida told ABC25 News that patients are being unfairly targeted in the opioid crisis when the real problem is illicit drugs.

"They are calling this an opioid crisis when actually it's a fentanyl crisis, and they can't control the drugs coming into the United States. But they can control people like us who get our pain medication to survive," said Michael Courtright.

Patients are calling for major changes in guidelines released by the CDC in 2016, which discourage doctors from prescribing opioids for chronic pain. Although voluntary and only intended for primary care physicians, the guidelines have been widely adopted as mandatory by insurers, regulators and healthcare providers.

“Chronic pain patients all across the country are losing access to their pain medications that they depended on sometimes for 20 or 30 years,” Kristen Blanton told Fox55 News in Urbana, Illinois.

Don’t Punish Pain organizers held their first nationwide rallies in April and are planning another series of protests in January.

FDA Expands Safe Prescribing Program for Opioids

By Pat Anson, PNN Editor

The U.S. Food and Drug Administration will require that educational training in pain management and safe opioid prescribing be offered to all healthcare providers under a major expansion of the agency’s Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS) program.

REMS is also being expanded to include immediate-release (IR) opioids such as hydrocodone, oxycodone and morphine. Until now, REMS regulations only applied to extended-release and long-acting (ER/LA) opioid analgesics, such as OxyContin and Exalgo. Warning labels will be updated for all IR opioids, which account for about 90 percent of opioid pain medications.

“Many people who become addicted to opioids will have their first exposure in the medical setting,” said FDA Commissioner Scott Gottlieb, MD, in a statement. “Today’s action, importantly, subjects immediate-release opioids – which are the most commonly prescribed opioid products – to a more stringent set of requirements.”

The REMS program was first established in 2012. It required manufacturers of ER/LA opioids to pay for continuing education programs for prescribers only. Updated educational content must now also be provided to nurses, pharmacists and other healthcare providers who seek it. The training will cover broader information about pain management, including alternatives to opioids for the treatment of pain.

The training is not mandatory, but the FDA is considering whether to require continuing educational programs in pain management and safe prescribing.

“The agency believes that all health care providers involved in the management of patients with pain should be educated about the safe use of opioids so that when they write or dispense a prescription for an opioid analgesic, or monitor patients receiving these medications, they can help ensure the proper product is selected for the patient and used with appropriate clinical oversight,” the agency said.

“I think these changes to the REMS are very good and long overdue,” said Bob Twillman, PhD, Executive Director of the Academy of Integrative Pain Management. “We know that the IR opioids are much more highly sought-after, versus ER/LA opioids, for purposes of abuse, and there is absolutely no reason why they (and their manufacturers) should be exempt from this requirement.  

“I’m not concerned, at this stage, about this change causing primary care providers to back off on prescribing, given that participation in the program is still completely voluntary for healthcare providers. If this voluntary status changes, and FDA finds a way to make REMS education mandatory, I will be concerned that some providers will opt out of prescribing opioids altogether.”

The FDA’s action greatly expands the number of opioid products covered by REMS from 62 to 347 opioid analgesics. The updated warning labels will strongly encourage providers to complete a REMS education program, and to counsel patients and caregivers on the safe use of opioid medication.

“Our goal is to help prevent patients from becoming addicted by decreasing unnecessary or inappropriate exposure to opioids and fostering rational prescribing to enable appropriate access to those patients who have legitimate medical need for these medicines,” said Gottlieb.

Opioid prescriptions in the United States fell sharply during the first half of 2018 and now stand at their lowest levels since 2003, according to data released last month by the FDA. The trend appears to be accelerating as many doctors lower doses, write fewer prescriptions or simply discharge pain patients.

While opioid prescriptions decline, overdoses continue to rise. According to preliminary data from the CDC, nearly 49,000 Americans died from opioid overdoses in 2017, over half of them due to illicit fentanyl, heroin and counterfeit drugs, not prescription opioids.

Former Tennant Patients Get New Doctor

By Pat Anson, PNN Editor

At a time when many pain patients have difficulty finding doctors willing to treat them, some of the sickest and most complicated pain patients in the U.S. have found a new physician. Or to be more precise, she found them.

Dr. Margaret Aranda is treating former patients of Dr. Forest Tennant, a prominent California pain physician who recently retired from clinical practice.  Tennant was seeing about 150 patients with severe intractable pain at his West Covina pain clinic. Most suffer from arachnoiditis, a chronic and painful disease of the spinal cord, and traveled to California from out-of-state because they could not find effective treatment locally.

Tennant, who is 77, is a beloved figure in the pain community. He was forced into retirement after the DEA raided his clinic last year and alleged he was running a pill mill. No charges were ever filed, but Tennant reluctantly agreed to close his clinic on the advice of his lawyer and doctor. That’s when Aranda stepped in and offered to take on Tennant’s patients.

“I feel very happy to be here and to be doing this and to feel qualified to do it because of my experience, my background and my education. But I think the thing I love the most is the connection I have with patients who understand that I’ve been through a lot myself,” said Aranda, an anesthesiologist whose medical career was put on hold for several years while she recovered from a car accident that left her with traumatic brain injuries.

“They just seem be relieved that they can talk to somebody who knows what it feels like. I think Dr. Tennant did that for them too. He wasn’t sick like a lot us were sick, but he carried that empathy with him. I find this to be very spiritual. I feel like I’m in the right place at the right time in my life and everything I went through prepared me for this.”

DR. MARGARET ARANDA

Tennant had success treating patients with an unusual combination of high dose opioid prescriptions, hormones, anti-inflammatory drugs and other medications, which Aranda plans to continue.

“I’m working to decrease the opioids as much as possible. For some patients that’s totally impossible, for others it’s not,” she told PNN. “I really think what we’re doing is redefining palliative care. I tell people this isn’t a pain clinic. This is a ‘keep you out of a wheelchair’ clinic. Keep you in the family. Keep you getting out of your house here and there.”

“Dr. Aranda is very intelligent and picked up on the scientific precepts of this disease and other things very rapidly,” says Tennant. “I was tickled to death the way she’s caught on to all this and knows how to carry on everything I was doing. Plus, she’s improving a lot of things I was doing.”

Under a Microscope

Aranda admits being a little worried about being scrutinized by the DEA.

“Of course, that would be the natural inclination I think for anyone in my field. It’s a little bit scary to walk in the shoes of a man who is so well known and beloved by everyone and had issues with the DEA I think most people felt were unfounded,” Aranda said.

“I am of course very concerned that they could be looking at me with a microscope. Or a double and triple microscope. But I think they already know our patient population and they now understand that we do have some of the sickest patients in the country. That’s why they come to us from all over. And so, we’re just careful.”

While Tennant operated his clinic basically as a charity, Aranda is “cash only” and will not accept medical insurance.  She is temporarily seeing patients at a clinic in Malibu but is looking for a permanent location.

Like Tennant, Aranda is willing to treat patients from out-of-state, including those who suffer from severe intractable pain. Patients interested in seeing Aranda can reach her at (800) 992-9280.   

DR. FOREST TENNANT

As for Tennant, he’s not quite ready to retire completely. He plans to continue researching arachnoiditis, a progressive and incurable disease that often begins when the spinal cord is damaged during surgery or punctured by a misplaced needle during an epidural steroid injection.

Inflammation sets in and can spiral out of control, forming scar tissue that cause spinal nerves to stick together. That leads to adhesive arachnoiditis and neurological problems, which can cause burning or stinging pain that can be felt from head to toe.

Arachnoiditis is poorly understood and often misdiagnosed as “failed back syndrome.” Tennant estimates as many as a million Americans may have it. Few doctors are trained to recognize the symptoms or know how to treat it.

“I’m going to be spending my time trying to research and educate on arachanoiditis. I think it’s the biggest, most severe pain problem we have,” says Tennant. “Before I hang up my spurs totally I want to make sure arachnoiditis is known to every family doctor and nurse practitioner in every community in the country.”

The Role of Suicide in the Opioid Crisis

By Roger Chriss, PNN Columnist

Suicide is an under-appreciated factor in the opioid crisis. Media reports rarely mention it, and pundits and politicians often ignore it. But the reality emerging from experts and a careful study of drug deaths shows that it is very important.

“We’ve done preliminary work suggesting that 22 to 37 percent of opioid-related overdoses are, in fact, suicides or suicide attempts,” Bobbi Jo Yarborough, PsyD, an investigator at the Kaiser Permanente Center for Health Research, told HealthItAnalytics.

Yarborough’s estimate is 2 to 3 times higher than the CDC’s. The CDC’s Annual Surveillance Report of Drug-Related Risks and Outcomes states that there were 5,206 suicides among the 47,105 poisoning deaths in 2015. This represents a suicide rate of 11 percent. The CDC gives similar data for 2016 drug deaths, estimating that only 8% were suicides.

Recognition of the importance of suicide in the opioid crisis has been slow to come.

In 2017, then-president of the American Psychiatric Association, Dr. Maria Oquendo, suggested that the suicide rate may be as high as 40 percent, writing in a guest blog for the National Institute on Drug Abuse (NIDA) that the risk for suicide death was over 2-fold for men with opioid use disorder and for women it was more than 8-fold.

Now, finally, interest in this issue is growing. The American Foundation for Suicide Prevention recently issued its first grant for studying suicide related to opioid use.

Kaiser Permanente also recently received a grant from NIDA to “examine the role of opioid use in suicide risk and develop better tools to help clinicians identify patients who are at highest risk.”  Kaiser researchers plan to use machine learning and analytics to predict the likelihood of a suicide attempt within 90 days of a primary care outpatient or mental health visit.

Fundamental questions about suicide in the opioid crisis remain to be answered.

"No one has answered the chicken and egg (question)," Dr. Kiame Mahaniah, a Massachusetts family physician, told NPR. “(Do people) have mental health issues that lead to addiction, or did a life of addiction then trigger mental health problems?”

Similarly, people with chronic pain disorders are thought to be “at increased risk for suicide compared with the general population,” as noted in a 2018 PAINWeek conference presentation.

But causality is also uncertain. At present it is not clear what proportion of suicides in the opioid crisis are due to despair, anxiety, addiction or the increasingly poor quality of pain care. There are many anecdotal reports of pain patient suicides, a tragically ignored feature of the crisis.

These distinctions are critical for public health policy in the opioid crisis. Current policy is largely geared toward restricting the opioid supply and monitoring legal pills after prescription. This does little to address underlying mental health issues, illegal drug use, or the impact of psychosocial or economic circumstances on people.

We need a clearer understanding of the opioid crisis, and that includes suicide.

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.

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It 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.

Widely Used Painkiller Raises Risk of Heart Problems

By Pat Anson, Editor

The most widely used painkiller in the world should be banned as an over-the-counter drug because it significantly raises the risk of cardiovascular problems and gastrointestinal bleeding, according to a large new study published in the British Medical Journal (BMJ).

Diclofenac is not well-known in the United States, but it is the most widely used non-steroidal anti-inflammatory drug (NSAID) in the world. It is sold both as a prescription and over-the-counter medication under various brand names such as Voltaren, Cambia, Zorvolex and Solaraze.

Researchers looked at healthcare data from over 6 million people in Denmark from 1996 to 2016 and found that those who used diclofenac were 50 percent more likely to have cardiovascular problems such as atrial fibrillation, heart failure and stroke in the first 30 days compared to those who took nothing. Their risk of gastrointestinal bleeding was also higher.

Out of every 1,000 people who used diclofenac, the study estimated that four additional people would develop a major health problem within a year.

"It is time to acknowledge the potential health risk of diclofenac and to reduce its use. Diclofenac should not be available over the counter, and when prescribed, should be accompanied by an appropriate front package warning about its potential risks," wrote lead author Morten Schmidt, MD, Aarhus University Hospital.

"Treatment of pain and inflammation with NSAIDs may be worthwhile for some patients to improve quality of life despite potential side effects. Considering its cardiovascular and gastrointestinal risks, however, there is little justification to initiate diclofenac treatment before other traditional NSAIDs."

This is not the first time that researchers have warned about the health risks associated with diclofenac and other NSAIDs.

In 2016, researchers at 14 European universities and hospitals, including a number of leading heart specialists, warned that some NSAID’s raise cardiovascular risk and that there is no "solid evidence" the drugs are safe.

Some of the greatest cardiovascular risk comes from a class of NSAIDs known as COX-2 inhibitors. A COX-2 inhibitor called Vioxx was voluntarily pulled from the market by Merck in 2004, but many other COX-2 inhibitors, such as diclofenac, are still widely used for pain relief.   

Another 2016 study published in the BMJ found that use of any NSAID was associated with a 20 percent higher risk of being hospitalized with heart failure. These seven NSAIDs were found to be the riskiest:

• diclofenac
• ibuprofen
• indomethacin
• ketorolac
• naproxen
• nimesulide
• piroxicam

NSAIDs are used to alleviate pain and reduce inflammation, and are found in a wide variety of over-the-counter products – from headache relievers to cold and flu remedies. They are used in so many different products -- such as Advil and Motrin -- that many consumers may not be aware how often they use NSAIDs. 

In 2015, the U.S. Food and Drug Administration ordered warning labels for all NSAIDs to be strengthened to indicate they increase the risk of a fatal heart attack or stroke. The FDA said studies found the risk of serious side effects can occur in the first few weeks of using NSAIDs and could increase the longer people use the drugs. The revised warning does not apply to aspirin.

The European Society of Cardiology recommends limited use of NSAIDs by patients who are at increased risk of heart failure. Those already diagnosed with heart failure should refrain from using NSAIDs completely.

Oregon Health Official Defends Opioid Plan

By Pat Anson, Editor

The head of Oregon’s Health Authority is defending a controversial plan that would force many of the state’s Medicaid patients off opioids.

In an op/ed this week in the Wall Street Journal, Patrick Allen wrote that patients deserve “safe, effective choices to relieve pain -- not just a pill.” He suggested physical therapy, exercise and massage would be better alternatives.

At issue is a task force recommendation to limit Medicaid coverage of opioids to just 90-days for five broad chronic pain conditions – including fibromyalgia and chronic pain caused by trauma.  Patients already on opioids longer than 90 days would be given one year to taper off the medications and switch to alternative therapies that would be covered by Medicaid.

The plan has drawn criticism nationwide from chronic pain patients, advocates and pain management experts. Drs. Sally Satel and Stefan Kertesz wrote in another WSJ op/ed that the plan would “exacerbate suffering for thousands of patients.”

Allen disagrees, saying opioids are too risky to use long-term.

“This new proposal would expand evidence-based options for chronic pain management, allowing Oregonians to find a care plan that works for them,” Allen wrote.  “Evidence is insufficient to determine the effectiveness of long-term opioid therapy for improving chronic pain and function.

“Offering only one pain-management option that continues to kill Americans at alarming rates is a tragedy we can’t accept.”

According to his LinkedIn profile, Allen does not hold a medical degree and has spent most of his career working in the banking industry and as a state regulator in consumer and business affiars. He was appointed last year as director of the Oregon Health Authority, which operates the state’s Medicaid program and purchases health insurance for over 400,000 public employees and teachers.

PATRICK ALLEN

Oregon’s Health Evidence Review Commission held a public hearing on the opioid proposal earlier this month, but has not given final approval. If adopted, the opioid restrictions would not go into effect until 2020.

Opioid prescribing in Oregon has been declining for years – as it has nationwide – but the state has the highest rate of non-medical use of prescription opioids in the country. About three Oregonians die every week from an opioid overdose.

CDC: Most Overdoses Involve Illicit Opioids

By Pat Anson, Editor

The Centers for Disease Control and Prevention has released a new report further documenting the changing nature of the opioid crisis and the lesser role played by opioid pain medication in drug overdoses.

The report from the CDC’s Enhanced State Opioid Overdose Surveillance (ESOOS) program looked at nearly 12,000 opioid overdose deaths in 11 states from July 2016 to June 2017. 

Nearly 59 percent of the overdose deaths were attributed to illicit opioids like fentanyl and heroin, while 18.5% had both illicit and prescription opioids.

Less than 18% tested positive for prescription opioids only.

Many of the deaths involved someone with a criminal record or a history of substance abuse. Nearly one in ten overdose victims had been released from a prison or jail in the month preceding the overdose.

Evidence of injection drug use was found in about half of the illicit opioid deaths and about 15% had lived through a previous overdose.

OPIOID OVERDOSES (2016-2017)

Source: CDC Enhanced State Opioid Overdose Surveillance

There were also distinct differences in demographics between the illicit and prescription opioid overdoses. The average age of people who died from prescription opioids was 47, while the average age of those who died from illicit opioids was 36. Men were far more likely to overdose on an illicit opioid (73%), while more women (51%) died from a prescription opioid overdose.

“Findings from this analysis indicate that illicit opioids were a major driver of opioid deaths, especially among younger persons, and were detected in approximately three of four deaths overall. Prescription opioids were detected in approximately four of 10 deaths,” CDC researchers reported in the Morbidity and Mortality Weekly Report (MMWR).

Polysubstance Overdoses

Another key finding from the report was the frequent involvement of other drugs in opioid overdoses.

Benzodiazepines – a class of anti-anxiety medication that includes Xanax and Valium – were detected in over half of the prescription opioid deaths and in about one of every four illicit opioid deaths. “Benzos” depress the central nervous system and raise the risk of overdose when used with opioids. 

Gabapentin (Neurontin) – an anti-seizure drug widely prescribed off-label to treat pain -- was detected in over 21% of the prescription opioid deaths and in about 10% of the other overdoses.

“The combined use of gabapentin and opioids might be an indicator of high-risk opioid misuse and requires further study,” researchers said. “Extensive use of cocaine and benzodiazepines among deaths where both prescription and illicit opioids were detected highlights the need for prevention and treatment programs to address polysubstance use.”

Because so many drugs – both legal and illegal -- are often involved in overdoses, the CDC researchers cautioned that efforts to prevent opioid abuse “should not focus exclusively on one opioid type.”

That warning is at odds with the CDC’s own Rx Awareness program, an advertising campaign launched last year that focuses solely on the stories of people “whose lives were torn apart by prescription opioids.”

Fentanyl, heroin and other drugs commonly involved in overdoses are not addressed by the Rx Awareness campaign. 

“Specificity is a best practice in communication, and the Rx Awareness campaign messaging focuses on the critical issue of prescription opioids. Given the broad target audience, focusing on prescription opioids avoids diluting the campaign messaging,” the CDC explained when launching the campaign.

RX AWARENESS AD

Earlier this year, CDC researchers acknowledged that they overestimated the number of overdoses involving prescription opioids by combining them with deaths attributed to illicit fentanyl and other synthetic opioids. The ESOOS program was launched, in part, to correct that error.

ESOOS data is considered more reliable because it includes blood toxicology reports, as well as death certificates, medical examiner and coroner reports, death scene investigations, and an overdose victim’s history of substance abuse. A total of 32 states participate in ESOOS.

The 11 states participating in the current report include: Oklahoma, New Mexico, Maine, Massachusetts, New Hampshire, Rhode Island, Missouri, Ohio, West Virginia, Wisconsin and Kentucky.

Opioid Prescriptions Plunge to 15-Year Low

By Pat Anson, Editor

The volume of opioid prescriptions in the United States has fallen sharply and now stand at their lowest levels since 2003, according to data released by the Food and Drug Administration.

Over 74 million metric tons of opioid analgesics were dispensed in the first six months of 2018, down more than 16 percent from the first half of 2017. Opioid prescriptions have been declining for several years, but the trend appears to be accelerating as many doctors lower doses, write fewer prescriptions or simply discharge pain patients.

“These trends seem to suggest that the policy efforts that we’ve taken are working as providers, payers and patients are collectively reducing some of their use of prescription opioid analgesic drugs,” said FDA commissioner Scott Gottlieb, MD, in a statement.

SOURCE: FDA AND IQVIA

"This graph confirms the perception that many of use have, that prescribing continues to decline," said Bob Twillman, PhD, Executive Director of Academy of Integrative Pain Management. "But, the question remains --what is the effect of this decreased prescribing on people with chronic pain?

"Measures of prescribing need to be matched with measures of patient function and quality of life, especially given evidence that decreased prescribing may actually be associated with increased suicide. All this measure really tells us is that the intense pressure from legislators, regulators, and payers has had its desired effect of driving down prescribing, even it there’s no evidence that it’s done anything else helpful."

While opioid prescriptions decline, overdoses continue to rise. According to preliminary data from the CDC, nearly 49,000 Americans died from opioid overdoses in 2017, over half of them due to illicit fentanyl and heroin, not prescription opioids.

“It isn’t necessarily the case that more people are suddenly switching from prescription opioids to these illicit drugs. The idea of people switching to illicit drugs isn’t new as an addiction expands, and some people have a harder time maintaining a supply of prescription drugs from doctors,” said Gottlieb. “What’s new is that more people are now switching to highly potent drugs that are far deadlier. That’s driven largely by the growing availability of the illicit fentanyls.”

Illicit fentanyl and its chemical cousins are synthetic opioids, 50 to 100 times more potent than morphine. They are produced largely by clandestine drug labs in China and then smuggled into the U.S., where they are often mixed with heroin, cocaine and counterfeit drugs.  A record 1,640 pounds of fentanyl and nearly 5,500 pounds of heroin have been seized by law enforcement so far this year; likely a small fraction of what’s available on the black market.

While the Trump administration has expanded efforts to stop the distribution and sale of illicit opioids, it also remains focused on reducing the supply of prescription opioids.  The FDA plans to develop new prescribing guidelines for treating short-term, acute pain that will likely set a cap on the number of pills that can be prescribed for certain medical conditions.

“No more 30-day prescriptions for a tooth extraction or an appendectomy,” said Gottlieb.

The Justice Department also recently announced plans to lower production quotas by 10% next year for six widely prescribed opioid medications. The goal of the administration is to reduce opioid prescriptions by a third in the next three years. 

“The number of opioid prescriptions is only one of many factors and may not be the most important factor contributing to the opioid crisis. In fact, the U.S. is at a 15-year low in the amount of opioid prescribed but continues to see a surge of drug overdoses,” said Lynn Webster, MD, a pain management expert and past president of the American Academy of Pain Medicine.

“Much of the effort to curb the amount of prescription opioids has contributed to more suffering by people in chronic pain and possibly the increase in suicides.  It also hasn't done anything to curb the number of overdose deaths. Rather than being focused on number of pills or amount of opioid prescribed we need to focus on what is the best and most appropriate treatment for individual patients. When that is done properly, the right amount of opioids will be prescribed.”  

90% of Massachusetts Overdoses Linked to Fentanyl

By Pat Anson, Editor

Nearly 90 percent of opioid-related overdose deaths in Massachusetts now involve fentanyl, according to a new report that documents the rapidly changing nature of the opioid crisis. Less than 20 percent of drug overdoses in the state were linked to prescription opioids.

In the second quarter of 2018, Massachusetts health officials say 498 people died from an opioid-related overdose – the third straight quarter that opioid deaths have declined.

But the good news was tempered by the rising toll taken by fentanyl -- the synthetic opioid that’s become a deadly scourge on the black market. Fentanyl is often mixed with heroin, cocaine and counterfeit drugs to increase their potency. 

Because Massachusetts was one of the first states to conduct blood toxicology tests in overdose cases, it’s quarterly reports on drug deaths are considered more accurate than federal estimates and more likely to spot emerging trends in drug use. 

"This quarterly report provides a new level of data revealing an unsettling correlation between high levels of synthetic fentanyl present in toxicology reports and overdose death rates. It is critically important that the Commonwealth understand and study this information so we can better respond to this disease and help more people,” Massachusetts Gov. Charlie Baker said in a statement.

Another trend documented in Massachusetts is the increasing role played by cocaine and benzodiazepines --- an anti-anxiety medication – in drug overdoses. In the first quarter of 2018, cocaine (43%) and benzodiazepines (42%) were involved in more overdoses than heroin (34%) and prescription opioids (19%). 

SOURCE: MASSACHUSETTS DEPARTMENT OF PUBLIC HEALTH

Drug experts say many cocaine users may not realize their drug has been spiked with fentanyl, while many people who buy Xanax or Valium on the black market don’t know they’re getting counterfeit medication laced with fentanyl.

“If you are using illicit drugs in Massachusetts, you really have to be aware that fentanyl is a risk no matter which drug you’re using,” Dr. Monica Bharel, Massachusetts public health commissioner told The Boston Globe. “The increased risk of death related to fentanyl is what’s driving this epidemic.”

Fentanyl is also involved in a growing number of fatal overdoses in Pennsylvania. According to the Drug Enforcement Administration, there were 5,456 overdose deaths in Pennsylvania last year. Of those, over 67% percent involved fentanyl. The presence of fentanyl or its chemical cousins in overdose deaths rose almost 400% in the state from 2015 to 2017.

Most overdoses involve multiple drugs and blood tests alone do not determine a cause of death -- only which drugs were present at the time of death.

Former CDC Director Arrested for Sexual Misconduct

By Pat Anson, Editor

Dr. Thomas Frieden, the former director of the Centers for Disease Control of Prevention, has been arrested on sexual misconduct charges in New York City.

Frieden turned himself in to police in Brooklyn Friday morning after being charged with forcible touching, harassment and third degree sex abuse, all misdemeanors. The charges stem from a complaint filed in July by a 55-year old unnamed woman who alleges the 57-year old doctor grabbed her buttocks without permission in his apartment last October. 

According to STAT, Frieden later apologized to the woman -- a longtime family friend -- and "tried to manipulate her into staying silent by citing his position and potential to save lives around the world."

Fried was arraigned Friday afternoon and released without bail, after a judge ordered him not to contact his accuser and to surrender his passport. He's due back in court October 11.

Frieden did not enter a plea. A spokesperson released a statement saying the incident "does not reflect Dr. Frieden’s public or private behavior or his values over a lifetime of service to improve health around the world.”

Frieden led the CDC from 2009 to 2017 and championed the agency’s controversial opioid prescribing guideline -- calling it an "excellent starting point" to prevent opioid abuse.

Although voluntary and only intended for primary care physicians, the guideline has been widely adopted by insurers, states and healthcare providers – resulting in many chronic pain patients losing access to opioid medication.

“This crisis was caused, in large part, by decades of prescribing too many opioids for too many conditions where they provide minimal benefit," Frieden wrote in a commentary published by Fox News.  “There are safer drugs and treatment approaches that can control pain as well or better than opioids for the vast majority of patients."

DR. THOMAS FRIEDEN

Frieden currently heads Resolve to Save Lives, a program of Vital Strategies, a non-profit health organization that is trying to improve public health worldwide.

Vital Strategies released a statement saying Frieden informed the organization in April about the misconduct allegation. His accuser does not work for Vital Strategies, but the organization hired an investigator to interview employees about Frieden. No inappropriate workplace behavior or harassment was found, according to Vital Strategies CEO Jose Castro.  

“I have known and worked closely with Dr. Frieden for nearly 30 years and have seen first-hand that he has the highest ethical standards both personally and professionally. Vital Strategies greatly values the work Dr. Frieden does to advance public health and he has my full confidence,” said Castro.

Frieden has an extensive background in epidemiology and infectious diseases, and his tenure at the CDC was marked by major efforts to combat the Ebola virus, fungal meningitis, influenza and the Zika virus.

Before his appointment as CDC director, Frieden was New York City’s health commissioner, where he led efforts to ban public smoking and remove unhealthy trans fats from restaurants. Frieden is married and has two children.

FDA to Develop Acute Pain Guidelines

By Pat Anson, Editor

The head of the U.S. Food and Drug Administration is following up on a promise to develop new federal prescribing guidelines for treating short-term, acute pain. But don't expect an overhaul of the CDC's controversial opioid guideline.

FDA commissioner Scott Gottlieb, MD, announced today that his agency has awarded a contract  to the National Academies of Sciences, Engineering, and Medicine (NASEM) to help develop guidelines for prescribing opioids for acute pain that results from specific medical conditions or procedures, such as wisdom tooth removal or post-operative pain.  

The CDC guideline takes a one-size-fits-all approach to chronic pain -- pain that lasts longer than three months -- and doesn't distinguish between pain from fibromyalgia, arthritis, neuropathy or any other medical condition.  

"We’ve contracted with NASEM to conduct a consensus study and issue a report on its findings. This work will begin with an identification and prioritization of procedures and conditions associated with acute pain for which opioid analgesics are commonly prescribed and where evidence-based clinical practice guidelines would help inform prescribing practices," Gottlieb said in a statement.

"We acknowledge the work of our colleagues at the U.S. Centers for Disease Control and Prevention (CDC) who have taken an initial step 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. The guidelines we generate would be distinct from this corresponding effort by the CDC, in that our effort would be indication-specific." 

Importantly, Gottlieb says NASEM will hold a series of public meetings and workshops, and seek input from "a broad range of stakeholders" from different medical specialties. The CDC guideline was initially developed with no public hearings and with little input from pain management experts.

While Gottlieb clearly wants more transparency brought to the guideline development process, he also clings to the notion that opioid medication is overprescribed and is primarily responsible for the nation's opioid crisis.

"Many people who become addicted to opioids will first be exposed to these drugs through a lawfully prescribed medication. Unfortunately, the fact remains that there are still too many prescriptions being written for opioids," Gottlieb said.

"Our analyses suggest that the first prescription for many common, acute indications could typically be for many fewer pills – maybe just a day or two of medication rather than a 30-day supply, which is typically prescribed. In some cases, the excess pills that aren’t used by patients may end up being diverted to illicit markets or misused or abused by friends or family members. In other cases, patients who are prescribed more medication than necessary may find themselves at increased risks for misuse, abuse and addiction."

But studies show that long-term opioid use by patients recovering from surgery is rare and less than one percent of legally prescribed opioids are diverted.

In 2016, the American Pain Society released guidelines that encourage physicians to limit the use of opioids and offer “multimodal therapies” to patients suffering from postoperative pain. Among the treatments suggested are pregabalin, gabapentin, NSAIDs and acetaminophen.

The University of Michigan has also developed prescribing guidelines for over a dozen common surgeries, ranging from hernia repair to hysterectomies. The recommendations list the suggested dose of opioids and number of pills for each procedure.      

Several states have already adopted their own guidelines for acute pain, limiting opioids to a few days' supply -- regardless of whether the pain is from a broken leg, a tonsillectomy or gunshot wound.  It's not clear how federal guidelines for acute pain would impact state regulations.

Studies Warn of Pregabalin Deaths

By Pat Anson, Editor

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

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

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

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

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

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

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

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

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

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

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

Pregabalin Abuse in Australia

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

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

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

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

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

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

Study Finds Racial Bias in Drug Testing

By Pat Anson, Editor

African-American patients on long-term opioid therapy are more likely to be drug tested by their doctors and significantly more likely to have their opioid prescriptions stopped if an illicit drug is detected, according to a new study.

Yale researchers analyzed the health records of more than 15,000 patients who received opioids from the Veterans Administration between 2000 and 2010. About half of the VA patients were white and half black.

Over 25 percent of the black patients had a urine drug test within the first six months of opioid treatment, compared to nearly 16% of whites.

When patients tested positive for either marijuana or cocaine, the vast majority – 90 percent -- continued to receive their opioid prescriptions. But there were significant differences in how patients were treated depending on their race.

Black patients that tested positive for marijuana were twice as likely as whites to have opioid therapy stopped and three times more likely to have opioids discontinued if cocaine was detected in their urine.

The findings, published in the journal Drug and Alcohol Dependence, are consistent with previous research showing disparities in how blacks and whites are treated by the healthcare system in general, and particularly when opioids are involved.

“There is no mandate to immediately stop a patient from taking prescription opioids if they test positive for illicit drugs,” said first author Julie Gaither, PhD, a pediatrics instructor at the Yale School of Medicine.

“It’s our feeling that without clear guidance, physicians are falling back on ingrained stereotypes, including racial stereotyping. When faced with evidence of illicit drug use, clinicians are more likely to discontinue opioids when a patient is black, even though research has shown that whites are the group at highest risk for overdose and death.”

A 2016 study of emergency room patients found that blacks were significantly less likely to get an opioid for abdominal pain than whites. Another study of white medical students and residents found that half had at least one false belief about black patients. Those that did were more likely to report lower pain ratings for black patients.

Drug Testing for Marijuana Not Recommended

The 2016 CDC opioid guideline encourages doctors to conduct urine drug tests before starting opioid therapy and at least annually after patients start taking the drugs. But the guideline also urges physicians not to test opioid patients for tetrahyrdocannabinol (THC), the psychoactive ingredient in marijuana that makes people high.

“Clinicians should not test for substances for which results would not affect patient management or for which implications for patient management are unclear. For example, experts noted that there might be uncertainty about the clinical implications of a positive urine drug test for tetrahyrdocannabinol (THC).” the guideline states.

"Clinicians should not dismiss patients from care based on a urine drug test result because this could constitute patient abandonment and could have adverse consequences for patient safety, potentially including the patient obtaining opioids from alternative sources and the clinician missing opportunities to facilitate treatment for substance use disorder."

Another factor to consider is the unreliability of urine drug tests. As PNN has reported, “point-of care” (POC) urine drug tests, the kind widely used in doctor’s offices, frequently giving false positive or false negative results for marijuana, cocaine and other drugs. 

A 2015 study found that 21% of POC tests for marijuana and 12% of those for cocaine produced a false positive result.