The CDC, Opioids and Cancer Pain

By Roger Chriss, PNN Columnist

In 2016, the Centers for Disease Control and Prevention issued its controversial opioid prescribing guideline. Insurers, states and other federal agencies soon followed with mandatory policies and regulations to reduce the use of opioid pain medication. All this was supposed to exclude cancer-related pain care, but in practice that’s not what happened.

Dr. Judith Paice, director of the Cancer Pain Program at Northwestern University’s Feinberg School of Medicine, told the National Cancer Institute in 2018 that the opioid crisis “has enhanced fear — fear of addiction in particular” among both patients and doctors.

“Many primary care doctors no longer prescribe opioids. Oncologists are still prescribing these medications, but in many cases they’re somewhat anxious about doing so. That has led some patients to have trouble even obtaining a prescription for pain medication,” Paice said.

In 2019, the Cancer Action Network said there has been “a significant increase in cancer patients and survivors being unable to access their opioid prescriptions.” One out of four said a pharmacy had refused to fill their opioid prescription and nearly a third reported their insurance refused to pay for their opioid medication.

That same year, CDC issued a long-awaited clarification noting the “misapplication” of the guideline to patients it was never intended for, including “patients with pain associated with cancer.”  

Long Term Use of Opioids Uncommon

Cancer pain management in the U.S. has been severely impacted by the CDC guideline, even though rates of long-term or “persistent” opioid use are relatively low and stable:

• A major review of over 100,000 military veterans who survived cancer found that only 8.3% were persistent opioid users. Less than 3% showed signs of opioid abuse or dependence.

• A study of older women with breast cancer who were prescribed opioids found that only 2.8% were persistent opioid users.  

• A study of 276 patients with head or neck cancer found that only 20 used opioids long-term – a rate of 7.2 percent.

• And a study of nearly 23,500 women with early-stage breast cancer who had a mastectomy or mastectomy found that 18% of them were using opioids 90 to 180 days after surgery, while 9% were still filling opioid prescriptions 181 to 365 days later.

While any sign of opioid abuse or addiction is concerning, these studies show that long-term use of opioid medication is relatively uncommon among cancer survivors. The American Cancer Society says opioids are “often a necessary part of a pain relief plan for cancer patients” and “can be safely prescribed and used” for cancer pain.

Cancer patients and their doctors have been successfully managing opioid risks long before the CDC guideline or associated state laws and regulations. Perhaps it is time for lawmakers, regulators, insurers and pharmacies to learn from the cancer community rather than getting in the way of clinical best practices.

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. 

Study: Using Cannabis for Pain Relief Reduces Risk of Opioid Overdose

By Pat Anson, PNN Editor

Illicit drug users who use cannabis for pain relief are less likely to experience an opioid overdose or use heroin, according to a Canadian study recently published in the online journal PLOS ONE.

Researchers at the University of British Columbia (UBC) the BC Centre on Substance Use (BCCSU) interviewed nearly 900 illicit drug users in Vancouver who reported using cannabis between 2016 and 2018. Participants were asked whether they used cannabis to relieve pain, improve sleep, address nausea or for recreation. Most said they used cannabis for a medically therapeutic reason.

"We're seeing more and more in our research that people are using cannabis for therapeutic reasons," says lead author Stephanie Lake, a doctoral candidate at UBC's School of Population and Public Health. "We're also seeing that, for some individuals in our study, this therapeutic use corresponds with either less use of illicit opioids or a reduced risk of overdose."

Participants who used cannabis for pain relief had lower odds of a non-fatal opioid overdose and for injecting heroin daily. Previous research from the BCCSU found that many people at risk of overdose, particularly those living with pain, may be using cannabis to reduce their reliance on illicit opioids.

Another key finding of the study was that therapeutic cannabis users relied on illicit sources for their cannabis supply – even though medical marijuana was fully legalized in Canada in 2013. About half of study participants said that illegal dispensaries were their most important source of cannabis.

"The mounting evidence related to the motivations behind people's cannabis use strongly suggests that improving access to cannabis for therapeutic purposes could help reduce overdose risk associated with illicit opioid use," says M.J. Milloy, PhD, a research scientist at BCCSU who was senior author of the study.

"Authorities should pause their efforts to close unregulated sources of cannabis and eliminate the illicit market until barriers to legal cannabis are addressed, especially during the overdose crisis."

Vancouver was the first major North American city to be hit by a wave of overdoses involving illicit fentanyl, heroin and other street drugs. A public health emergency was declared in British Columbia in 2016. Since then, Vancouver has become a laboratory of sorts for novel ways at addressing addiction, such as providing a “safe supply” of prescription opioids and prescription heroin to illicit drug users.

“Our community and many others across Canada and the United States are experiencing an opioid overdose crisis rooted, in part, in inadequately or inappropriately-managed chronic pain and sparked by widespread exposure to an unregulated illicit opioid supply contaminated with potent opioid analogues,” researchers concluded. “Our finding may also reflect an opioid-sparing effect of cannabis, whereby opioids are not replaced, but the dosage or frequency of opioid required for analgesia is reduced with the use of cannabis.”

Other studies have debunked the idea that medical cannabis reduces opioid use. Two large studies published last year found no evidence that legalizing cannabis reduces prescription opioid use, overdose or mortality.

“We tested this relationship and found no evidence that the passage of medical marijuana laws — even in states with dispensaries — was associated with a decrease in individual opioid use of prescription opioids for nonmedical purposes," researchers found.

A 2018 study suggested that cannabis legalization could actually make the opioid crisis worse, concluding that “cannabis use appears to increase rather than decrease the risk of developing nonmedical prescription opioid use and opioid use disorder.”

The Other Side of Cannabis

By Madora Pennington, PNN Columnist

I knew from my friend Nick’s Facebook feed that he was a cannabis enthusiast. His posts preached how it cures pretty much everything and will lead us to world peace.

Nick never tired of encouraging me to try it for my pain from Ehlers-Danlos Syndrome, even as I explained repeatedly that since my mother was psychotic, I avoid all drugs which may cause psychosis. Theoretically, I am at higher risk for that adverse reaction.

Psychosis is a disconnection from reality. A person may have delusions, hallucinations, talk incoherently and experience agitation. Since the 1970s, researchers have been investigating whether cannabis can trigger a psychotic break or full-blown schizophrenia. Daily users of highly potent cannabis are five times more likely to develop psychosis. The risk comes not only from genetic factors, but also from early-life neglect or abuse and even being born in the winter.

Having a rare and complicated medical condition, I get a lot of advice. I took Nick’s insistence I go on cannabis as kindness, as I take all unsolicited health tips. Our social media friendship grew. When my husband and I took a trip to his part of the world, he invited us to stay with him.

Nick picked us up at the train station in the English countryside looking like a dashing movie star. Slim and trim in a crisp Oxford shirt and Ray Bans, spryly maneuvering our luggage, he was still attractive in his 70s. Speaking English like Prince Charles, he confessed, “I am actually a cannabis farmer. I expect no trouble from the local police, but would you prefer to get a hotel room in town?”

My husband and I once risked our lives in the back alleys of Hong Kong to get me a fake Hermes bag. We did not need to consult with each other. We opt for adventure. I would not miss my chance to live a Jane Austen fantasy.

We ate off Nick’s three centuries-old family silver, the forks worn down from hundreds of years of scooting food across the plate. We sat beneath the Regency era portraits of his ancestors. Nick had a room devoted to his cannabis crop, growing fast underneath sun simulating lamps. The odor from the plants permeated his entire country home.

In real life, just as on Facebook, Nick’s favorite subject was the virtues of cannabis. He had been using it since he was a young man. Decades ago, he had spent a couple of years in prison for distribution. Recently his wife had left him over his devotion to marijuana. It was clear from Nick’s stories and life choices that cannabis had created tremendous tension with his family.

We talked of him coming to stay with us in Los Angeles, how we could all go to San Francisco to visit the Haight, as Nick was a genuine 1960s hippie. But leaving home to travel was a problem for him. When he does, he has to ask a friend to tend to his plants, which also means asking the friend to break the law.

Our days with Nick at his charming cottage were governed by his need to partake. Our visits to local sites were cut short, so he could be done driving and functioning for the day, and get home to get high. He did not seem to enjoy the excursions and seemed overwhelmed by being out and about, his anxiety growing, urging us to wrap up and get back home.

Cannabis Side Effects

Like Nick, many people are certain that marijuana helps them get by. On it, life is tolerable and pleasant. Anxiety is calmed. They are out of pain and able to sleep. But are they really benefiting?

At first, marijuana has a calming effect, but over time it negatively changes the way the brain works, causing anxiety, depression and impaired social functioning. With regular use, memory, learning, attention, decision-making, coordination, emotions, and reaction time are impaired. Heavy cannabis use lowers IQ. 

This damage can persist, even after use stops. Teenage users are more likely to experience anxiety, depression and suicidality in young adulthood. According to the CDC, about 1 in 10 marijuana users will become addicted. For people who begin using younger than age 18, 1 in 6 become addicted.

As is the case with other mood-altering substances, cannabis withdrawal symptoms — which include irritability, nervousness, anxiety, depression, insomnia, loss of appetite, abdominal pain, shakiness, sweating, fever, chills and headache — provokes the desire to use.

If someone is using cannabis to escape emotional distress, they never get the chance to deal with underlying problems. Psychiatrist Dr. David Puder recommends to his patients on cannabis that they stop in order to benefit from therapy.

“When they are off of marijuana, they have the ability to be present and really process what they will need to process in therapy in order to get over anxiety and depression,” Puder says, noting that users will often experience a flood of emotions and memories once they stop.

Medical marijuana has been approved for chronic pain and over 50 other health conditions by various states. Whether it actually helps with pain is uncertain. The U.S. Surgeon General warns the potency of marijuana has changed over time and what is available today is much stronger than previous versions. Higher doses of THC (the psychoactive chemical in cannabis) are more likely to produce anxiety, agitation, paranoia and psychosis. Consumers are not adequately warned about these potential harms.

House Guests

Our friend Nick was sure his marijuana use was his choice and that he was not addicted. He insisted my husband and I get high with him.

What is a polite house guest to do? Go along, of course, although we prefer whiskey and a steak. Nick promised we would love it, and that we were free to go upstairs and have sex and open up about anything. We giggled awkwardly. I ingested the smallest possible dose.

Nick then got higher than we had seen him during our entire visit, wolfing down his dinner in minutes. Then, after promising we’d have a tremendous evening of emotional openness and transcendent sharing, he burst into tears recounting how he was the victim of violence in his youth.

I felt for him, it was a horrifying event. Was this unresolved trauma the cause of a lifetime of drug use, denial and self-isolation? We had to wonder. It was truly awkward and uncomfortable, but Nick didn’t seem to remember his outburst. When we returned home, he continued to hound me to take up cannabis.

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

The opinions expressed in this column are those of the author alone and do not inherently reflect the views, opinions and/or positions of Pain News Network.

Coronavirus Is Now More Deadly Than Opioid Crisis

By Roger Chriss, PNN Columnist

The coronavirus pandemic is claiming lives daily. The number of confirmed infections worldwide passed one million today, with over 51,000 deaths.

Case counts in the United States are rising fast, with nearly a quarter of a million people infected and over 5,600 deaths. Over a thousand Americans are now dying every day from COVID-19.

This means that the pandemic is causing more deaths in the U.S. per day than the opioid crisis did in 2017, its worst year. Over 47,000 people died of opioid-related overdoses that year, according to the CDC, or about 128 people a day.

The worst is still ahead of us. The White House coronavirus task force projects that between 100,000 and 240,000 Americans will die from COVID-19.  

Other estimates are higher and some lower. Researchers at the University of Washington project that over the next four months approximately 81,000 people will die from the virus. In other words, the pandemic will kill more Americans in 2020 than opioids did in any year.

If things get worse, because the virus turns more virulent, medical resources dwindle or the public health response weakens, then the estimated death toll may rise into the millions.

Most of us couldn't do anything about the overdose crisis, because it was not an infectious disease epidemic. Practices like social distancing, scrupulous hygiene and self-isolating do not matter in a drug overdose crisis. But for a pandemic viral illness, they are vital.

The importance of distancing cannot be understated. As the University of Oxford Mathematical Institute explains, without distancing an infected person may pass the virus to three people in a week, which in six weeks leads to 1,093 new cases. However, if everyone reduces their contacts by a third, then each infected individual will only infect two others.

Hygiene is similarly important. Regular scrubbing of hands with soap and water, sneezing or coughing safely into an elbow, and strict avoidance of hand-to-face contact can help break the chains of transmission, reduce infection and prevent deaths.  

White House coronavirus response coordinator Dr. Deborah Birx told NBC News that keeping the number of deaths below 200,000 will require that “we do things almost perfectly.”

Early evidence suggests that social distancing and other public health measures are already helping in the San Francisco Bay area and the Seattle-Puget Sound area. But continued vigilance is needed.

“Our model looks at the data to determine if social distancing measures are slowing the spread of COVID-19,” said Dr. Daniel Klein, computational research team leader at the Institute for Disease Modeling. “While the results indicate an improvement, the epidemic was still growing in King County as of March 18th. The main takeaway here is though we’ve made some great headway, our progress is precarious and insufficient.”

Opioid overdoses led to far too many deaths. The pandemic stands to kill far more and lead to vastly more illness. There is a lot we can each do to avoid becoming sick ourselves and protect our families, friends and communities.  

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.

What If the Opioid Crisis Is Worse Than We Think?

By Roger Chriss, PNN Columnist

A recent study in the journal Addiction reports that the opioid crisis in the U.S. may be worse than we’ve been led to believe. The number of overdose deaths linked to legal and illicit opioids over the past two decades could be about 28 percent higher than reported.

Economists Andrew Boslett, Alina Denham and Elaine Hill looked at drug overdose deaths between 1999 and 2016 in the National Center for Health Statistics. Of 632,331 deaths, over one in five had no information on the drugs involved. The researchers estimated that as many as 72% percent of those deaths likely involved opioids. This yields an additional 99,160 deaths involving prescription opioids, heroin, fentanyl and other street drugs that were not counted.

This estimate may or may not be right, but it is definitely not new. Claims like this have been around for years.

In 2017, Business Insider reported on an investigation by CDC field officer Dr. Victoria Hall, who looked at the Minnesota Department of Health's Unexplained Death (UNEX) system. She found that 1,676 deaths in the state had “some complications due to opioid use,” but were not reported as opioid-related deaths.

A 2018 study at the University of Pittsburgh found that as many as 70,000 overdose deaths were missed because of incomplete reporting.

‘Cooking the Data’

It has long been suspected that the CDC’s opioid overdose death toll is faulty – either too high or too low, depending on your point of view. Public health data in the U.S. is shoddy, the result of a fractured and fragmented system that has little central guidance or administrative oversight. The overdose numbers aren’t as reliable as they should be, which raises suspicion they are being manipulated.

The Atlantic makes a similar point about the coronavirus outbreak.

"Everyone is cooking the data, one way or another. And yet, even though these inconsistencies are public and plain, people continue to rely on charts showing different numbers, with no indication that they are not all produced with the same rigor or vigor," wrote Alexis Madrigal. “This is bad. It encourages dangerous behavior such as cutting back testing to bring a country’s numbers down or slow-walking testing to keep a country’s numbers low.”

The implications of under-counting deaths in the overdose crisis require careful consideration. Political campaigns, public policy, state laws and regulations, and clinical practice are built on these numbers. For instance, the Trump administration was recently touting a 4% decline in overdose deaths, but that reduction may not exist.

Similarly, cannabis advocacy groups argue that state legalization has reduced overdose deaths. But again, that reduction may evaporate with better data. State laws and regulations are built on the assumption that trend lines were going in a particular direction. But maybe they aren’t.

Most important, policy groups have argued strenuously that reducing prescription opioid utilization would alleviate the overdose crisis. But if there are vastly more deaths than recognized, where does that leave these groups?

Of course, determining cause of death is a process fraught with difficulties. The New York Times reports that morgues are overburdened and understaffed, many suspected overdose deaths are not fully evaluated, and reporting on the cause of death is not standardized.

Making a probabilistic assessment is even more fraught. For instance, a recent attempt to use stool samples to measure how many rodents, birds and other wildlife are eaten by domestic cats was undone by the discovery that cat food manufacturers regularly change their ingredients.

In other words, there are many known problems and occasional surprises in public health data, so any estimate has to be treated with caution. But if opioid overdoses are vastly undercounted, then we should reassess the policies and politics of the 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.

Overdose Deaths Fell by 4.1% in 2018

By Pat Anson, PNN Editor

A new analysis by the CDC has confirmed earlier estimates that drug overdose deaths in the U.S. decreased by 4.1% in 2018, the first decline in the nation’s overdose rate in nearly three decades.

The decline was led by a drop in overdoses involving prescription opioids (-13.5%) and heroin (-4.1%). Much of that progress was offset by a 10% increase in deaths involving synthetic opioids, a category that includes illicit fentanyl and fentanyl analogs.

Fentanyl and other synthetic opioids were involved in 31,335 overdose deaths -- nearly half of the 70,237 drug deaths in 2018 and over two-thirds of the 46,802 opioid deaths.

The 14,975 deaths linked to prescription opioids represent about 22% of the total number of fatal overdoses.

“Decreases in overdose deaths involving prescription opioids and heroin reflect the effectiveness of public health efforts to protect Americans and their families,” CDC Director Robert Redfield, MD, said in a statement. “While we continue work to improve those outcomes, we are also addressing the increase in overdose deaths involving synthetic opioids. We must bring this epidemic to an end.”

U.S. DRUG OVERDOSE DEATHS IN 2018

SOURCE: CDC

Synthetic opioid deaths in 2018 increased in the Northeast, South and West and remained stable in the Midwest. The highest synthetic opioid death rate (34 deaths for every 100,000 people) occurred in West Virginia, which also has the highest death rate involving prescription opioids (13.1 deaths per 100,000 people).

Seventeen states experienced declines in prescription opioid deaths in 2018, with no states experiencing significant increases.

While opioid prescribing has been declining since 2012, much of the CDC’s public messaging remains focused on reducing the use of opioid pain medication.

“Because of the reductions observed in deaths involving prescription opioids, continued efforts to encourage safe prescribing practices, such as following the CDC Guideline for Prescribing Opioids for Chronic Pain might be enhanced by increased use of nonopioid and nonpharmacologic treatments for pain,” wrote Nana Wilson, PhD, a CDC epidemiologist and lead author of the study.

“Additional public health efforts to reduce opioid-involved overdose deaths include expanding the distribution of naloxone, addressing polysubstance use, and increasing the provision of medication-assisted treatment.”

Wilson and her colleagues noted that an increase in overdose deaths among African-American and Hispanics showed a need for “culturally tailored interventions” to address health and other societal factors.   

While the decline in overdose deaths in 2018 is encouraging, preliminary CDC data indicates the trend is not continuing into 2019. Deaths are increasing from synthetic opioids, cocaine, methamphetamine and psychostimulants such as attention deficit disorder drugs.

Overdose deaths often involve multiple drugs, so a single death might be included in more than one category and be counted multiple times. The quality of the data also varies widely from state to state. Only 39 states have good to excellent overdose data, according to the CDC.

Tweet Led to Dr. Kline Losing His DEA License

By Pat Anson, PNN Editor

A complaint from a woman in upstate New York launched the investigation that recently led to a North Carolina doctor losing his DEA license. Julie Roy doesn’t know Dr. Thomas Kline or any of his patients, but claimed he was dangerous and that “someone can die” because Kline believes opioids are rarely addictive.

Kline surrendered his DEA license to investigators with the North Carolina Medical Board last month.  He is still able to practice medicine but can no longer prescribe opioids and other controlled substances, leaving his 34 patients in medical limbo. All of them suffer from chronic pain and rare diseases that other doctors are increasingly unwilling to treat because they fear coming under scrutiny for opioid prescribing

“I do feel bad for the patients that were affected,” Roy told North Carolina Health News, which first reported on her role in the Kline investigation.

Roy became upset with Kline because he has been an outspoken advocate for pain patients online. Roy’s 26-year old son died from a heroin overdose and she took offense when Kline posted a Tweet last year stating that “opiates work fine without addiction potential” in 99.5% of people.    

She tweeted the North Carolina Medical Board on May 15, saying “this is a doctor that you allow to have an active license. He would love to prescribe every person on earth an opioid.”

NORTH CAROLINA HEALTH NEWS

That same day, Roy made a formal complaint with the medical board against Kline, making a series of unsubstantiated claims about the doctor.

“He is giving out information regarding opioids that is not correct and could cause harm,” she wrote. “I am very concerned as pain patients believe what he says. He says opioids are only addictive to someone who is genetically prone plus a ton of other misinformation.”

Roy even claimed that Kline might be “suffering from substance use disorder himself.”

“The man should not have an active license with his pro opioid perception. The information he puts out alone could cause harm. I would like you to verify (t)hat he is not writing opioid prescription,” Roy wrote.  

Kline Caught Off Guard

Kline responded in writing to Roy’s complaint in July, telling the medical board the information he shared about opioids was accurate and backed up by research. He also denied taking opioids or having a substance use disorder.

“Ms. Roy has lost a son to opiate addiction. Losing a child is the worst of all tragedies. This tragedy could have been avoided with the new knowledge I am presenting in my published research and public talks urging for early identification and treatment of opiate addiction to stop deaths in people like Ms. Roy’s son,” Kline said.

Because none of his patients were harmed by his prescribing and no other complaints were filed against him, Kline thought that would be the end of the matter – even when the medical board asked to review the records of nine of his patients.

Kline was caught off guard when investigators made a surprise visit to his office in Raleigh on February 17 and told him to surrender his DEA license. He did so voluntarily, not realizing at the time that it was unlikely he’d ever get the license back.  

No formal charges have been made against Kline and the medical board won’t comment on the status of the investigation — which could drag on for several more months.

Kline says he’s been able to find new doctors for a handful of his patients, but others are suffering due to untreated pain or running low on their prescriptions.

Ironically, Roy was once a pain patient herself and was on long-term opioid therapy after a failed back surgery. She told NC Health News that her pain medication stopped working, so she switched to buprenorphine (Suboxone), another opioid that’s usually prescribed to treat addiction.

Should Gabapentin Be Used to Treat Alcohol Abuse?

By Pat Anson, PNN Editor

Gabapentin (Neurontin) is so widely prescribed for so many different conditions that a Pfizer executive infamously compared it to “snake oil” in a 1999 email.

“Gabapentin is the snake oil of the twentieth century. It has been successful in just about everything they have studied,” said Christopher Wohlberg, who was a Pfizer Medical Director at the time.

Although only approved by the FDA to treat epilepsy and neuropathic pain caused by shingles, gabapentin is widely prescribed off-label to treat fibromyalgia, anxiety, depression, ADHD, migraine, bipolar disorder, restless leg syndrome and a growing number of other conditions.  

Already the 6th most widely prescribed drug in the United States, gabapentin is also being touted as a treatment for alcohol abuse.

In a small study published in JAMA Internal Medicine, researchers found that gabapentin was effective in treating patients with alcohol use disorder (AUD) – problem drinking that has become severe. Compared to a placebo, gabapentin significantly increased abstinence and reduced heavy drinking days, especially for those who suffer from symptoms of alcohol withdrawal.

“The weight of the evidence now suggests that gabapentin might be most efficacious after the initiation of abstinence to sustain it and that it might work best in those with a history of more severe alcohol withdrawal symptoms,” concluded lead author Raymond Anton, MD, an addiction psychiatrist and professor at the Medical University of South Carolina.

“Armed with this knowledge, clinicians may have another alternative when choosing a medication to treat AUD and thereby encourage more patient participation in treatment with enhanced expectation of success.”

As many as 30 million Americans have AUD, but only about a million are taking a medication to help them reduce drinking or maintain abstinence. The FDA has approved three drugs (naltrexone, disulfiram and acamprosate) for the treatment of alcohol abuse.

Side Effects and Abuse

The suggestion that gabapentin should also be prescribed for AUD comes at a time when the drug is already under scrutiny for its abuse and side effects, including an association with a growing number of suicide attempts. Patients prescribed gabapentin often complain of mood swings, depression, dizziness, fatigue and drowsiness.    

Although the CDC’s controversial 2016 opioid guideline calls gabapentin and its chemical cousin pregabalin “first-line drugs” for neuropathic pain, a recent clinical review found little evidence that either drug should be used off-label to treat pain.

Gabapentin does not carry the same risk of addiction and overdose as opioid pain relievers, but illicit drug users have discovered that gabapentin can heighten euphoria caused by heroin and other illicit opioids. Should a drug like that be used to treat addiction?

Hundreds of clinical studies are underway to find new uses for gabapentin, not only for alcohol abuse, but for a cornucopia of conditions such as obesity, insomnia, breast cancer, asthma, menopause and overactive bladder. One recent study even found that gabapentin improves sexual desire in women with vulvodynia.

Instead of finding new uses for an old medication, maybe it’s time to come up with a new drug.

Dangerous New Street Drug Found in Counterfeit Painkillers

By Pat Anson, PNN Editor

A dangerous new street drug that’s even stronger than fentanyl has been found in counterfeit opioid painkillers seized during a police raid on Canada’s eastern seaboard.

Like fentanyl, isotonitazene is a potent synthetic opioid that is many times stronger than heroin or morphine. In recent months, isotonitazene was detected in over a dozen overdose deaths in Illinois and Indiana, where it was mixed with cocaine. The drug has also recently been found in New Brunswick and Alberta, and has been connected to at least two overdose deaths in Calgary.

Now it is being used to make counterfeit pain medication.

Police in Halifax, Nova Scotia seized 1,900 white tablets from a Halifax home last month while conducting a drug investigation. The pills were sent to Health Canada for a laboratory analysis, which confirmed the tablets were made with isotonitazene.

The pills have an “M” on one side and the number “8” on the other side – making them virtually identical to an 8mg Dilaudid (hydromorphone) tablet.

SOURCE: HALIFAX POLICE

“The appearance of the pill may lead people to believe they are consuming a different drug. Given the potency of the drug, a person may need several doses of naloxone to counter an overdose caused by isotonitazene,” Halifax police said in a statement.

No overdoses have been linked to isotonitazene in Halifax, but police are urging anyone who consumes the pills to seek immediate medical attention.

The Center for Forensic Science Research and Education released a public safety alert last November, when isotonitazene was first linked to overdoses deaths in the Midwest.

“Pharmacological data suggest that this group of synthetic opioids have potency similar to or greater than fentanyl based on their structural modifications,” the alert warns. “The toxicity of isotonitazene has not been extensively studied but recent association with drug user death leads professionals to believe this new synthetic opioid retains the potential to cause widespread harm and is of public health concern.”

Although law enforcement and public health officials have only recently become aware of the threat posed by isotonitazene, illicit drug users have been warning each other about isotonitazene for several months in online message boards.

“I wanted to let the community know that the potency is far above the 60x morphine that's listed online. Everyone should be VERY careful when handling this compound,” one poster warned on Reddit.

Did OxyContin's Reformulation Really Lead to More Heroin Use?

By Roger Chriss, PNN Columnist

A common belief in the opioid overdose crisis is that the reformulation of OxyContin in 2010 led to a large-scale shift to heroin. Seven years after making the pills hard-to-crush to discourage snorting or injecting, The Washington Post reported the abuse-deterrent reformulation had made OxyContin “the chief driver of the explosion in heroin overdose deaths.”

The primary source of this claim is a National Bureau of Economic Research (NBER) paper that states “a substantial share of the dramatic increase in heroin deaths since 2010 can be attributed to the reformulation of OxyContin.”

The NBER paper used data from the National Survey on Drug Use and Health (NSDUH) and the Drug Enforcement Administration to assess usage levels of OxyContin and other prescription opioids, and data from the National Vital Statistics System to measure overdose deaths.

The researchers found that “states with the highest initial rates of OxyContin misuse experienced the largest increases in heroin deaths.”

But this conclusion is now being challenged. A recent study in the journal Addiction Behavior looked at NSDUH data from 2005 through 2014 to evaluate the impact of the reformulation on individuals with a history of OxyContin misuse.

The results showed “no statistically significant effects of the reformulation” on prescription opioid misuse or heroin use. In fact, researchers found a “net reduction in the odds” of heroin initiation after the reformulation.

“Thus, the reformulation of OxyContin appears to have reduced prescription pain reliever misuse without contributing to relatively greater new heroin use among those who misused OxyContin prior to the reformulation,” the authors concluded.

Psych Congress also reported there was little evidence of a shift to heroin from prescription opioids, saying drug trafficking data “don't fully support the often-heard conclusion that efforts to limit access to prescription opioids led to a mass migration to heroin."

Murky Data

The reason for the different conclusions is not clear. But much of what is assumed about abuse-deterrent reformulation is not holding up. Last summer, STAT News reported that rates of OxyContin abuse were similar or higher three years after the drug was reformulated. According to one survey, less than 5 percent of long-term abusers gave up OxyContin, suggesting the reformulation didn’t accomplish much.

Data on heroin use also includes considerable uncertainty, and applying state-level data-sets to understand individual usage patterns is tricky. Plus, data on overdose fatalities can be hard to parse since many victims die with multiple drugs in their systems, and toxicology reporting varies by state.

Since OxyContin’s reformulation, six other opioid medications have been approved by the FDA with abuse deterrent properties, costing drug makers hundreds of millions of dollars in research and development expenses.

Figuring out what happens after a prescription opioid is reformulated is important. Current public health policy and prescribing practices are assuming risks and benefits based on limited evidence. If something different or perhaps more complex is happening, then we need to look harder and make changes.

The implications here are also important, including determining liability and damages in the opioid lawsuits, developing effective public health measures for addiction treatment and the overdose crisis, and creating better risk assessment for pain management.

The impacts of the OxyContin reformation may be smaller and more subtle than previously thought. If the new findings hold, then we may have to rethink the benefits of abuse-deterrent formulations and the trajectory of heroin use. In other words, we need to keep looking closely at the overdose crisis and not assume we have it fully figured out.

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

Is It Too Early to Declare Victory in the Opioid Crisis?

By Pat Anson, PNN Editor

Wisconsin’s two U.S. Attorneys are taking a victory lap on the one-year anniversary of threatening letters they sent to 180 doctors, physician assistants and nurse practitioners in the state. The letters warned the providers that if they continue to prescribe “relatively high levels” of opioid medication — above doses recommended by the CDC — they could face civil or criminal prosecution.

In a joint news release this week, Scott Blader and Matthew Krueger, U.S. Attorneys for the Western and Eastern Districts of Wisconsin, said there has been “a substantial decrease in opioid prescribing” among providers who received the warning letters.

“Thanks partly to this initiative and the consistent efforts by the Wisconsin medical community to stem over-prescribing, Wisconsin has seen substantial progress in the fight against opioid abuse,” the news release claimed. “Total opioid prescriptions in Wisconsin have declined by 30 percent between 2016 and 2019, according to data from the Wisconsin Prescription Drug Monitoring Program. The letters sent by the United States Attorneys appear to have amplified this downward trend.” 

The release did not indicate if any provider who received the warning letter had been charged with a crime or if any of their patients has been harmed by their prescribing. The two U.S. Attorneys’ offices did not respond to a request for further information.

President Trump also claimed progress was being made in the overdose crisis during his State of the Union address on Tuesday.

“We are curbing the opioid epidemic, Drug overdose deaths declined for the first time in nearly 30 years. Among the states hardest hit, Ohio is down 22 percent, Pennsylvania is down 18 percent, Wisconsin is down 10 percent — and we will not quit until we have beaten the opioid epidemic once and for all,” Trump said.

Fentanyl Deaths Increasing

A closer look at the overdose numbers shows that it’s way too early to declare victory. A CDC report last week found that drug deaths declined over 4% in 2018, led by a significant drop in overdoses involving hydrocodone, oxycodone and other painkillers. But deaths linked to illicit fentanyl and other street drugs are surging – threatening to reverse the overall trend.

“One thing that we’re seeing is that the decline doesn’t appear to be continuing in 2019. It appears rather flat, maybe actually increasing a little bit,” said Robert Anderson, PhD, Chief of the Mortality Statistics Branch, National Center for Health Statistics. “We do know that deaths due to synthetic opioids like fentanyl are continuing to increase into 2019 and we’re seeing increases similarly with cocaine and psychostimulants with abuse potential, the methamphetamine deaths."

The most recent overdose stats from Wisconsin are also revealing, as the following two charts will show. While deaths in the state involving prescription opioids began declining in October 2017 -- over a year before the U.S. Attorneys even sent their warning letters – overdoses linked to fentanyl and other synthetic opioids are rising.

SOURCE: WISCONSIN DEPARTMENT OF HEALTH SERVICES

Nearly twice as many Wisconsinites are dying from heroin and fentanyl overdoses than from prescription opioids – a fact that is omitted in the news release from the U.S. Attorneys.

The only mention of fentanyl was the kind available by prescription. Prosecutors took credit for a Wausau physician being sentenced to three months in prison for writing “fraudulent fentanyl prescriptions” to six patients.  

A better representation of what’s happening in Wisconsin – and around the nation – is last month’s arrests of over three dozen people accused of trafficking illicit fentanyl, heroin and cocaine in Milwaukee. The drugs were allegedly shipped from Puerto Rico and Mexico, meaning drug cartels thousands of miles away recognize that there’s a demand for street drugs in Wisconsin’s largest city.

In 2019, 370 people died of drug overdoses in Milwaukee County. It was iIlicit fentanyl — not prescription opioids — that was the leading cause of death.

That doesn’t deserve a victory lap.

DEA: Fentanyl 'Primary Driver' of Overdose Crisis

By Pat Anson, PNN Editor

The U.S. Drug Enforcement Administration has released the 2019 National Drug Threat Assessment, a comprehensive report that outlines the threats posed to the nation by drug traffickers and the abuse of illicit drugs.

Not surprisingly, the annual report found that illicit fentanyl is the “primary driver” behind the overdose crisis, with fentanyl and its analogs involved in more overdose deaths than any other illicit drug. Fentanyl is a synthethic opioid 50 to 100 times more potent than morphine. The drug is prescribed legally to treat severe pain, but illicit versions of fentanyl have flooded the black market.

Of growing concern to the DEA is the appearance of illegal pill press operations in the U.S. that are manufacturing millions of counterfeit painkillers and other medications, using fentanyl powder smuggled in from China and Mexico.

“Fentanyl will remain a serious threat to the United States as record numbers of individuals suffer fatal overdoses from illicit fentanyl sourced to foreign clandestine production,” the report warns.

“Clandestine fentanyl pill pressing operations will likely increase as DTOs (drug trafficking organizations) seek to appeal to the large pill abuser population in the United States, with counterfeit fentanyl-containing pills continuing to be associated with clusters of overdoses and deaths due to inconsistent mixing and often unexpectedly high potency.”

With China cracking down on illicit fentanyl laboratories, the DEA expects the primary source of fentanyl production to shift to Mexico and India.  

Fewest Prescription Opioids Since 2006

One bright spot in the DEA report is the continuing decline in overdoses involving prescription opioids. As PNN reported, overdose deaths involving natural and semisynthetic opioids, which include painkillers such as oxycodone and hydrocodone, were 3.8% lower in 2018 than in 2017.   

The DEA said the supply of prescription opioids is now at its lowest level since 2006. DEA production quotas for hydrocodone and oxycodone have been cut nearly in half since 2016, with further cuts proposed for 2020.

But while the retail supply of opioid medication has fallen dramatically, the diversion of opioids and other controlled drugs by medical professionals and wholesale distributors – so-called “lost in transit” diversion – has soared. There were 18,604 lost in transit reports filed in 2018, nearly six times the number reported in 2010.

“It is unclear if these dosage units are being diverted, destroyed, or truly lost. Although representative of only a small number of DEA registrants, diversion by physicians, nurses, and other medical professionals and their staff remains a threat to communities across the United States,” the report warns.

The DEA predicts “a steady decrease” in the supply of opioids over the next several years and that prescription drug abusers “may shift to abusing heroin, illicitly produced synthetic opioids, and methamphetamine to obtain similar effects, which may further increase overdose deaths through at least 2020.”

The DEA said the threat posed by psychostimulants such as methamphetamine and cocaine is “worsening and becoming more widespread.” While most cocaine users prefer to snort or inject the drugs, law enforcement agencies are starting to find cocaine in tablet or pill form.

“Whether these instances are harbingers of a new trend, an experiment, or simply the result of accidental contamination within poly-drug operations remains to be seen. Tableting and capsulizing cocaine may allow traffickers to capitalize on the considerably larger CPD user market with a different version of cocaine, further maximizing profits,” the DEA said.

Finally, while the DEA officially considers the herbal supplement kratom a “drug of concern” and once tried to ban it, there is once again no mention of kratom in its annual drug threat assessment.

Drug Overdose Deaths Fell 4% in 2018

By Pat Anson, PNN Editor

Drug overdose deaths in the United States dropped in 2018 for the first time in nearly three decades, according to a new CDC report that highlights the rapidly changing nature of the overdose crisis. While deaths linked to many prescription opioids declined, overdoses involving illicit fentanyl, cocaine and psychostimulants rose.

There were 67,367 drug overdose deaths in the U.S. in 2018, a 4.1% decline from 2017 when there were 70,237 fatal overdoses.

The rate of overdose deaths involving natural and semisynthetic opioids, which includes painkillers such as oxycodone and hydrocodone, was 3.8% lower. There were nearly 2,000 fewer deaths linked to painkillers in 2018 than there was the year before.

However, the decline in deaths involving opioid medication was more than offset by a continuing spike in overdoses linked to synthetic opioids other than methadone, which primarily involves illicit fentanyl and fentanyl analogs. The death rate in that category rose 9% from 2017 to 2018.

SOURCE: CDC

While the overall trend is encouraging, a top CDC official was cautious about preliminary data for drug deaths in 2019.

“One thing that we’re seeing is that the decline doesn’t appear to be continuing in 2019. It appears rather flat, maybe actually increasing a little bit,” said Robert Anderson, PhD, Chief of the Mortality Statistics Branch, National Center for Health Statistics.

“We do know that deaths due to synthetic opioids like fentanyl are continuing to increase into 2019 and we’re seeing increases similarly with cocaine and psychostimulants with abuse potential, the methamphetamine deaths."

Overdose deaths often involve multiple drugs, so a single death might be included in more than one category and be counted multiple times. A death that involved both fentanyl and cocaine, for example, would be classified by CDC researchers as an overdose involving both synthetic opioids and cocaine.

“There’s a lot of overlap between these categories and so a death may be actually counted in multiple categories, in two or more in many instances, making it difficult to partition the decline,” said Anderson. “We really don’t have a good handle on how best to do that.”  

Opioid Prescriptions Decline Significantly

A second CDC study on opioid prescribing shows that prescriptions have declined significantly in 11 states with prescription drug monitoring programs (PDMPs) that participate in the Prescription Behavior Surveillance System (PBSS). The 11 states include California, Ohio, Texas and Florida, and represent over a third of the U.S. population.

The decline in opioid prescriptions in the states ranged from 14.9% to 33% from 2010 to 2016, indicating that prescriptions were falling long before the CDC released its controversial opioid guideline in March, 2016. Significant declines were also noted in high dose opioid prescriptions, the average daily dose and in prescriptions obtained from multiple providers.

Despite the nearly decade-long decline in prescriptions, CDC researchers continue to blame opioid medication for the ongoing overdose crisis, offering little evidence to support that view.

“PDMP data collected by PBSS indicate that steady progress is being made in reducing the use and possible misuse of prescription-controlled substances in the United States. However, some persons who were misusing prescription opioids might have transitioned to heroin or illicitly manufactured fentanyl, a change that has made the drug overdose epidemic and associated overdose rates more complex,” researchers said.

“Because the opioid overdose epidemic began with increased deaths and treatment admissions related to opioid analgesics in the late 1990s, initiatives to address overprescribing might eventually result in fewer persons misusing either prescription or illicit drugs. Reduction in overprescribing opioids might lead ultimately to a decrease in overall overdose deaths.”

PDMP data for the CDC study came from the PBSS monitoring program at Brandeis University, where Dr. Andrew Kolodny is Co-Director of the Opioid Policy Research Collaborative. Kolodny is the founder and Executive Director of Physicians for Responsible Opioid Prescribing (PROP), an activist group that has long been critical of opioid prescribing.

Alcohol Deaths Double in U.S.

By Pat Anson, PNN Editor

Alcohol related deaths in the U.S. have doubled in the past two decades, according to a new study that highlights an under-reported aspect of the overdose crisis: while deaths involving prescription opioids are declining, alcohol abuse appears to be increasing.

Researchers at the National Institute on Alcohol Abuse and Alcoholism (NIAAA) found the number of death certificates mentioning alcohol more than doubled from 35,914 in 1999 to 72,558 in 2017.

By comparison, 17,029 deaths in 2017 involved a prescription opioid, according to CDC estimates.

“The current findings suggest that alcohol-related deaths involving injuries, overdoses and chronic diseases are increasing across a wide swath of the population. The report is a wakeup call to the growing threat alcohol poses to public health,” said NIAAA Director Dr. George Koob.

Nearly 1 million alcohol-related deaths were recorded between 1999-2017. About half the deaths resulted from chronic liver disease or overdoses on alcohol alone or with other drugs.

Researchers noted that alcohol-related deaths were increasing among people in almost every age, race and ethnic group. Their study is published in Alcoholism: Clinical & Experimental Research.

“Taken together, the findings of this study and others suggests that alcohol-related harms are increasing at multiple levels – from ED visits and hospitalizations to deaths. We know that the contribution of alcohol often fails to make it onto death certificates. Better surveillance of alcohol involvement in mortality is essential in order to better understand and address the impact of alcohol on public health,” said Koob.

Other drugs besides alcohol are increasingly involved in overdoses. A recent analysis of over one million urine drug tests conducted by Millennium Health found that positive results for illicit fentanyl rose by 333% since 2013, while positive rates for methamphetamine increased by 486 percent.

That study, published in JAMA Network Open, found that positive rates for heroin and cocaine peaked in 2016 and appear to be declining.

The analysis is similar to a 2019 report from the National Institute on Drug Abuse, which found that drug deaths involving prescription opioids and heroin have plateaued, while overdoses involving methamphetamine, cocaine and benzodiazepines have risen sharply.

Unreliable Data

Just how reliable is the federal data on drug use and overdoses? Not very, according to another study published in Drug and Alcohol Dependence.

Troy Quast, PhD, an associate professor at the University of Florida’s College of Public Health, compared overdose data from the Florida Medical Examiners Commission (FMEC) to drug deaths in a CDC database. Quast found the federal data significantly undercounted overdose deaths in Florida linked to cocaine, benzodiazepines, amphetamines and other drugs.

Florida medical examiners are required by law to wait for complete toxicology results before submitting an official cause of death to FMEC. It often takes weeks or months to identify the exact drug or drugs that cause an overdose. By contrast, the CDC data is based on death certificates filed by coroners and other local authorities, which often don't include detailed toxicology reports. This causes significant differences between the two databases.

Between 2003 and 2017, roughly one-in-three overdose deaths in Florida involving illicit or prescription opioids were not reported by the federal government. The discrepancy wasn’t limited to opioids. Quast also found that nearly 3,000 deaths in Florida caused by cocaine were not included in the CDC database. Overdose deaths involving benzodiazepines and amphetamines were also significantly under-reported.

"The CDC data are widely reported in the news and referenced by politicians, which is problematic since those estimates significantly undercount the true scope of the epidemic for specific drugs," said Quast. "The rate of under-reporting for all overdose deaths in Florida is near the national average, so the problem is not to the state."

This isn’t the first time the reliability of CDC data has been questioned. In 2018, CDC researchers admitted that many overdoses involving illicit fentanyl and other synthetic black market opioids were erroneously counted as prescription drug deaths. As result, federal estimates prior to 2017 "significantly inflate estimates" of prescription opioid deaths.

Even the adjusted estimates are imprecise, because the number of deaths involving diverted prescriptions or counterfeit drugs is unknown and drugs are not identified on 20% of death certificates. When the drugs are listed, many overdoses are counted multiple times by the government because more than one substance is involved.

The federal government is working to improve the collection of overdose data. Over 30 states are now enrolled in the CDC's Enhanced State Opioid Overdose Surveillance program, which seeks to improve overdose data by including toxicology reports and hospital billing records.

In 2017, the program reported that nearly 59 percent of overdose deaths involved illicit opioids like fentanyl and heroin, while 18.5% had both illicit and prescription opioids. Less than 18% tested positive for prescription opioids only.

A recent study of drug deaths in Massachusetts found that only 1.3% of overdose victims who died from an opioid painkiller had an active prescription for the drug – meaning the medication was probably diverted, stolen or bought on the street.  

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.