Trump Commission Seeks More Limits on Rx Opioids

By Pat Anson, Editor

President Trump’s opioid commission released its final report Wednesday, an ambitious list of over four dozen recommendations aimed at treating addiction, preventing overdoses, and further restrictions on opioid prescribing.   

“This crisis can be fought with effective medical education, voluntary or involuntary changes in prescribing practices, and a strong regulatory and enforcement environment,” the commission said in its report.

The president established the commission in March to give him a list of recommendations to combat drug addiction and the overdose crisis. 

“Our people are dying. One hundred seventy-five people a day, every day, are dying in the United States from this epidemic,” said commission chairman Gov. Chris Christie of New Jersey, one of five politicians who served on the six member panel.

“If a terrorist organization was killing 175 Americans every day on American soil, what would you be willing to pay to make it stop? I think we’d be willing to do anything and everything to make it stop. And that’s the way we now need to see this, because this is an attack from within. We are killing ourselves.”

The commission’s 131-page report did not spell out how much money would be needed to implement the panel’s wish list of 56 recommendations.

Chief among them was to get drug makers and the National Institutes of Health to work together developing new non-opioid painkillers and addiction treatment medications.

“It is inexcusable that the major pharmaceutical companies in this country have stood on the sidelines during this crisis. And they have,” said Christie.

New Prescribing Guideline to Supplement CDC's

The commission is also recommending that a new set of guidelines for opioid prescribing be developed to “supplement” the guideline released last year by the Centers for Disease Control and Prevention.  It was not immediately clear if the new guidelines would replace, weaken or strengthen the CDC’s recommendations, or simply expand their use throughout the healthcare system.

“An updated set of guidelines for prescription pain medications should be established by an expert committee composed of various specialty practices to supplement the CDC guideline that are specifically targeted to primary care physicians,” the report says.

The commission recommended that federal regulators require patients to give informed consent about the risks and alternatives to opioid painkillers before the medication is prescribed to them. The panel also called for a new “national curriculum and standard of care” for opioid prescribers, and that pharmacists be trained to recognize and deny “inappropriate prescriptions.”

The commission urged the federal government to work with states to improve the toxicology data on overdose deaths by developing uniform forensic drug testing. Critics say the current data now being used by federal agencies is flawed or cherry-picked. 

“We do not have sufficiently accurate and systematic data from medical examiners around the country to determine overdose deaths, both in their cause and the actual number of deaths,” the report says.

No Limit on Opioid Supply for Acute Pain

The commission did not recommend that supply limits be placed on opioid prescriptions for short term pain, as many expected. Several states have already enacted 5 or 7-day limits on opioids for acute pain. The panel also did not endorse the development of marijuana-based medications, which many pain sufferers are now using as an alternative to opioids.

Most of the commission’s other recommendations deal with cracking down on drug traffickers and the illicit drug market, expanding the drug court system, and increasing access to addiction treatment.

Gov. Christie refuted criticism of President Trump for declaring the overdose crisis a public health emergency, instead of a national emergency. Only $57,000 in federal funding is currently set aside to deal with a public health emergency.

“The president did exactly what I asked him to. I wanted this to be a public health emergency because I wanted HHS (Department of Health and Human Services) to administer the funds, not FEMA (Federal Emergency Management Agency). No offense to FEMA. They’re busy with some other things and it’s not there area of expertise,” Christie said.

“Now it’s incumbent upon Congress to step up and put money in the public health emergency fund, so the president can utilize that. And that should happen without delay in the view of the commission.”

In addition to Christie, commission members include Gov. Charlie Baker of Massachusetts, Gov. Roy Cooper of North Carolina, Florida Attorney General Pam Bondi, Bertha Madras, PhD, a professor of psychobiology at Harvard Medical School, and Patrick Kennedy, a former Rhode Island congressman.

In its fifth and final hearing, the commission heard testimony from several people who lost loved ones to opioid addiction and overdose. The panel never asked for or received testimony from pain sufferers, patient advocates or pain management physicians.

Fentanyl Linked to Over Half of Opioid Overdoses

By Pat Anson, Editor

A new report from the Centers for Disease Control and Prevention shows that illicit fentanyl – not prescription pain medication -- was involved in over half of the recent opioid overdoses in ten states.

The report underscores the changing nature of the nation’s overdose crisis and how public health officials have been slow to respond to the growing role of fentanyl and other illegal opioids – focusing instead on limiting access to opioid medication.

CDC researchers say fentanyl or its chemical cousins (known as fentanyl analogs) were detected in 2,903 of 5,152 opioid overdoses (56.3%) during the last six months of 2016.

Their report on overdoses in ten states (Oklahoma, New Mexico, Wisconsin, West Virginia, Ohio, Maine, Missouri, Rhode Island, Massachusetts and New Hampshire) is the first to use toxicological and death scene evidence to characterize opioid overdoses, a method that is far more accurate than other CDC reports that rely on death certificate codes.

source: Centers for disease control and prevention

Maine, Massachusetts, New Hampshire, Rhode Island and Missouri reported the highest percentages of deaths involving fentanyl (60-90%), while New Mexico and Oklahoma had the lowest (15-25%). Fentanyl is a potent synthetic opioid that is legally prescribed to treat severe pain. The vast majority of the deaths, however, involve illicit fentanyl that has flooded the black market in recent years. 

“This analysis of opioid overdose deaths in 10 states participating in the ESOOS (Enhanced State Opioid Overdose Surveillance) program found that illicitly manufactured fentanyl is a key factor driving opioid overdose deaths and that fentanyl analogs are increasingly contributing to a complex illicit opioid market with significant public health implications,” the researchers reported.

“Illicitly manufactured fentanyl is now a major driver of opioid overdose deaths in multiple states, with a variety of fentanyl analogs increasingly involved, if not solely implicated, in these deaths. This finding raises concern that in the near future, fentanyl analog overdose deaths might mirror the rapidly rising trajectory of fentanyl overdose deaths that began in 2013 and become a major factor in opioid overdose deaths.”

The CDC recently expanded the ESOOS program to 32 states and the District of Columbia. Additional funding was also provided to improve toxicology testing for a wider range of fentanyl analogs such as carfentanil, which is estimated to be 10,000 times more potent than morphine.

The new CDC report did not detail how many of the overdose deaths involved prescription opioids. A recent report from Massachusetts  estimated that prescription opioids were involved in only about 15% of overdoses in that state, ranking well behind cocaine, benzodiazepines, heroin and fentanyl.

source: massachusetts department of public health

Although opioid prescribing has been in decline for years, public health efforts remain focused on limiting access to pain medication. As PNN has reported, the CDC recently launched a new advertising campaign that focuses exclusively on raising awareness about the risks of prescription opioids, while ignoring the role of fentanyl and heroin in the overdose crisis.

The CDC’s Rx Awareness campaign will initially run in four states -- including Massachusetts and Ohio, two of the states where fentanyl overdoses vastly outnumber those involving pain medication.

How the DEA Changed the Overdose Numbers

By Pat Anson, Editor

The Drug Enforcement Administration has released its annual report on the threat posed to the U.S. by drug trafficking and the abuse of illicit drugs.

The 2017 National Drug Threat Assessment (NDTA) has both good and bad news about the nation’s worsening overdose crisis. But like other federal agencies, the DEA has a disturbing tendency to massage statistics to make the role of opioid pain medication more significant than it actually is.

“The threat posed by controlled prescription drug (CPD) abuse is prevalent. Every year since 2001, CPDs, specifically opioid analgesics have been linked to the largest number of overdose deaths of any illicit drug class, outpacing those for cocaine and heroin combined,” the report declares.

That sure makes it sound like opioid pain medication is killing more people than ever before, doesn’t it? A closer look at the numbers and methodology used by the DEA suggests otherwise.

"Controlled prescription drugs" is a very broad category that includes not only opioid pain relievers, but anti-anxiety drugs (Valium, Xanax), stimulants (Adderall, Ritalin), and anabolic steroids. And there's plenty of evidence people are dying from those drugs as well.

This is not the first time the DEA has lumped opioid pain relievers with other drugs. In the 2016 NDTA, the DEA combined opioids with anti-anxiety drugs, but not stimulants or steroids.

A year earlier, in the 2015 NDTA, prescription opioids were in a category all to themselves.

The effect of these changing and broadening definitions is significant. Every year the overdose crisis appears to be getting worse and worse. It certainly is for deaths linked to illicit drugs like heroin, cocaine and fentanyl, but not necessarily for prescription drugs and definitely not for opioid pain medication.

One has to wonder why these definitions keep changing and distorting the true nature of the overdose crisis. Don’t take my word for it. Look at how the overdose numbers for "Selected Illicit Drugs" in 2013 have grown over the years.

In the 2015 NDTA, the DEA reported that an “opioid analgesic” was involved in the deaths of 16,235 Americans in 2013.

In the 2016 NDTA, the DEA reported that “prescription drugs” were involved in the deaths of 22,767 Americans in 2013.

And in the 2017 NTDA, the DEA reported that “medications” were involved in the deaths of 24,536 Americans in 2013. The "medications" category includes not only controlled prescription drugs, but over-the-counter drugs as well.

Simply by changing the way they counted overdoses, the DEA and other federal agencies raised the death toll for 2013 by over 8,300 people.  We’re only using 2013 as an example.  From one report to the next, overdoses grew for every other year as well.

This isn’t the first time the federal government has played around with the overdose numbers. As PNN reported, last December the CDC and the White House Office of National Drug Control Policy released three different estimates of how many Americans died in 2015 from overdoses linked to prescription opioids.  

Within one week, the overdose numbers evolved from 17,536 deaths, down to 12,700, and then back up to 15,281 deaths. To use a football metaphor, that is known as moving the goalposts.

Pain Medication Abuse Declining

A closer reading of the 2017 NDTA shows that heroin, illicit fentanyl and other illegal drugs are now driving the overdose crisis, not opioid pain medication. Less than one percent of legally prescribed opioids are being diverted to the black market. 

A recent survey of law enforcement agencies, known as the National Drug Threat Survey, found that less than 10 percent of respondents nationwide believed controlled prescription drugs were the greatest drug threat in their jurisdiction -- down considerably from 2014 when over 21.5 percent reported the same

The abuse of prescription opioids is also declining. Fewer Americans are testing positive for hydrocodone, oxycodone and other painkillers in workplace drug tests. And the number of people seeking treatment for abusing pain medication has fallen significantly. From 2011 to 2014, admissions to publicly-funded treatment facilities for prescription opioid abuse fell by nearly a third. 

“This decline can in part be attributed to CPD (controlled prescription drugs) abusers switching to heroin or other illicit opioids. Some CPD abusers, when unable to obtain or afford CPDs, begin using heroin as a cheaper alternative offering similar opioid-like effects,” said the DEA.

“Expansion of the counterfeit pill market, to include pills containing fentanyl, threatens to circumvent efforts by law enforcement and public health officials to reduce the abuse of opioid medications; the arrival of large amounts of counterfeit prescription drugs containing fentanyl on the market replaces opioid medications taken off of the street.”

Curiously, the DEA report doesn’t even list kratom as a drug threat – even though the agency considers the herbal supplement a “drug of concern” and tried to ban it last year. 

“I think that all of us in the kratom community have a hard time reconciling the lack of a threat listing for kratom and yet still being considered a drug of concern,” said Dave Herman, chairman of the American Kratom Association, a pro-kratom consumer group.  “The science tells us that kratom has a low potential for either abuse or addiction and we hope to see that reflected in all DEA materials.”

Whether its kratom or pain medication, the DEA and other federal agencies have a responsibility to be consistent and to get their facts right.  Inflating the overdose numbers and blaming opioid medication may make for good headlines, but it diverts funding, resources and policymakers away from other drug problems that truly need more attention. We'll never get a handle on the overdose crisis if we keep moving the goalposts.

A recent editorial in the Journal of Pain Research took the CDC to task for doing just that.

"Transparency, freedom from bias, and accountability are, in principle, hallmarks of taxpayer-funded institutions. Unfortunately, it seems that at least one institution, the Centers for Disease Control and Prevention, continues to struggle with all three," wrote researchers Michael Schatman, PhD, and Stephen Ziegler, PhD.

"What began with a prescribing guideline created in secrecy has now evolved to the use of statistical data and public statements that fail to capture not only the complexity of the problem but also the distinction between licit and illicit opioids and their relationship to the alarming increase in unintentional overdose. This is unfortunately consistent with Mark Twain’s assertion that 'there are lies, there are damn lies, and then there are statistics.'"

What is Opioid Use Disorder?

By Rochelle Odell, Columnist

You’ve probably heard or seen the phrase “Opioid Use Disorder.”  It’s a broad term currently being used to describe not only opioid addiction, but patterns of behavior that might be a sign of addiction or could lead to it.

If that sounds like they’re putting the cart before the horse, it’s because they are.

In order to understand Opioid Use Disorder, one must understand the government's stance on opioids. The National Institute on Drug Abuse – which is part of the National Institutes of Health (NIH) – lays it out in a recently revised statement on the opioid crisis:

“Every day, more than 90 Americans die after overdosing on opioids. The misuse of and addiction to opioids--including prescription pain relievers, heroin and synthetic opioids such as fentanyl--is a serious national crisis that affects public health as well as social and economic welfare."

Notice how they lump prescription pain relievers in with heroin and illicit fentanyl?  The more I research, the more I find this common thread of illogical thinking. The government consistently lumps pain medication in with illicit drugs.

Here’s another example from the NIH: 

“In 2015, more than 33,000 Americans died as a result of an opioid overdose, including prescription opioids, heroin, and illicitly manufactured fentanyl, a powerful synthetic opioid.

That same year, an estimated 2 million people in the United States suffered from substance use disorders related to prescription opioid pain relievers, and 591,000 suffered from a heroin use disorder.”

Substance use disorders “related” to pain relievers? Heroin use disorder? That got me wondering how many drug “disorders” there are.

According to the Substance Abuse and Mental Health Services Administration (SAMSHA), there are six major substance use disorders. Nearly 93,000,000 Americans have a substance use disorder of some kind:

1) Alcohol Use Disorder (AUD): About 17 million Americans have AUD. According to the CDC, alcohol causes 88,000 deaths a year. 

2) Tobacco Use Disorder: Nearly 67 million Americans use tobacco. According to the CDC, cigarette smoking causes more than 480,000 deaths a year.

3) Cannabis Use Disorder: Over 4 million Americans meet the criteria for a substance use disorder based on their marijuana use. No estimate is provided on the number of deaths caused by marijuana, if any.

4) Stimulant Use Disorder:  This covers a wide range of stimulant drugs that are sometimes used to treat obesity, attention deficit hyperactivity and depression. The most commonly abused stimulants are amphetamine, methamphetamine and cocaine. Nearly 2 million Americans have a stimulant use disorder of some kind.

5) Hallucinogen Use Disorder: This covers drugs such as LSD, peyote and other hallucinogens. About 246,000 Americans have a hallucinogen use disorder.

6) Opioid Use Disorder: Again, this covers both illicit opioids and prescription opioids. In 2014, an estimated 1.9 million Americans had an opioid use disorder related to prescription pain relievers and 586,000 had a heroin use disorder (notice the SAMSHA numbers are somewhat different from what the NIH tells us).

But what exactly is Opioid Use Disorder?  Does it mean 2.5 million Americans are addicted to opioids?

No.

The diagnostic codes used to classify mental health disorders were revised in 2013 to cover a whole range of psychiatric symptoms and treatments. Two disorders – “Opioid Dependence” and “Opioid Abuse” -- were combined into one to give us “Opioid Use Disorder.” Few recognized at the time the significance of that change, it's impact on pain patients, or how it would be used to inflate the number of Americans needing addiction treatment.

Elizabeth Hartley, PhD, does a good job explaining what Opioid Use Disorder is in an article for verywell.

Hartley wrote that Opioid Use Disorder can be applied to anyone who uses opioid drugs (legal or illegal) and has at least two of the following symptoms in a 12 month period:

• Taking more opioids than intended
• Wanting or trying to control opioid use without success
• Spending a lot of time obtaining, taking or recovering from the effects of opioids
• Craving opioids
• Failing to carry out important roles at home, work or school because of opioid use
• Continuing to use opioids despite relationship or social problems
• Giving up or reducing other activities because of opioid use
• Using opioids even when it is unsafe
• Knowing that opioids are causing a physical or psychological problem, but using them  anyway
• Tolerance for opioids.
• Withdrawal symptoms when opioids are not taken.

The last two criteria will apply to almost every chronic pain patient on a prescription opioid regimen. So might some of the others. Most of us develop a tolerance for opioids, and if they are stopped or greatly reduced, we will experience withdrawal symptoms.  We simply cannot win for losing. 

If you learn your physician has diagnosed you with Opioid Use Disorder, be sure to ask them what criteria were used and why was it selected. Ask if you should see a doctor more knowledgeable about diagnostic codes and psychiatric disorders. 

Remember, knowledge is power. Take this information with you on your next visit to the doctor if you suspect you have been diagnosed with Opioid Use Disorder and your medications have been cut or reduced.

I hope what I have written helps you further understand exactly what we are facing and why. To be honest, it makes me want to wave the white flag, but I know that cannot happen.  We have to fight. Fight for proper care for a chronic disease or condition we didn't ask for or want. We can’t live the rest of our lives in severe, debilitating pain when effective treatment is available.  

Rochelle Odell lives in California. She’s lived for nearly 25 years with Complex Regional Pain Syndrome (CRPS/RSD).

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.

What Makes Buprenorphine Risky for Pain Patients

By Jane Babin, Guest Columnist

Buprenorphine is the darling of the addiction treatment industry, rapidly replacing methadone as the "medication assisted treatment" of choice for opioid use disorder (OUD) and addiction.  

Unlike methadone, which can only be dispensed through an opioid treatment program, buprenorphine can be prescribed in the privacy of a physician's office and filled at a pharmacy.  As a class III controlled substance, prescriptions for buprenorphine can be phoned or faxed in, and scripts can be refilled up to 5 times in 6 months without a new prescription.

Class II controlled substances, like hydrocodone, oxycodone and morphine, require a new prescription each month and can neither be refilled nor phoned in.

The only federal limitations on prescribing buprenorphine for OUD is that a physician must complete mandatory education and treat only a limited number of patients (currently 275). 

Ironically, these restrictions do not apply when buprenorphine is prescribed off-label for pain, leading some physicians and patients to turn to buprenorphine for chronic pain as class II opioids become increasingly harder to get.

Yet without training on buprenorphine’s unique pharmacology and its implications, physicians treating chronic pain may be unaware of the risks it presents. Let me explain why.

Buprenorphine’s Effect on Other Opioids

Buprenorphine is an opioid that acts as an agonist of the mu opioid receptor (MOR), which causes pain relief, just like class II opioids.  It also has side effects similar to other opioids, including tolerance, dependence, abuse potential, constipation, sedation and potentially fatal respiratory depression. 

What distinguishes buprenorphine from other opioids is that it is only a partial MOR agonist (50%).  Thus the effects of buprenorphine -- both pain relief and the undesirable side effects – don’t exceed half that of other, full agonist opioids.

Buprenorphine also has a ceiling of maximum effectiveness that reaches a plateau as the dosage is increased. That ceiling is well below what can be obtained with morphine and other opioids, but the side effects can still lead to death in opioid-naïve patients.  Buprenorphine has a long plasma half life, binds very strongly to MOR, and remains bound for extended periods of time.  Its usefulness in treating OUD is believed to lie in these properties, because it activates MOR sufficiently to curb drug craving, but not enough to elicit the euphoric effects that can lead to addiction. 

When an opioid that has higher analgesic potency, but lower MOR affinity, such as morphine or heroin, is also administered, buprenorphine wins the battle to bind and remains bound to MOR.  It can displace both heroin and naloxone from MOR, but neither can displace buprenorphine.  Naloxone can be effective when co-administered with buprenorphine -- as it is in combination drugs such as Suboxone -- but not after the administration of buprenorphine. 

Buprenorphine is also a kappa opioid receptor antagonist, which is thought to further reduce euphoria and addictive reinforcement. That’s great for patients with OUD, because it helps them resist the temptation to abuse opioids, and dampens or eliminates the euphoric effect of heroin or other opioids should they relapse.  

Increasingly, buprenorphine is being advocated for chronic pain patients.  With no more "proof" of efficacy for treating chronic pain than any other opioid, it has emerged as a less objectionable opioid because it appears safer in the eyes of addiction treatment specialists, such as Dr. Andrew Kolodny, who object to full MOR agonists for chronic pain. 

Yet safety is in the eyes of the beholder.  Despite its decreased abuse potential, buprenorphine can still be abused and cause overdoses because the ceiling effect for respiratory depression does not apply universally, particularly to opioid-naïve patients and children. Buprenorphine has caused the death of at least one child from unintentional exposure. 

Buprenorphine should not be used as the first opioid prescribed for chronic pain.  Because it cannot achieve the full analgesic effects that other opioids can, there is significant risk of buprenorphine leaving pain undertreated or even untreated.  A chronic pain patient on long-term buprenorphine therapy who experiences acute or breakthrough pain may not be able to get relief by taking another opioid.  Even more disturbing is the lack of pain control in patients who need surgery, have an acute injury from trauma or an acute painful medical emergency.

Buprenorphine Injection

Recently Indivior, a spin-off of Reckitt Benckiser Pharmaceuticals (which makes Suboxone), submitted a New Drug Application to the Food and Drug Administration on a subcutaneous injection formulation of buprenorphine. 

A once-a-month injection would be a significant advance for opioid administration because it would significantly reduce the risk of diversion.  A patient could hardly be accused of giving away or selling a drug that is deposited in his body, or of taking an incorrect dose.  

For this reason alone, an opioid depot formulation for a chronic pain patient with monthly administration sounds very appealing.  It might eliminate the need for pain contracts, pill counts, urine drug testing, and other indignations chronic pain patients suffer every day.  Even if another medication was needed for breakthrough pain, and drug testing was deemed necessary, the depot formulation would provide a virtually indisputable level of medication that could serve as an "internal control" for test error.  Detecting the depot med at unexpected levels would alert the prescribing physician to the inaccuracy of the test rather than suggest misuse or abuse.

Nevertheless, buprenorphine is not the right opioid for once-a-month dosing.  In a 2015 paper, lead author Dr. Yury Khelemsky described a horrifying case that illustrates the dangers inherent in daily buprenorphine use.  In this case, a patient with a history of drug addiction who was being treated successfully with Suboxone suffered a broken neck that required emergency surgery.

During the procedure, the anesthetized patient began to move in response to surgical stimulation, i.e., due to pain.  Despite increasing the amount of two anesthetics, Propofol and Reminfentanil, the patient continued to move.  Only after receiving yet another drug (Ketamine) did the patient remain motionless during the delicate procedure.  During a subsequent back surgery following discontinuation of Suboxone and replacement with short-acting opioids, roughly half as much Propofol and Remifentanil provided adequate anesthesia without the addition of Ketamine. 

Khelemsky noted that as little as 8 mg Suboxone (one third of the daily dose the patient was receiving), blocks the activity of hydrocodone for up to five days, and recommended discontinuing buprenorphine at least 72 hours prior to elective surgery.  This is cold comfort to a patient requiring emergency surgery -- which could be anyone.  

An injectable depot formulation of buprenorphine would substantially increase the risk of severe and possibly untreatable pain in an emergency situation, since a depot, once injected, cannot simply be discontinued as a pill would be.  Indeed, surgery may be needed to remove the depot and halt continued administration, while existing amounts of long-acting buprenorphine in plasma may necessitate higher, riskier doses of anesthetic to surgically treat the acute injury -- all while risking inadequate pain treatment.

Inexplicably, the extensive prescribing information on a random sample of buprenorphine products contains no warnings to either patients or prescribers of the risk that pain relief from an acute medical condition, trauma or surgery may be inadequate, or that buprenorphine should be discontinued days or weeks before elective surgery. 

Ironically, one package insert warns that additional analgesia may be required during childbirth, yet it fails to warn of any other situation that may require analgesia, or how analgesia can be accomplished when considering the unique pharmacology of buprenorphine.  

This seems to reflect the mindset of Kolodny and others in the addiction treatment industry, who always seem to minimize the significance of even the most severe pain encountered by an individual when compared to the perceived societal consequences of addiction.  I wonder how many pain patients or addicts would choose such a long-acting opioid if they understood the possibility that their severe acute pain could not be controlled.

The FDA committee tasked with reviewing Indivior’s new drug application is taking public comments.  I urge anyone concerned about this new buprenorphine formulation, and the failure to warn of the possibility of untreatable acute pain when taking any buprenorphine product, to provide comments by clicking here.

Comments can be submitted through October 27, 2017.  If received by October 17, they will be provided to the committee, which is scheduled to meet on October 31.  Comments received after October 17 will be taken into consideration by the FDA. 

Jane Babin, PhD, is a molecular biologist and a biotechnology patent attorney in southern California.

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.

What Are the Odds of Failing a Drug Test?

By Roger Chriss, Columnist

What are the odds that a person who tests positive for an illicit drug is actually using that drug?

That is a vital question in pain management and the opioid crisis, because millions of pain patients undergo drug tests regularly and some are falsely accused of failing them. The answer is not just a matter of looking at the accuracy of the test.

In a simple situation, like a toss of a coin or a roll of a die, computing the probability of an outcome is elementary. Most people realize that a toss of a coin has an equal chance of coming up heads or tails.

But drug testing is not as simple. It is an example of conditional probability. A drug test that is 95% accurate will not find drug users 95% of the time. That is because the test is applied to both drug users and non-users. We have to use a calculation known as Bayes’ Theorem to determine the real probabilities.

Bayes’ Theorem calculates the probability of one event happening given that another event has already happened. In terms of drug testing, this means the probability that a randomly selected person who has a positive test did in fact use that drug.

To perform the calculations, we need to know two things:

1. The accuracy of the drug test
2. The “base rate” at which drug use occurs in the population at large.

The accuracy of drug tests varies widely. A 2010 study estimated that drug tests generally produce false-positive results in 5% to 10% of cases and false negatives in 10% to 15% of cases.

Data on the base rate of drug use also varies. The CDC claims as many as 25% of chronic pain patients develop signs of opioid use disorder. However, a Cochrane review found addiction in less than 2% of long-term opioid users.

This gives us four general scenarios to consider when estimating the probability that a chronic pain patient with a positive test result is actually misusing opioids:

Scenario I (25% base rate; 95% accurate drug test):  90%
Scenario II (25% base rate; 90% accurate drug test): 83%
Scenario III (2% base rate; 95% accurate drug test):  29%
Scenario IV (2% base rate; 90% accurate drug test):  17%

With a high base rate of opioid misuse and a more accurate test, the probability is high at 90 percent. On the other hand, as the base rate falls and test accuracy decreases, the probability drops significantly, down to 17 percent. This means that the probability of a person getting a false positive result increases.

The Base Rate Fallacy

Bayes’ Theorem clearly shows that the base rate of drug use has a large effect on the probability that a person will get a false test result. Because clinical decisions and healthcare policy are often based on the results of such tests, knowing the probabilities is vitally important.

The base rate fallacy occurs when a decision is made without taking the real base rate into consideration. As shown above, the upper value of 25% is more than 10 times the lower value of 2 percent, indicating a high degree of uncertainty in the base rate.

Moreover, the base rate is not the same in all locations or across all populations. Drug abuse is known to be higher in some places and among some age groups. The accuracy of drug tests also represents an average, but factors such as biochemical individuality and testing conditions may influence actual performance.

Further, drug testing is not an entirely random process. For instance, prior to prescribing opioid medication, a doctor may perform a risk assessment using an Opioid Risk Tool. A doctor may also have hints that a patient is abusing opioids to motivate testing. In either case, randomness is lost and the base rate shifts.

Conditional probability produces counter-intuitive results, with a high degree of dependence on the base rate -- itself a number that requires constant attention.

The bottom line is that drug testing alone is not foolproof. Clinical judgment by experienced physicians, combined with information such as pharmacy data, pill counts and medical records, will always get better odds than drug testing alone.

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.

Cigna Won’t Pay for OxyContin in 2018

By John Burke, Guest Columnist

A major health insurance company -- Cigna -- announced this week that they it is removing OxyContin from its list of approved medications and replacing it with another extended release oxycodone product.

“Our focus is on helping customers get the most value from their medications — this means obtaining effective pain relief while also guarding against opioid misuse," said Jon Maesner, Cigna's chief pharmacy officer.

OxyContin is the only opioid-based prescription painkiller that Cigna is removing in 2018 as "a preferred option" from its formulary, a list of medications that its health plans will pay for.

On the surface, this declaration might appear to be a great stride toward reducing prescription drug abuse. Cigna is replacing OxyContin with Collegium’s product, Xtampza ER, which is also an abuse deterrent extended release oxycodone product. 

My problem with this announcement is that OxyContin, along with the other abuse deterrent formulations (ADFs), have very little abuse issues. OxyContin certainly did up until its reformulation in August 2010, but that was over 7 years ago! Since then, there is much documentation from a variety of sources that show the diversion of OxyContin has fallen extensively.

Xtampa ER and the other abuse deterrent formulations also have little to no abuse issues since they have been on the market. 

If Cigna wants to change drugs, that’s likely a financial decision and one they should make, but please don’t tout your move as striking a blow for reducing drug diversion.

It will do nothing to reduce drug diversion, since the clear majority of diversion falls into the immediate release opioids, primarily oxycodone and hydrocodone. 

What is even more concerning to me is the vilifying of any drug that hundreds of thousands of legitimate pain patients take to live a semblance of a normal life, especially when that drug does not have a recent history of abuse and diversion. It also tends to make suspect any and all abuse deterrent products, which is deceptive at best. 

One thing the abuse deterrent formulations have done is to help narrow their focus to legitimate pain patients. Those seeking to get “high” moved to immediate release opioids or black market heroin/fentanyl combinations, not the ADF products. That’s why the FDA is now considering requiring companies that produce generic opioids to develop ADF properties for their drugs. 

No matter what Cigna declares, the bottom line is that ADF’s have been successful. They are not an end all to diversion and abuse, but they do help pain patients get easier access to pain medication. I am hoping that is everybody’s ultimate goal. 

John Burke recently retired after nearly 50 years in drug and law enforcement in southwestern Ohio.

John is a former president of the National Association of Drug Diversion Investigators and current president of the International Health Facility Diversion Association.

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represent the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.

Heroin Overdoses in ER's Surpass Rx Opioid Overdoses

By Pat Anson, Editor

The number of patients admitted and discharged from U.S. hospitals for abuse of opioid pain medication has declined significantly this decade, while the abuse of heroin and illicit fentanyl has surged, according to a new study that documents the shifting nature of the nation’s overdose crisis.

Researchers at Stanford University analyzed national trends in hospital inpatient and emergency department (ED) discharges for opioid abuse, dependence and poisoning from 1997 to 2014, the last year data was available.

They found that hospital admissions for overdoses from pain medication started falling in 2010, the same year that opioid prescriptions began declining.

At the same time, hospital discharge rates for heroin poisoning increased at an annual rate of over 31 percent. By 2014, heroin overdoses exceeded those from prescription opioids in emergency rooms by almost a 2 to 1 margin.

“After 2008, ED discharge rates for heroin poisoning increased more sharply than the rates for any opioid poisoning -- signaling that the scope of heroin harm is worse than previously suggested -- while discharges for prescription opioid poisoning recently began to decline in both the ED and inpatient settings,” researchers reported in the journal Health Affairs.

“While these changes could be the result of national and local policies aimed at reducing the prescribing of opioids, the expanded availability of heroin and new lethal illicit drugs, such as nonpharmaceutical fentanyl, could mean that they are being used instead of prescription opioids.”

The findings add evidence to recent public health concerns that people misusing or addicted to prescription opioids are switching to heroin and synthetic opioids such as fentanyl because they are cheaper and easier to get.

"This suggests that the expanded availability of lethal illicit drugs are being used to replace prescription opioids in some cases," said Tina Hernandez-Boussard, PhD, associate professor of medicine, of biomedical data sciences and of surgery at Stanford University School of Medicine.

source: health affairs

The Centers for Disease Control and Prevention has been reluctant to admit that efforts to reduce opioid prescribing could be backfiring, although their own statistics indicate otherwise.  Deaths involving heroin and synthetic opioids overtook overdoses linked to prescription opioids in 2016, the same year the CDC released its opioid prescribing guidelines.

As PNN has reported,  the CDC last week launched a public awareness campaign to combat the abuse of prescription opioids, a marketing effort driven by surveys and focus groups that completely ignores the scourge of heroin and illicit fentanyl.

“The campaign does not include messages about heroin. 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. Heroin is a related topic that also needs formative research and message testing,” the CDC explained.

The Stanford study found that discharge rates for prescription opioid poisonings declined annually by about 5 percent from 2010 to 2014, while discharge rates for heroin poisoning increased at an annual rate of 31.4 percent from 2008 to 2014. The trend has likely worsened since 2014, as heroin and illicit fentanyl are even more widely available on the black market.

"I'm cautiously optimistic that prescribing clinicians are positively reacting to the opioid crisis and therefore prescription opioids are contributing less to the overall drug epidemic," Hernandez-Boussard said. "That's the good news. The bad news is that although prescription opioid use decreased, heroin and methadone greatly increased.”

Anna Lembke, MD, an associate professor of psychiatry at Stanford and a board member of Physicians for Responsible Opioid Prescribing (PROP), says she has no doubt many people addicted to prescription opioids have switched to using heroin or illicit fentanyl.

"My patients have told me that's exactly what they did," said Lembke. "Heroin was cheaper and easier to get."

Fake Fentanyl Pills Found in 40 States

By Pat Anson, Editor

Counterfeit painkillers and fake medications made with illicit fentanyl have killed Americans in at least 16 states, according to a new report that found the highly dangerous pills have spread from coast to coast.

“We have documented the spread of counterfeit pills made with illegal fentanyl throughout 40 states. There is documentation that counterfeits made with fentanyl have killed Americans in at least 16 of those states. The other 24 states probably have deaths attributable to counterfeits made with fentanyl, but because of limited awareness of the problem, those deaths may not have been investigated for counterfeit drugs,” said the report by the Partnership for Safe Medicines (PSM) a coalition of pharmacy groups and other healthcare organizations.

The report is based on a review of court records, statements by law enforcement and public health agencies, and news reports.

Fentanyl is 50 to 100 times more potent than morphine. It is legally available in lozenges, patches and other medications to treat severe pain, but in recent years illicit fentanyl has become widely available on the black market, where it is often mixed with heroin or used in the production of counterfeit drugs.

Many addicts looking for a high or pain sufferers looking for relief have no idea what they’re buying. Experts say a single dose of fentanyl as small as two or three milligrams can be fatal.

“Up until now, it’s been difficult to grasp the scope and pervasiveness of the counterfeit drug problem,” said Dr. Marvin Shepherd, chairman of the PSM Board and former director of the Center for Pharmacoeconomic Studies at the University of Texas at Austin’s College of Pharmacy. “We’ve had a number of examples of counterfeit pill seizures and tragic fentanyl-related deaths, but this report paints a picture of a nation under siege from fake and lethal drugs coming across our borders.”

Massachusetts, Pennsylvania, New Jersey, Ohio and several states now report they have more people dying from overdoses of illicit fentanyl than from prescription opioids. 

Most of the illicit fentanyl is manufactured in China and smuggled into the U.S. by drug cartels. In August, the Mexican military found over 140 pounds of powdered fentanyl hidden inside a tractor trailer rig at a checkpoint near Yuma, Arizona. The shipment, which had an estimated street value of $1.2 billion, also included nearly 30,000 counterfeit tablets made with fentanyl.

The fake pills are often designed to look like oxycodone or the anti-anxiety drug Xanax, and are hard to distinguish from the real thing.

“They’re relatively cheap (to make) and the profit margin is phenomenal,” said Lisa McElhaney, President of the National Association of Drug Diversion Investigators, during a recent seminar for pain management providers. “You’re talking about such a miniscule amount (of fentanyl). But it has such a heavy potency and purity level that it is fatal.”

McElhaney said the black market in prescription drugs used to be dominated by legally-made medications that were stolen or diverted from medicine cabinets, pharmacies or drug manufacturers. She now believes most of the pills sold on the street are counterfeit.

counterfeit oxycodone pills

“I would say 99% of what we are seeing on the street, bought and sold, is product from China, India, Mexico, or from second or third-hand distributors. It is not pharmaceutical grade, FDA approved fentanyl,” she said.

While the DEA and other law enforcement agencies have been warning of the fentanyl problem for years, federal health officials have been slow to recognize or even address it – focusing instead on limiting the use of opioid pain medication.

For example, the Centers for Disease Control and Prevention recently launched a new marketing campaign, using videos, online advertising, billboards, newspapers and radio ads to raise awareness about the risks of prescription opioids. The campaign completely ignores the role of fentanyl and heroin in the overdose crisis, because the CDC didn't want to risk “diluting” its primary message.

“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.

Politicians are also focused on prescription opioids. Several states have adopted or are considering laws that limit opioid prescriptions for acute pain to only a few days’ supply – a move that President Trump’s opioid commission appears to be considering as a recommendation in its final report.

“This is a prevention measure… to limit the number of drugs that are out there for improper diversion and to make sure that we don’t inadvertently turn people into addicts by giving 30, 60, 90 pills the first time,” said commission chairman Gov. Chris Christie of New Jersey, whose state has adopted a five day limit on new opioid prescriptions.

This week the Pharmaceutical Research and Manufacturers of America -- an organization that represents virtually every major drug maker – told the commission that it would support a 7-day limit on opioid prescriptions for acute pain.  

Drug Makers Support 7-Day Limit on Rx Opioids

By Pat Anson, Editor

A leading organization of pharmaceutical companies announced today its support for a 7-day limit on opioid prescriptions for acute pain.  

The announcement -- made during a meeting of President Trump’s opioid commission – marks a significant shift for the industry and is likely to speed up efforts to have limits imposed nationwide on opioid medication for short-term pain.

“PhRMA is announcing for the first time our support to limit the supply of opioids to 7 days for acute pain management. Too often, individuals receive a 30-day supply of opioid medicines for minor treatments for short-term pain,” said Stephen Ubl, President and CEO of PhRMA, the Pharmaceutical Research and Manufacturers of America.  

“Overprescribing and dispensing can lead to patients taking opioids longer than necessary and excess pills falling into the wrong hands.”

PhRMA is a trade organization that represents over 3 dozen pharmaceutical companies, including AstraZeneca, Bayer, Allergan, Bristol-Myer Squibb, Eli Lilly, Johnson & Johnson, Merck, Pfizer, Teva, Novartis, GlaxoSmithKline, and Purdue Pharma.

“Our announcement is candidly an unprecedented step for the industry. We’ve always supported physician autonomy and the preservation of the physician-patient relationship, but as you know, given the scope of this (opioid) crisis,we believe this is the right thing to do,” Ubl said.

“I want to thank you and the industry for stepping forward," said commission chairman Gov. Chris Christie of New Jersey. “This is a prevention measure… to limit the number of drugs that are out there for improper diversion and to make sure that we don’t inadvertently turn people into addicts by giving 30, 60, 90 pills the first time. And so the fact that the pharmaceutical industry is willing to step up and acknowledge that there is something that needs to be done is an important first step.”

New Jersey, Ohio, New York and several other states have already implemented or are considering laws to limit the number of days opioids can be prescribed and dispensed for acute, short-term pain. This week Florida Gov. Rick Scott announced that he would support legislation for a 3-day limit on opioids for acute pain in his state. Strict conditions would have to be met to get a 7-day supply.   

A bill introduced in the U.S. Senate earlier this year would require doctors nationwide to limit the initial supply of opioids for acute pain to seven days, a prescription that could not be renewed.  The bill by Sen. John McCain and Sen. Kirsten Gillibrand was referred to the Senate Judiciary Committee in April, but has gone no further.

CVS Health announced last week that it would limit opioid medication for acute pain to 7 days in all of its pharmacies nationwide, starting February 1.

CVS will also limit opioid doses for both acute and chronic pain to 90mg morphine equivalent units, and patients would be required to try immediate release formulations before using extended release opioids.

‘Moonshot’ Needed for New Pain Treatments

Today’s meeting of President Trump’s opioid commission focused largely on expanding access to addiction treatment and developing new ways of treating chronic pain without the use of opioid medication. During the two-hour meeting, there was hardly any mention of illegal opioids or the scourge of heroin and illicit fentanyl now sweeping the country.

"Our nation needs a moonshot commitment to the development of non-opioid pain treatments. We need new therapies and we need them fast," said Jim Campbell, MD, President of Centrexion Therapeutics. "The abuse of opioids costs lives, but the other equally important issue is the problem of untreated pain. Untreated pain leads to lost work, depression, lack of sleep, social withdrawal and may even lead to suicide."

Commission member Patrick Kennedy, a former congressman in recovery from addiction, said the problems of pain, addiction, depression and suicide are all intertwined, and need better advocacy.

“Clearly, depression is rampant. The opioid crisis was driven by a depression crisis. And while we’re talking about the opioid crisis and overdose deaths, suicide is getting right up there, to the height of the AIDS epidemic itself,” said Kennedy. “Because these illnesses are so stigmatized, the advocacy is really anemic. There’s no one out there shaking the trees as if this were HIV and AIDS, like we saw in those crises.”

To watch a replay of the commission meeting, click here.

Trump Opioid Commission Delays Final Report

By Pat Anson, Editor

The chairman of President Trump’s Commission on Combating Drug Addiction and the Opioid Crisis has asked for – and apparently been granted – a one month delay in releasing the panel’s final report.

In a letter posted on the White House website, New Jersey Gov. Chris Christie said the commission’s “research and policy development are still in progress,” and that he was extending the deadline from October 1 to November 1.

Christie said the opioid commission would hold its third public hearing September 27 at the White House. A notice published in the Federal Register indicates the meeting will focus on pain management and the diversion of opioid pain medication.

“The meeting will consist of statements to the Commission from invited government, nonprofit, and business organizations regarding Innovative Pain Management and Prevention Measures for Diversion followed by discussion of the issues raised,” the statement says. No list of attendees is included.

Christie’s letter also says the opioid commission will visit an Ohio medical center to learn about “innovative pain management strategies” and will meet in New Jersey with representatives of the pharmaceutical industry “to talk about partnership opportunities with the National Institutes of Health and the Food and Drug Administration.”

Until now the focus of the opioid commission has been on treating opioid addiction. An interim report released in July recommends increased access to addiction treatment, mandatory education for prescribers on the risks and benefits of opioid medication, and increased efforts to detect and stop the flow of illicit fentanyl into the country. There are no specific recommendations aimed at reducing access to prescription opioids or providing different forms of pain management.

Bondi Joins Commission

Another possible sign of a shift in the commission’s direction is the recent appointment of Florida Attorney General Pam Bondi to the panel. Bondi is now listed as member of the commission on the White House website,  although there has been no official announcement by the Trump administration. She is the fifth politician appointed to the six member panel.

Bondi played a prominent in shutting down on Florida’s pill mills several years ago, but critics say she has been slow to acknowledge that the opioid crisis has shifted away from prescription painkillers to street drugs like heroin and illicit fentanyl. Many pain patients in Florida still have trouble finding pharmacies willing to fill their opioid prescriptions.

Bondi recently joined other state attorneys general in asking pharmaceutical companies for information about their marketing, production and distribution of opioids.

“Florida citizens continue to become addicted to opioids and die daily -- meanwhile, prescription drug manufacturers, distributors and the medical profession all point fingers at each other as the cause of this national crisis,” Bondi said in a statement. “This far-reaching multistate investigation is designed to get the answers we need as quickly as possible. The industry must do the right thing. If they do not, we are prepared to litigate.”

Bondi also recently joined the National Association of Attorneys General in asking the insurance industry to do more to reduce opioid prescriptions and combat opioid abuse.

“Insurance companies can play an important role in reducing opioid prescriptions and making it easier for patients to access other forms of pain management treatment. Indeed, simply asking providers to consider providing alternative treatments is impractical in the absence of a supporting incentive structure,” the attorneys general said in a letter to an insurance industry trade group.

“Insurance companies thus are in a position to make a very positive impact in the way that providers treat patients with chronic pain.”

In addition to Bondi and Christie, opioid commission members include Gov. Charlie Baker of Massachusetts, Gov. Roy Cooper of North Carolina, Bertha Madras, PhD, a professor of psychobiology at Harvard Medical School, and Patrick Kennedy, a former Rhode Island congressman.

The Trump administration has still not officially declared that the opioid crisis is a national emergency – something the President said he would do in August.  

Pam Bondi to Join Trump Opioid Commission

By Pat Anson, Editor

Less than three weeks before its final report is due, President Trump’s opioid commission is getting a new member --   Florida Attorney General Pam Bondi.

Bondi is a longtime supporter of the president, served as a member of his transition team, and was once rumored to be the next head of the White House Office of National Drug Control Policy. There was speculation back in March that Bondi would be named to the opioid commission, but it was not until last week that the White House confirmed it was President Trump's "intent to appoint" Bondi to the panel, which currently has five members.

Curiously, Bondi’s office blamed New Jersey Gov. Chris Christie, the chair of the opioid commission, for the six month delay in getting her on board. Both Bondi and Christie are lame ducks serving out their final months in elected office.

“The President always intended for the Attorney General to be on the Commission – however, Governor Christie choose (sic) to begin the Commission with only himself and four others,” Whitney Ray, Bondi’s spokesman, said in an email.

“The announcement (of Bondi's appointment) is protocol before the Executive Order is signed next week. The Attorney General will continue to work with President Trump, General Kelly, Kellyanne Conway and other leaders to combat the national opioid epidemic.“

Bondi's spokesman also reportedly said that the October 1 deadline for the commission to release its final report would be extended. No such announcement has been made and the White House website still doesn’t list Bondi as a commission member.

FLORIDA ATTORNEY GENERAL PAM BONDI

The Trump administration has also yet to issue an official declaration that the opioid crisis is a national emergency – something the President said he would do over a month ago.  

"The opioid crisis is an emergency, and I am saying, officially right now, it is an emergency. It's a national emergency. We're going to spend a lot of time, a lot of effort and a lot of money on the opioid crisis,” Trump said on August 10.

Bondi played a prominent in shutting down Florida’s pill mills several years ago, but critics say she has been slow to acknowledge that the opioid crisis has shifted away from prescription painkillers to heroin and illicit fentanyl.

“The problem is Bondi isn't doing enough about the heroin epidemic,” the Miami Sun Sentinel said in an editorial.  “Considering that Bondi was once touted as a potential Trump drug czar — and infamously failed to investigate Trump University after receiving a major donation from Trump — it's no surprise that she was named to the commission. But she's still living off her reputation from the pill mill crack down.

“In fact, if you Google Bondi and heroin, by far the most you'll read about is when she slammed a drug dealer for stamping Trump's name on a batch of heroin. You won't find any solutions to our crisis.”

In a recent interview with WMBB-TV, Bondi warned that drug dealers were putting heroin and illicit fentanyl into counterfeit medications.

"It's a national epidemic and it truly affects everyone, and parents need to really warn their kids, their teens, adults need to know, never take a pill from someone you don't know, even if they say it is a Tylenol, an Advil or an aspirin. Don't take anything from someone who you don't know," said Bondi.

The initial focus of Trump's opioid commission has been on educating, preventing and treating opioid addiction. An interim report released by the commission in July recommends increased access to addiction treatment, mandatory education for prescribers on the risks and benefits of opioids, and increased efforts to detect and stop the flow of illicit fentanyl into the country.

There are no specific recommendations aimed at reducing access to prescription opioids, although they could be added to the commission’s final report.

In addition to Gov. Christie, commission members include Gov. Charlie Baker of Massachusetts, Gov. Roy Cooper of North Carolina, Bertha Madras, PhD, a professor of psychobiology at Harvard Medical School, and Patrick Kennedy, a former Rhode Island congressman. No pain patients, pain management experts or practicing physicians were appointed to the panel.

Is This the Opioid of the Future?

By Pat Anson, Editor

What do you call a pain reliever that doesn't have a name yet, is not FDA approved and may not be available for years?

Nektar Therapeutics calls it the "opioid of the future."

Nektar is a research-based pharmaceutical company that has developed a new type of opioid medication that shows promise in relieving moderate to severe pain, but without the risk of abuse and addiction of traditional opioids like oxycodone or hydrocodone.

The experimental pill -- which for the time being is called NKTR-181 --  has recieved “fast track” designation  from the Food and Drug Administration, but is at least a couple of years away from full FDA approval and a commercial launch.

That hasn't stopped Nektar from promoting NKTR-181. This week it hosted a lunch symposium on the drug at PainWeek -- an industry trade show underway in Las Vegas -- a sign of just how confident the company is that NKTR-181 will receive final approval from the FDA.

"We think we could see approval as early as the end of next year," says Steve Doberstein, PhD, Chief Scientific Officer of Nektar. "So we could see a launch of this product in the first part of 2019. That would be my aspiration. If we have to do more clinical trial work, it would be delayed."

The FDA usually requires at least two "Phase 3" clinical studies to prove a new drug's effectiveness. Nektar has only completed one -- a Phase 3 study of over 600 patients with chronic back pain who reported that their pain scores dropped by an average of 65% when taking NKTR-181 twice daily.

Nektar has also completed smaller safety studies that found recreational drug users had significantly less “drug liking” of NKTR-181 -- even at high doses -- when compared oxycodone. Participants also had less daytime sleepiness and fewer withdrawal symptoms.

"NKTR-181 is quite boring as far as abuse metrics go. Boring is good. That was our goal. It doesn't appear to cause euphoria," says Doberstein.

NKTR-181 is "boring" because of its slow rate of entry into the brain's central nervous system – which significantly reduces the “high” or euphoric effect that recreational users seek. Many pain sufferers don't feel that high when taking opioid medication, they just get pain relief. But in the current regulatory and political climate, the only way a new opioid will be approved by the FDA is if it has a low or non-existent abuse potential.

"We're very focused on the fact that one of the building blocks of solving this problem is going to be a safe pain medication for chronic pain patients to take," Doberstein told PNN. "The things that work best are opioids. But the existing conventional old-fashioned opioids -- oxycodone is 100 years old -- come with an unacceptable side effect profile for many patients. And we think we've made something that is legitimately better. It's the first time in a very long time that a new opioid molecule has been developed."  

Doberstein thinks NKTR-181 has such low potential for abuse that it will not need to come in an abuse deterrent formula that would make it harder to crush or liquefy. The FDA could still require one, however, which would delay the drug's commercialization even longer. The agency is currently reviewing the effectiveness of all drugs with abuse deterrent formulas.

The FDA also has a new opioid policy steering committee that is examining whether the agency sufficiently considers the risk of abuse during its evaluation of new opioids.  That could result in rule changes that Nektar would have to address. Anti-opioid activists and politicians could also pressure the FDA to require more clinical studies on the safety and potential abuse of NKTR-181.

Another potential obstacle is that Nektar still needs to partner with a larger pharmaceutical company to help produce and commercialize NKTR-181 -- which is when the no-name "opioid of the future" will likely get a makeover with a branded name to make it more marketable.

"This is the kind of medicine that we think could be quite significant. It could really change medical practice. That means we need a lot of education, and a lot of outreach to physicians, hospitals, payers, patient advocates and law enforcement. We have a lot to do. And its probably beyond us to do it ourselves. So we'll have a commercialization partner of some kind," said Doberstein, who told PNN he expects Nektar to announce its new partnership by the end of the year.

How Fish Got Hooked on Hydrocodone

By Pat Anson, Editor

We hear it all the time from PNN readers. They don’t trust academic research about opioids and addiction, and feel much of it is biased or just plain fishy.

You can certainly say the latter about a new study by researchers at the University of Utah.

They devised a system that allows zebrafish, a small tropical fish popular in home aquariums, to self-administer doses of the painkiller hydrocodone. In less than a week, researchers say the fish were hooked on hydrocodone and showed signs of drug-seeking behavior and withdrawal.

"We didn't know if zebrafish would be a relevant model for opioid addiction, much less self-administer the drug," said Randall Peterson, PhD, a professor of Pharmacology and Toxicology, and senior author of the study published in the journal Behavioral Brain Research.

"What is exciting about this work is that we see many of the hallmarks of addiction in zebrafish. This could be a useful and powerful model."

How is this useful and how does it relate to people?

Zebrafish have more in common with people than you might think. They have 70 percent of the genes that humans have, including similar biological pathways that can lead to addiction. Like people, zebrafish have a μ-opioid receptor and two neurotransmitters, dopamine and glutamate, that trigger the natural reward system in the brain.

"Drugs of abuse target the pathways of the pleasure centers very effectively," said first author Gabriel Bossé, PhD. "These pathways are conserved in zebrafish, and the fish can experience some of the same signs of addiction and withdrawal as people."

Bossé and Peterson tested their system in a tank with a food dispenser equipped with a motion detector that the fish could trigger by swimming nearby. It didn’t take long for the zebrafish to learn how to get food.

Then the researchers removed the food dispenser and replaced it with one that injected small doses of hydrocodone into the water when a fish swam nearby. A continuous flow of water flushed the tank, which forced the fish to trigger the dispenser to receive another dose of hydrocodone.

Over the course of five days, the fish learned how to self-administer the drug. You can watch a demonstration below:

"The fish needed to perform an action to get the drug rather than receiving it passively," said Bossé. "Drug-seeking has been modeled before in rodents and primates, but having a model to study this in zebrafish could move the [study of addiction] forward."

The drug-seeking behavior increased when the zebrafish were forced to receive the opioid in progressively shallower water, a stressful environment that unconditioned fish would normally avoid.

"This was important, because we forced the fish to do more work to receive the drug, and they were more than willing to do more work," said Peterson.

The researchers took their experiment a step further by exposing the conditioned fish to naloxone, a drug used to treat overdoses that blocks opioid receptors. Sure enough, naloxone appeared to reduce the fish’s drug-seeking behavior.

The researchers believe their zebrafish model can lead to new drug therapies, because it can be used to rapidly test thousands of different chemical compounds. They also believe the genetic make-up of zebrafish can be altered to explore the specific biological pathways associated with addiction.

Zebrafish do have other qualities humans can learn from. Researchers at Duke University are studying proteins that enable a zebrafish to completely heal its spine -- even after it was severed. They hope this knowledge will someday lead to new therapies to repair damaged spinal cords in humans.

Trump Declares Opioid Crisis National Emergency

By Pat Anson, Editor

President Donald Trump said he would declare the opioid crisis a national emergency, just two days after his administration said a declaration wasn’t necessary.

"The opioid crisis is an emergency, and I am saying, officially right now, it is an emergency. It's a national emergency. We're going to spend a lot of time, a lot of effort and a lot of money on the opioid crisis,” Trump said outside the clubhouse of his golf course in Bedminster, New Jersey.  “We’re going to draw it up and we’re going to make it a national emergency. It is a serious problem the likes of which we have never had.”

In a brief statement after the President’s remarks, the White House said Trump had instructed the administration “to use all appropriate emergency and other authorities to respond to the crisis caused by the opioid epidemic.”

An estimated 142 Americans are dying every day from drug overdoses of all kinds, not just opioids. Prescription painkillers are often blamed as the cause of the problem, although deaths linked to opioid medication have leveled off in recent years. Heroin and illicit fentanyl are currently driving the overdose crisis and in some states are involved in over half of the overdose deaths.  

A White House commission last week urged the president to declare a national emergency, but administration officials indicated as recently as Tuesday that such a declaration wasn’t necessary because the administration was already treating the opioid crisis as an emergency.

“We believe at this point that the resources that we need or the focus that we need to bring to bear to the opioid crisis at this point can be addressed without the declaration of an emergency, although all things are on the table for the president,” said Health and Human Services Secretary Tom Price.

New Jersey Gov. Chris Christie, who chairs the opioid commission, applauded the apparent change of heart.

“It is a national emergency and the President has confirmed that through his words and actions today, and he deserves great credit for doing so. As I have said before, I am completely confident that the President will address this problem aggressively and do all he can to alleviate the suffering and loss of scores of families in every corner of our country,” Christie said in a statement.

“This declaration is only one of many steps we must take on the federal level to reduce the death toll and help people achieve long-term recovery – but it’s a start. I’m committed to working with the President and my fellow commissioners to end the opioid overdose epidemic,” said commission member and former congressman Patrick Kennedy.

It was not immediately clear what steps the administration will take now that an emergency has been declared. A 10-page interim report released by the opioid commission recommends increased access to addiction treatment, mandatory education for prescribers on the risks and benefits of opioids, and increased efforts to detect and stop the flow of illicit fentanyl into the country.

There are no specific recommendations aimed at reducing access to prescription opioids, although they could be added to the commission’s final report, which is due in October. Prescriptions for opioid medication – long a target of addiction treatment and anti-opioid activists – have been in decline for several years. The DEA has plans to reduce the supply of many painkillers even more in 2018.

Other measures recommended by the commission:

• Grant waivers to states to eliminate barriers to mental health and addiction treatment
• Increase availability of naloxone as an emergency treatment for opioid overdoses
• Amend the Controlled Substance Act to require additional training in pain management for all prescribers
• Prioritize funding to Homeland Security, FBI and DEA to quickly develop fentanyl detection sensors
• Stop the flow of synthetic opioids through the U.S. Postal Service
• Enhance the sharing of data between prescription drug monitoring programs (PDMPs)

No estimate was provided on the cost of any of these measures.

In a statement on Tuesday, President Trump suggested that law enforcement and abstinence should be used to address the opioid crisis. 

“The best way to prevent drug addiction and overdose is to prevent people from abusing drugs in the first place. If they don’t start, they won't have a problem.  If they do start, it's awfully tough to get off," Trump said, according to a White House transcript.