Emergency Departments Can Help Prevent Opioid Overdoses

From the Blog of Dr. Nora Volkow
Executive Director, National Institute on Drug Abuse

Additional Writings by Steven Barto, B.S., Psych.

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Originally Posted at the NIDA Website on August 26, 2019

One of the biggest risk factors for overdose death from opioids is having had a previous overdose. Common sense and a growing body of research suggest that patients with Opioid Use Disorder who receive acute care in an emergency department will be at reduced risk for later overdose if they are initiated on medications to treat their Opioid Use Disorder. Unfortunately, too few Emergency Departments are making this a standard practice, and lives are being lost as a result.

According to a new report published by the Delaware Drug Overdose Fatality Review Commission, half of the people in the state of Delaware who died of an overdose in the second half of 2018 had suffered a previous nonfatal overdose, and more than half (52%) of the overdose deaths occurred within three months of a visit to the emergency room. Even when visits were not for overdose, signs of Opioid Use Disorder were apparent during the visit in most cases. The report thus recommended that patients who visit emergency rooms with obvious signs of Opioid Use Disorder should be immediately referred to rehabilitation treatment. Optimally, the initiation of medication for Opioid Use Disorder should be started before patients are discharged. This will improve their clinical outcomes.

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Even without a waiver, Emergency Department providers are permitted to administer Subcutex (buprenorphine) or methadone a limited number of times to patients under their care. In fact, several studies have now shown the benefit of initiating Subcutex in the Emergency Department rather than just referring the patient to drug treatment—it is called an “emergency” department for a reason! A recent NIDA-funded study by Yale researchers published in JAMA in 2015 showed that Subcutex treatment initiated by Emergency Department physicians was associated with decreased opioid use and improved treatment engagement in the 30-day period following discharge.

There is significant evidence that medications for Opioid Use Disorder prevent overdoses. For example, a prospective cohort study of 17,568 opioid overdose survivors in Massachusetts published last year in Annals of Internal Medicine found significant reductions in the risk of subsequent overdoses over the next 12 months in those who received treatment with methadone or Subcutex. Yet, only 30 percent of those who had overdosed received medication for Opioid Use Disorder. This statistic is extremely alarming, because the sample of patients was clearly at high risk for overdosing.

Bottles of Opiate Prescriptions

More alarmingly, 34 percent of those who had been treated for overdose received additional opioid pain prescriptions during the subsequent 12 months, despite their overdose history, and 26 percent received benzodiazepines, which as respiratory depressants further increase risk of overdose in those who misuse opioid drugs or who are being treated with high doses of opioid medications for pain management. [From my personal experience, benzodiazepines were hightly addictive and I tended to abuse them along with oxycodone. Family members noted my complete lack of sadness or empathy during my father’s funeral in December 2014. I stared at the floor and did not shed a tear. This is solely based on the fact that I was high on oxycodone and benzodiazepines at that time.]

It is crucial that acute care physicians, and the health care systems in which they practice, become aware of the importance of ensuring that patients be screened for Opioid Use Disorder and, if same is detected, that they receive treatment, ideally by initiating them on Subcutex before they are released.  Additionally, patients who visit an Emergency Department because of an overdose, or who otherwise show signs of Opioid Use Disorder, should be sent home with Narcan (naloxone)  and given instructions on how to use it to reverse an opioid-induced overdose. This was another recommendation of the Delaware report.

Naloxone kit

Four out of five fatal overdoses reviewed by the Delaware state commission occurred in a private residence were Narcan was unavailable in nearly 93% of the cases. Abundant research has shown the life-saving benefits of distributing Narcan not only to people who are addicted to opioids or misusing them but also to pain patients being treated with high doses of opioid medications and their families and friends. After all, patients taking opiates for severe chronic pain are at risk of becoming dependent on the narcotic, and could suffer an accidental opiate overdose. It is simply a matter of brain neurochemistry that has no true moral component, and can impact patients of any socioeconomic class.

Making Emergency Department physicians more responsive to the opioid epidemic often means educating colleagues and changing hospital culture. Many emergency physicians do not feel adequately prepared to treat with Subcutex—there are real or perceived logistical impediments like obtaining prior authorization from insurers. Emergency physicians should be encouraged to complete the training necessary to get a waiver to prescribe Subcutext, which greatly enhances their confidence and ability to respond to patients with Opioid Use Disorder.

The NIDA-MED website includes firsthand stories from physicians implementing emergency department overdose treatment with buphrenorphine and prescribed Suboxone to patients suffering from Opioid Use Disorder. Gail D’Onofrio, the lead researcher of the 2015 JAMA study, translated the study findings into practical videos for Emergency Room clinicians now posted on NIDA-MED. NIDA has also developed a companion, comprehensive set of resources to help emergency physicians initiate buprenorphine. In fact, initiating buprenorphine treatment in the emergency room includes step-by-step guidance on buprenorphine treatment, discharge instructions, instructional videos for clinicians on interacting with Opioid Use Disorder patients, and other useful materials.

[PLEASE NOTE: I have added the following sections to Dr. Volkow’s blog post.

Let’s Take a Look at Opioid Use Disorder

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The American Psychiatric Association¹ included a comprehensive explanation of Opioid Use Disorder in their Diagnostic and Statistical Manual of Mental Disorders, Fifth Ed. (DSM-5), beginning at page 541. Essentially, Opioid Use Disorder (OUD) is a problematic pattern of opioid use leading to clinically-significant impairment or distress, as manifested by at least two of the following, occurring within a 12-month period:

  1. Opioids are often taken in larger amounts or over a longer period than was intended [by the prescribing physician].
  2. There is a persistent desire or unsuccessful effort to cut down or control opioid use.
  3. A great deal of time is spent in activities necessary to obtain the opioid, use the opioid, or recover from its effects.
  4. Craving or a strong desire or urge to use opioids.
  5. Recurrent opioid use resulting in a failure to fulfill major role obligations at work, school, or home.
  6. Continued opioid use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of opioids.
  7. Important social, occupational, or recreational activities are given up or reduced because of opioid use.
  8. Recurrent opioid use in situations in which it is physically hazardous.
  9. Continued opioid use despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the substance.
  10. Tolerance, as defined by either of the following: (a) a need for markedly increased amounts of opioids to achieve intoxication or desired effect; (b) a markedly diminished effect with continued use of the same amount of an opioid. NOTE: This criterion is not considered to be met for those taking opioids solely under appropriate medical supervision.
  11. Withdrawal, as manifested by either of the following: (a) the characteristic opioid withdrawal syndrome (refer to Criteria A and B of the criteria set for opioid withdraw in the DMS-5, p. 547-548; (b) opioids (or a closely-related substance) are taken to relieve or avoid withdrawal symptoms. NOTE: This criterion is not considered to be met for those individuals taking opioids solely under appropriate medical supervision.

Healthcare is not yet doing enough to avail itself of an effective referral system in the opioid crisis: using visits to emergency rooms to get patients with Opioid Use Disrder on medication and provide them with Naloxone. Intervening in these simple ways would greatly help reduce the shocking numbers of deaths from opioids in this country.

Are You Struggling?

I was obsessed with alcohol and drugs for nearly four decades of my life, which caused horrific and lasting consequences. I ended up serving three years in a state prison around the time I turned 20 years old. My history of using had started in early summer of 1977 shortly after graduating high school. I enjoyed the escape these mind-altering (numbing?) substances provided. Admittedly, it was quite fun at first. Within months, I became dependent on drugs and alcohol in order to function and to feel any degree of release from the demons of my past and the obsessive thoughts in my brain. I couldn’t laugh, relax, enjoy sex or food, or sleep unless I first got high or drunk. Sadly, I struggled with active addiction from shortly after my 18th birthday in 1977 to June 8, 2019.

I had started smoking cannabis and popping oxycodone pills during early Spring of 2018 in an attempt to self-medicate my depression, anxiety, and severe back pain secondary to a construction-related injury several years ago. Looking at the above description of Opioid Use Disorder established by the DSM-5, when in active opiate addiction I exhibit ten out of eleven of the criteria needed for a definitive diagnosis! I am sixty years old now, and I am finally looking at who I am in Christ. I am clean from opiates and cannabis for nearly 120 days, and I no longer dwell on the decades of constant failure. I should mention that I nearly took my own life several times during  my long history of active addiction. My struggle with opiates is fairly recent, and has taken me to places that I did not wish to go. Thankfully, I am confronting this issue with confidence in the power of the Name of Jesus and my unmitigated committment to change, never to be the same.

I work extensively today with a drug and alcohol counselor who is a believer in Christ. The ability to focus on Christ in therapy sessions provides an opportunity to examine the “spiritual malady” of addiction. I am constantly in contact with several elders at my home church who have become mentors. I am “coachable” today. I have started speaking regularly with Duche Bradley on the phone. He has a nationwide ministry of speaking in prisons and high schools about addiction and who we are in Christ Jesus. You can hear his “white chair” testimony here. He has led me through renouncing pharmacia and all nature of flesh-bound habits and addictions, and has encouraged my growth in Christ in order to move forward with my own ministry. Duche said to me, “Brother, if you do these things, you will be blown away about the many permanent changes in your character and your life.”

Nowadays, after having submited to Jesus Christ as my “higher power”—indeed, as my Savior and my Lord and Teacher—the obsession to use chemicals is gone. Likewise, the physical compulsion or craving has been defeated. I could never accomplish this under my own power. The Big Book of Alcoholics Anonymous tells us that alcohol is cunning, baffling, and powerful! No human power can relieve our alcoholism, but God can and will if we seek Him. The same applies to drug addiction. After all, a drug is a drug whether you drink it, snort it, or shoot it into your veins.

It is only through admitting my weaknesses and deciding to work with those who have risen above the evil and failure in their lives that I can get on with my life: studying theology on the master’s degree level, teaching weekly Bible study lessons at a local homeless shelter, and reaching out to newcomers at 12-Step meetings that are presently on a rapid decent into the living hell of active addiction. By accepting God’s “call” on my life, I can move toward a ministry of evangelism, applied apologetics, and lecturing, writing about, and teaching about Christianity and the release we all can have through Jesus. This is my life (as it was always meant to be), and I am happy to finally get on with living it!

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Given the near impossibility of quitting a mind-altering substance on your own, I highly suggest you reach out to someone who’s been there. Check your local government phone number pages in the phone book or, better, yet, do a Google search for A.A. or N.A. If, however, you are in the middle of a psychological or physical life-threatening crisis secondary to substance abuse, Please Call 911.

With suicides on the rise, the federal government wants to make the National Crisis Hotline easier and quicker to use. A proposed three-digit number — 988 — could replace the National Suicide Prevention Lifeline, 1-800-273-TALK (8255). The FCC presented the idea to Congress in a report earlier this month and is expected to release more information and seek public comment about the proposal in the coming months. PLEASE REMEMBER: You are not alone.

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¹ American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, fifth ed. (DSM-5). Arlington, VA: American Psychiatric Publishing (2013), pp. 547-548.

Scientific Findings and Achievements in Drug Abuse Research for 2018

From the Blog of Dr. Nora Volkow, Director
National Institute on Drug Abuse
January 7, 2019

Dr. Volkow noted, “As we enter 2019, it is a good time to take stock of what NIDA accomplished over the past year. As always when I look back at the research being done by NIDA grantees and partners, I am amazed at the wealth of knowledge being created from our investments. Here I want to highlight just a few of the many outstanding developments in basic science, new therapeutics, and epidemiology and prevention research from the year that just ended.”

Basic Science Advances

Recent years have seen major advances in the understanding of receptor functioning. In March 2018, a team of researchers at NIDA’s Intramural Research Program (IRP) reported in Nature Communications on an advance in understanding G protein-coupled receptors (GCPRs), a large family of receptors that play an important role in the brain’s response to drugs. These receptors often assemble into larger complexes, but it has been unknown whether those complexes are merely the product of random collision between signaling molecules as they move across the membrane or whether they pre-form into complexes that serve specific functions.

The IRP team found that two common GCPRs in the reward pathway, adenosine A2A and dopamine D2 receptors (along with their G proteins and target enzyme), assemble into preformed macromolecular complexes that act as computation devices processing incoming information and enabling the cell to change its function based on that information. This knowledge could facilitate the development of more precise medication targets.

In June 2018, a team of NIDA-funded researchers at the University of California–San Francisco, along with colleagues in Belgium and Canada, reported in Neuron magazine that they had developed a genetically-encoded biosensor that can detect activation of opioid receptors and map the differences in activation within living cells produced by different opioids. The fact that opioids bind to receptors on structures within the cell—and not just on the cell membrane—was itself a novel finding, but the team also discovered striking differences in how endogenous versus synthetic opioids interact with these structures.

While endogenous peptides activated receptors on membrane-bound compartments within the cell called endosomes, synthetic opioid drugs activated receptor sites on a separate structure called the Golgi apparatus (which acts as a hub for routing proteins to various destinations in the cell). These very different patterns of activation within the cell may lead to greater understanding of why non-peptide opioid drugs produce tolerance as well as the behavioral distortions seen with opioid misuse and addiction whereas the body’s endogenous opioid peptides do not.

The same month, a team led by neuroscientists at UCLA studying narcolepsy reported research in Science Translational Medicine based on their discovery that postmortem brains from individuals who had been addicted to heroin show greatly increased numbers of neurons producing the neuropeptide hypocretin. Hypocretin helps regulate wakefulness and appetite, and a diminished number of cells in the brain producing it is associated with narcolepsy. The researchers went on to conduct a study administering morphine to mice, which as observed in the postmortem study produced increased numbers of hypocretin neurons. The results suggest that increases in these cells and in brain hypocretin could underlie the complaints of sleep problems in patients with an opioid use disorder (OUD). Since insomnia is a factor that contributes to drug taking in OUD and other addictions, strategies to counteract hypocretin signaling might have therapeutic benefits.

Prevention and Treatment

Last year, NIDA-funded research resulted in new therapeutics and apps for opioid use disorder. In May, the FDA approved lofexidine, the first medication approved to treat physical symptoms of opioid withdrawal. In December, the FDA cleared the first mobile health app intended to help retain patients with OUD in treatment, called reSET-O. It uses interactive lessons to deliver a community reinforcement approach therapy and enables users to report cravings and triggers to their health care provider between office visits, along with whether or not they have used Suboxone. NIDA funded the clinical trial that led to this app’s approval. A version called reSET was approved in 2017 to help with behavioral treatment of several non-opioid substance use disorders.

NIDA-funded research in epidemiology and prevention also added greatly to the knowledge of new drug trends in 2018. Last month’s striking findings on monitoringthefuture.org alerted us to escalating use of vaping devices among adolescents. Although most adolescents in 2017 claimed they used vaping devices only to vape flavors, this year most reported they used them to vape nicotine. Alarmingly, there was also an increase in vaping of cannabis.

Several other studies published in 2018 increased our understanding of factors that may lead youth to experiment with vaping. For example, a longitudinal cohort study by researchers at Yale and reported in Addictive Behavior found that exposure to ads for e-cigarettes on social media sites like Facebook significantly increased the likelihood of subsequent e-cigarette use among middle and high school students in Connecticut. In another study published in Preventive Medicine, the researchers also found that higher socioeconomic status was associated with greater exposure to e-cigarette advertising (which in turn was associated with increased likelihood of use)—important data that can help with targeting prevention efforts. Other work by UCSF researchers and published in Pediatrics found that e-cigarette use in adolescents was positively associated with being a smoker of conventional cigarettes, lending further support to the view that these devices are not diverting youth from smoking cigarettes but may be having the opposite effect in some users.

Looking To The Future

This year the Adolescent Brain Cognitive Development (ABCD) Study successfully completed recruitment of 11,874 participants, ages 9-10, who will be followed for 10 years, through young adulthood. The study, which is being conducted at 21 research sites around the country, is using neuroimaging to assess each individual’s brain development while also tracking cognitive, behavioral, social, and environmental factors (including exposure to social media) that may affect brain development and other health outcomes. The first release of anonymized data was made available so that both ABCD and non-ABCD researchers can take advantage of this rich source of information to help answer novel questions and pursue their own research interests.  Last year alone, the data resulted in more than 20 publications.

 

How Heroin Kills

The following information appeared in The Sunday Item, April 3, 2016, Sunbury, Pennsylvania.

Teresa Stoker gently pulls a sterling silver necklace from beneath the neck of her gray sweatshirt and holds it out beyond her chin. Ashes of 27-year-old Mark Stoker are piled inside a tiny cylinder, strung next to an imprint of her youngest son’s right thumbprint. His two siblings keep their brother’s ashes in keepsake key chains. Their mother has one of those, too. Mark died February 4, 2016 of a heroin overdose inside a New Columbia motel – one of 13 tri-county residents dead or suspected to have died of a drug overdose in 2016, according to coroners from Northumberland, Snyder and Union counties.

Mark was alone when motel staff found him after he failed to check out of his room. He was alone the day before, overdosed again in heroin and dumped by an acquaintance in the parking lot of a Burger King in Williamsport, PA, rain pouring onto his unconscious body, until passersby came to his aid and dialed 9-1-1.

He was supposed to be at his mother’s home in Shamokin Dam that day. They were supposed to have dinner and watch TV together. That had been the routine for days. He had stayed off heroin for six months, but he was growing irritable. His suboxone prescription was running short. He didn’t have consistent rides to counseling. He tried to make it work. He sliced the medicated film in half. As his supply dwindled, he sliced it in fours.

When Teresa pulled into her driveway on February 3rd, she could see through the blinds hung in the front window. “I knew he wasn’t in there,” she says.

Two months after his death, Mark’s family is left to reconcile love and pain, guilt and forgiveness – within themselves and within their own relationships fractured by a loved one’s fatal drug addiction. “He was the link that brought us together, and he was the one that pulled us apart,” says his sister and eldest sibling, Desiree. “He wasn’t long for this world,” adds Teresa. “He fought this to the very end,” says his brother Matt. “Mark didn’t really have a choice.”

The Stoker kids’ father died early in their lives. Mark was only 2 years old. Matt wonders if it was the impetus for mental health issues Mark would develop in life, particularly depression. Anxiety and depression are often evident in the psyche of a drug addict, according to the National Institute on Drug Awareness. “Addiction is a mental health issue,” says Dr. Rachael Levine, Pennsylvania’s physician general, who is among the officials at the forefront in addressing the Keystone State’s heroin and opioid addiction crisis. “It is not a moral failing.”

Mark sought help, and sometimes he sought it himself. He was no stranger to rehab. He’d been in and out of treatment several times, both in Pennsylvania and elsewhere. His family stood by his side the best they could, the only way they knew how. They encouraged him to lead a clean life, showed pride when he landed new jobs, sat bedside when he was hospitalized for an overdose. “Sometimes I look back and think we were fooling ourselves,” Matt says.

Matt and Desiree were the academics in the family. The former is enrolled in the physician assistant program at Pennsylvania College of Technology, and the latter is a registered nurse at Geisinger Medical Center in Danville, PA. Mark was no fool, either. His mind was for mechanics. He once rebuilt his own motorcycle after he wrecked it. Then he sold it and traded up for a better ride. His career path was in electrical work. On one job, he was hanging by a harness from a helicopter 200 feet above the ground repairing high-voltage lines. His family describes him as witty and charming, kind and sensitive, resilient and rebellious.

A quick learner, fearless in life’s pursuit, Mark hit dirt bike jumps taller than himself before he was a teen. He took quickly to Black Diamond slopes when he began to ski and bagged an eight-point buck on his first hunt. He was just 10 when he picked up on how to drive a stick shift. Accidents along the way created a need for pain relief. It’s very important to note that the American Society of Addiction Medicine found 4 in 5 new heroin users started by abusing prescription painkillers. Count Mark among the 80 percent. According to Mark’s mother, he was given pain meds at 14 when he had a wisdom tooth extracted. He took painkillers at 16 after having his gallbladder removed. Again, he took narcotic pain medication at 18 after being involved in a motorcycle accident.

Mark was 23 in 2012 when he developed painful kidney stones. His behavior suddenly changed. He became withdrawn, choosing to spend more time than normal alone in his bedroom. He was in legitimate need of relief from pain, but looking back, this is when his family says they first recognized signs of addiction. He’d been abusing oxycodone he was getting from three separate doctors. Maybe he needed relief the next summer when he stole Vicodin from his mother’s medicine cabinet.

It was September of that same year when Mark’s family first saw him experience a heroin overdose. He had borrowed his sister’s car. She found him slumped over in the driver’s seat as the engine idled – eyes glazed, sweat pooled in a cup holder. Mark’s sister dialed some of his recent calls on his cell phone. Someone told her, “He might be doing heroin.” She flipped out. The pock marks on the back of Mark’s hands weren’t bug bites as she thought on first glance. They were injection sites.

There would be more overdoses for Mark between September 2013 and the night he died in February 2016. Once his mother got a call from a Virginia state trooper. Mark overdosed in a hotel room while he was out of state on a job. Another time he was dumped at the doors of Evangelical Community Hospital in Lewisburg, PA, “dead on arrival,” as Teresa says. Attempts at recovery followed. Twenty-eight days at a Virginia facility didn’t take. The Stokers were more hopeful after a 28-day stay at Father Martin’s Ashley in Maryland, but again it didn’t help. He walked out of a rehab in White Deer, PA one week after he checked himself in.

Jobs, friendships, girlfriends – all lost by Mark to addiction, an addiction that strained an already complicated relationship, and ultimately led to his loss of parental rights to his daughter. He spoke often about the little girl, wrote about her in his journal. Teresa holds dear the few photographs she has of the two together.

A study on addiction by the Center for Rural Pennsylvania determined only 1 in 8 Pennsylvanians can afford treatment services. Geisinger Health System’s latest needs assessment says lack of insurance, cost of care, and transportation are barriers to treatment. More importantly, there simply aren’t enough providers to meet demand.

Mark had health insurance through the Health Insurance Marketplace. His mother says it didn’t cover the $150 monthly cost for suboxone, or the $100 cost per session for addictions counseling. His mother was in counseling herself, and with Mark out of work, she was covering all the bills. “We all knew he should be on [suboxone]…but we couldn’t afford it,” Teresa says.

And so the afternoon of February 4th, one day after Mark’s life was saved after he was found in the parking lot of the fast-food restaurant, came a familiar phone call to Teresa. One the whole family expected and equally feared. It was the state police. They didn’t tell her, but she knew. This time, Mark was dead.