> Pain Management and Opiod Use Disorders in the COVID Era

Pain Management and Opiod Use Disorders in the COVID Era

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Non-medical Opioid use and OUD in Adolescents

SHARON LEVY: My name is Sharon Levy. I’m the director of the adolescent substance use and addiction program at Boston Children’s Hospital, and we’re going to talk today about non-medical opioid use and opioid use disorders in adolescents. This is a picture that reminds us of the difference between opiates, which are naturally occurring or semisynthetic molecules such as opium and heroin, and opioids, which are synthetic molecules used as pain medication. While they are structurally distinct, both opiates and opioids bind to the mu opioid receptors in the central nervous system and have the same physiologic effects.

This is a schematic of the brain with arrows pointing out areas that are rich in opioid receptors. Opioid binding in the spinal cord is responsible for the remarkable pain relief associated with opioid use. These receptors seem to be most functionally available after tissue injury, and patients who have had major trauma can tolerate big doses of opioids without having much of the other effects associated with their use.

The limbic system houses the brain’s pleasure and reward center, and binding in this part of the brain results in the euphoria associated with opioid use. Binding in this area is also associated with the loss of control over opioid use that is the hallmark of addiction. Binding in the brain stem results in decreased respiration associated with overdose. The prefrontal cortex, which is the seat of executive functioning, is also rich in opioid receptors.

The body makes natural opioids called endorphins, and these molecules play an important role in homeostasis. This is a schematic demonstrating what happens when the brain is repeatedly exposed to exogenous opioids. Cells become less responsive to opioids, in this drawing, by increasing the number of opioid receptors and requiring more binding in order to trigger the cell to fire. This is responsible for the phenomenon known as tolerance.

If the exogenous opioids are withdrawn, the system is knocked out of balance. This is responsible for the withdrawal that patients experience, and also the extended period of dysphoria, cravings, and not feeling right that people with opioid use disorder often experience with abstinence. For this reason, medication is the primary recommended treatment for patients with opioid use disorders.

Changing gears for a moment, I’d like to talk about previous opioid epidemics in US history. They go back at least as far as the first European settlers. In the 1860s, there was a tremendous opioid epidemic that was enabled by the invention of the hypodermic needle around the time of the Civil War. Physicians were treating injured soldiers with morphine, and also civilians, leading to a massive opioid epidemic that resulted in Congress ultimately passing the Harrison Drug Act that strongly discouraged any opioid prescribing.

Rates of opioid addiction plummeted and remained low for about 60 years until the Vietnam War when many soldiers became addicted to easily available morphine and heroin. And heroin use also became popular among members of the countercultural movement back at home. The US Government was so worried about reintegrating addicted soldiers back into the population, that the Nixon administration passed laws allowing methadone, which by then had been shown to be an effective treatment for opioid use disorder, as a treatment.

This was a tremendous step forward for the embryonic field of Addiction Medicine. Note though, that while medication treatment signaled that addiction is a medical condition, opioid addiction was, and is, the one single condition for which treatment exists in a parallel system of methadone clinics, rather than integrated into medical practice. Things stayed relatively stable for about 25 years. In the late 1990s, the pharmaceutical industry developed and promoted powerful and easy to use oral opioid medications, marketing them as the solution to the problem of chronic pain.

That created a tinderbox, and in 1999 the Institute of Medicine threw in a match by declaring pain to be the fifth vital sign. Opioid prescribing skyrocketed, and so did opioid addiction. In 2000 Congress passed the drug abuse Treatment Act, or DATA 2000, formerly allowing the treatment of opioid use disorder with an opioid agonist known as buprenorphine. Finally, we had a medication that could be prescribed from a general medical setting.

The tremendous flood of prescribing that occurred in the 2000s led to a reservoir of opioid medication spread throughout medicine cabinets all across the country. And this is a big problem for adolescents, because teenagers are developmentally vulnerable to drug use. I will make this argument in the next few slides. This is an old slide that shows brain weight by age. I have highlighted age 10 to 12 because that is the point at which brain weight reaches its adult size. And for a long time, 13 to 14 was considered the age of majority.

The concept of adolescence as a unique developmental stage is relatively modern, not more than 100 years old. I typed the word adolescent into Google image and made a montage of the pictures that came up on the first page. The point here is that even by quick glance, we can see that adolescents are somehow different from other adults. It’s striking to me that for most of human history we did not recognize that. We also now know that brain development continues until the mid 20s.

The pictures on this slide are brain slices taken from individuals at different ages. At birth, there are few cells and few connections between them. Then, the brain blossoms through tremendous growth into a dense tangle of tissue. The final step involves pruning away unused connections while the ones that remain grow bigger and get wrapped in myelin, which is a fatty insulating tissue. These last changes speed the rate of electrical signal conduction.

So while young children are great at learning new things like speaking a language or playing an instrument, because their brains are perfectly configured for learning, adults are more proficient at these tasks because their brains support faster signaling. These ages always happen in the same order, but they happen in different parts of the brain at different ages. This slide shows immature brain in red and green, and fully myelinated brain in blue. The order of maturation is, generally speaking, from back to front. Note that even at age 20, there is still plenty of immature brain. This process is thought to be complete in the mid 20s in most people.

It turns out that brain maturation correlates with the behaviors of children we expect to see at different developmental stages. For example, in the first year or two of life, the cerebellum, which controls gross motor movements, is developing rapidly, just at the time when young children are learning to walk. And anyone who has been around a toddler knows that they are completely invested in getting up and walking, creating the practice necessary for the feedback loop that will result in brain development.

In the preschool years, the amygdala, which is involved in emotional regulation, is an area of rapid development. During this stage of life, sometimes referred to as the terrible twos, 0000 children have temper tantrums that seem to be unprovoked and also seem to resolve without intervention. These should be coming to an end by the end of this period, right as children are entering kindergarten.

During the school age years, the nucleus accumbens is undergoing rapid development, and this is the time in life when children learn to differentiate between rewards, and develop goal directed behavior. The last part of the brain to develop is the prefrontal cortex, which is the seat of executive functions, or the things that help us make good decisions like self-monitoring, error correction, and impulse control. Adolescents can, of course, make good decisions, but during this phase while their brain is still developing, they don’t do so reliably.

In this model, we can conceive of adolescence as the period of time after the nucleus accumbens, or the gas pedal of behavior, is fully developed. But while the prefrontal cortex, or the behavioral brakes, are still maturing. In other words, adolescents’ brains respond differently to rewards compared to both children and adults. On this slide, I’m showing a study that involved scanning subjects’ brains as they were receiving either a small or large reward. Young children, shown here in blue, had significant increases in firing whether they received a small reward, on the left, or a large reward, on the right.

Adults, shown in green, made a response that was proportional to the reward size, as you might predict. Adolescents, shown here in black, actually deactivated their brains below baseline in response to small rewards, and made a tremendously large response to a large reward. Adolescents are developmentally wired to seek large neurologic rewards. And herein lies the problem. All psychoactive substances feel good when people use them, because they directly or indirectly result in increased firing in the pleasure and reward center in the brain. In a sense, these substances are hijacking the normal reward pathway.

And while this is neither natural nor healthy, it does fulfill a developmental drive for adolescents. Indeed, the graph from SAMHSA demonstrates that the peak ages for substance use initiation are between 14 and 20. Note that by age 26, substance use initiation is very rare. People who don’t start using a substance in their teens or early adulthood are unlikely ever to start using it, which brings me back to an earlier point. The medicine cabinet reservoir of opioids is a real problem for adolescents. In fact, almost 85% of adolescents who used opioids said they got them or took them from a family member or friend. In other words, they got them from the medicine cabinet reservoir.

And this graph of rates of non-medical opioid use by 12th grade students has the exact same shape as the graph that demonstrates the rates of opioid prescribing. There is another problem too, and that is that teens are not only susceptible to substance use, they are also vulnerable to developing substance use disorders. Substance use disorders are the result of changes to the brain’s pleasure and reward center resulting from repeated exposure to exogenous psychoactive substances.

In adults, the mature prefrontal cortices seem to provide some protection, but in teens, the prefrontal cortices are still developing and can’t offer that protection. In fact, the odds of developing a substance use disorder decreased by about 5% for each year that non-medical substance use is delayed. This chart shows the same thing in a different way. Here we can see that children who initiate non-medical opioid use before their 13th birthday have more than a 40% chance of developing an opioid use disorder. For adults who initiate after 21, the risk falls by about half to approximately 20%.

Use of other substances, including nicotine, alcohol, and cannabis also increase the odds of developing an opioid use disorder. By more than two times for teens who use nicotine, and buy more than almost three and a half times for teens who use cannabis. The reasons or intention for use also matter. In a study done in Michigan, about half of the participants said that they used opioids non-medically in order to treat pain, while the other half said they use them to experiment or get high.

Those who used recreationally had nearly 3.5 times the risk of developing opioid addiction compared to non-users. Those who used to treat pain had about 1.8 times the risk. And another study found that teens who were prescribed opioids, and used them as directed, also had an increased risk of developing opioid addiction, though it was smaller than either of the other two groups, with about a 30% increase in odds. Other factors including mental health disorders, family history of substance use disorders, also increased the risk of addiction among people who use substances.

I now want to switch gears and spend a few moments to discuss the role of the pediatrician in combating the opioid epidemic. First of all, I encourage healthcare professionals to screen all of the adolescents that they provide care for, with the goal of screening kids annually. I’m showing the popular S2BI screen, developed here at Boston Children’s Hospital. The first three questions screen for tobacco, nicotine, alcohol, and cannabis use disorders. Any patient who reports past year use to one of these big three is then asked four subsequent questions, including one about past year non-medical prescription use.

This is an excellent way to identify teens who are using opioids non-medically. Our primary care partners have found that approximately 4% of their teen patients report non-medical prescription opioids use. And that opens an excellent opportunity to talk about the risks of opioids. This table shows the major reasons the teens give for using substances. More than a third of teens think that opioids are safer to use and have fewer side effects than street drugs.

I also want to remind us, as prescribers, that we need to work out patient’s goals for pain management. I did a Google image search for the word pain free, and I found thousands of hits like these. While these books and magazines are largely focused on lifestyle issues such as yoga and exercise routines that are healthy for managing pain, note that they all promote pain free living.

This has become a cultural expectation, but it may not be realistic in all situations. Some things in life are painful, and if we try to medicate to a point of being pain free, we’re probably overmedicating. This slide reminds us of the importance of medical treatments and non-opioid medications. And for patients with chronic pain, assessing for, and treating, mental health disorders is a critical component of care.

If you are going to treat with opioids, keep doses low and prescriptions small. Remember, we want to get binding in the spinal cord while sparing other parts of the central nervous system. We still have the opioid reservoir, and we need to get rid of it. Remind parents to get rid of unused prescriptions properly, such as on prescription take back days. I would also like to encourage every prescriber, and especially pediatricians, to obtain a waiver in order to prescribe buprenorphine to your patients with opioid use disorder.

The American Academy of Pediatrics recommends medication treatment for adolescents with opioid use disorder, but unfortunately, only about 1% of all US addiction medicine board diplomats are pediatricians, leaving few physicians who can support adolescents with substance use disorders. In order to be waivered, prescribers must complete eight hours of training. There’s a special buprenorphine waiver course specifically for healthcare professionals who treat adolescents and young adults.

I will end with a couple of summary points. Adolescents are developmentally at high risk for using substances and developing substance use disorders. Healthcare professionals can play a big role in prevention through education and best prescribing practices. Substance use disorders should be treated in the least restrictive setting, which is often in primary care. Thank you very much for your attention.

Sharon Levy, MD, MPH Director, Adolescent Substance Use and Addiction Program Associate Professor in Pediatrics, Harvard Medical School

The most common focus when people discuss substance use is the impact it has on infants and adults, despite evidence of the impact adolescent substance use has on adults, and the increasing number of adolescents who meet diagnostic criteria for a substance use disorder. This presentation will focus on the neurobiological effects of opioid use in adolescents, as well as primary prevention, secondary prevention and treatment options. 

Objectives: 

At the conclusion of this educational program, learners will be able to:

  1. Explain what part of the brain develops during adolescence and how that relates to substance use;
  2. Describe how to screen for an intervene with teens that report non- medical opioid use
  3. Discuss the importance of medication assisted treatment for opioid use disorders

In support of improving patient care, Boston Children’s Hospital is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

Physicians

Boston Children’s Hospital designates this live activity for a maximum of 0.5 AMA PRA Category 1 Credits ™. Physicians should claim only credit commensurate with the extent of their participation in this activity.

Boston Children’s Hospital adheres to all ACCME Essential Areas, Standards, and Policies. It is Boston Children’s policy that those who have influenced the content of a CME activity (e.g. planners, faculty, authors, reviewers and others) disclose all relevant financial relationships with commercial entities so that Boston Children’s may identify and resolve any conflicts of interest prior to the activity. These disclosures will be provided in the activity materials along with disclosure of any commercial support received for the activity. Additionally, faculty members have been instructed to disclose any limitations of data and unlabeled or investigational uses of products during their presentations.

The following planners, speakers, and content reviewers, on behalf of themselves, have reported the following relevant financial relationships with any entity producing, marketing, reselling, or distributing health care goods or services consumed by, or used on patients: 

Sharon Levy, MD, MPH

Consultant- Orexo