Theodore Cicero’s research changed direction when he encountered a 20-year-old who was taking opioids — but not to get high.
The young man was struggling with depression, low self-esteem and social anxiety. He was taking drugs because he believed they made him a better, more popular person. He was more social, more relaxed and was able to approach women in bars and start conversations. And he was taking opioids despite the disastrous consequences he knew they could have.
Cicero, PhD, the John P. Feighner Professor of Psychiatry, has surveyed 25,000 addicts on why they use drugs. It’s stories like the young man’s that illuminate the challenge medical professionals face in fighting drug use.
“The typical survey response is not that they are getting high, but that it relieves their depression, they feel less anxious,” Cicero said. “Many people feel they are actually better individuals when they’re taking drugs because they are more outgoing. People think they function better. That’s a difficult thing to combat.”
This is the power opioids, such as the prescription pain pill oxycodone or the more easily obtained illegal heroin, have on many individuals and is one major reason the drugs are so addictive. In 2014, drug overdoses surpassed automobile accidents as the No. 1 cause of accidental death for the first time in U.S. history. And although not all of these overdoses are due to opioids, 91 Americans die every day from an opioid overdose, according to the Centers for Disease Control and Prevention (CDC). CDC data also show that 60 percent of overdoses occur in patients with legitimate prescriptions from a single doctor.
For 25 years, Cicero has been ahead of this developing crisis, charting addicts’ motivations and predicting emerging abuse patterns around the country. Cicero and colleagues were the first to identify changing demographics as opioid addiction spread from inner cities to the suburbs, and also predicted the shift from painkillers to heroin to synthetic opioids like fentanyl.
How did we get here?
“There are two events that happened in the late ’90s and early 2000s that have led to where we are right now,” Cicero said.
In 2001, the Joint Commission accrediting organization, advocating on behalf of patients, issued a set of standards outlining how the health-care industry was vastly undertreating pain. The report recommended that health-care workers consider pain as the “fifth vital sign,” along with monitoring of a patient’s temperature, pulse, respiration and blood pressure.
As a result, health-care workers routinely began asking patients to rate their pain on a pain scale. The overarching message: patients shouldn’t have to endure pain.
The report also urged physicians to prescribe opioids more freely, based on a letter published in 1980 in The New England Journal of Medicine (NEJM). Written by two doctors, the five-sentence letter stated: “We conclude that despite widespread use of narcotic drugs in hospitals, the development of addiction is rare in medical patients with no history of addiction.” Though the letter since has been debunked, drug makers and doctors still cite it as a reason to continue the widespread prescribing of opioids.
Another event that took abuse to a critical level was the 1996 introduction of an extended-release version of oxycodone, one of the most popular opioid painkillers.
Sold under the brand name OxyContin, the new pills could be taken just once or twice a day, rather than every 4 to 6 hours. “For people who had trouble keeping track of their medications, this was an ideal solution,” Cicero said. “Elderly people, for example, especially have memory issues with that.”
This new formulation, however, also was an ideal solution for addicts. For a pill to work over 24 hours, it must contain a large amount of the active drug. Instead of 5 mg, each tablet now contained 80 to 100 mg of oxycodone. Addicts soon learned they could release the drug’s full potency all at once by crushing the new tablets.
The revised formulation also contained no acetaminophen or non-steroidal anti-inflammatory drugs, both of which make snorting and injecting the drug very painful. (Acetaminophen, for instance, burns the nasal passages when snorted.)
“Now all of a sudden we had a pure version of oxycodone that didn’t contain any additives,” Cicero said. The maker of this extended formula and the Food and Drug Administration (FDA) later stated that they did not foresee addicts’ workarounds.
With a new emphasis on curing pain and the discovery of a more potent delivery method, other pharmaceutical companies began producing variations of these pain pills. Doctors became more willing to prescribe opioids in larger amounts. Many of these prescriptions would go unused, stored in medicine cabinets and end up getting stolen, sold and diverted to the streets. “Now you have a ready supply of it on the street because physicians were doing their job and treating pain, but had no indication that this was going to lead to trouble,” Cicero said.
Gathering abuse data
In the 1990s, Cicero worked on an FDA advisory committee evaluating the abuse potential of drugs undergoing approvals. Before long, a drug company sought his help in gaining federal approval for a new opioid named tramadol, or Ultram. To determine its abuse potential, Cicero suggested sending surveys to U.S. drug treatment centers for patients to confidentially complete. Center directors would not read these surveys; instead, responses would go to Cicero’s research group at the School of Medicine. This helped legitimize the project and prompted addicts to be more forthcoming with their answers.
A now-debunked letter in The New England Journal of Medicine deems painkillers as rarely addictive.
The Joint Commission suggests pain is vastly undertreated and urges doctors to consider it as the “fifth vital sign.”
Doctors prescribe larger amounts of opioids, which end up on the street. An extended-release version of OxyContin containing 10 times more active ingredient is developed, making it easier to crush and snort.
As doctors realize the abuse potential, they limit prescriptions, decreasing supply and increasing costs of opioids on the streets.
Drug company makes a version of OxyContin that is more difficult to crush and snort. This inadvertently drives addicts to heroin.
The epidemic increases over time. Addicts’ demographics shift from poor, predominantly black communities to more white, middle- to upper-class communities.
Dealers realize cutting heroin with the far more potent, cheaper, lab-made opioids fentanyl and carfentanil gives users a better — but often fatal — high.
“Addicts felt the survey was for a good purpose and that we were trying to solve a problem that they had,” Cicero said. “They’re desperately looking for someone who will either help them with their treatment or maybe prevent this crisis in the first place.”
Over the past two decades, Cicero’s team has sent out confidential questionnaires to approximately 150 drug treatment centers nationally to better understand addiction. Most clients choose to remain anonymous, but some agree to be identified and even participate in lengthier interviews with Cicero.
Survey data is collected in real time. This enables the researchers to put their “ears to the ground,” identify new types of drug abuse and quickly inform regional first responders and agencies about impending threats.
“I don’t think there’s anyone that does a more thorough and accurate survey of drug abuse than Ted Cicero,” said John Burke, past president of the National Association of Drug Diversion Investigators and a retired Ohio police commander who served on the force more than 50 years. He now runs Pharmaceutical Diversion Education Inc., an organization that educates law enforcement and health professionals about the dangers of diversion (the illegal theft and sales of pharmaceutical drugs).
Cicero’s studies helped verify opioid abuse trends in Ohio, a state hit particularly hard by this crisis. The findings “over and over are consistent with what we see on the street,” Burke said, and have been a reliable source for educating the public about the changing face of opioid abuse.
Cicero and his colleagues also publish survey data and analyses in national scientific journals and keep the FDA abreast of their findings. While the agency collects its own data, the gathering process extends over much longer time periods and is often published years later.
A new drug of choice
When doctors realized the NEJM letter was wrong and that there actually was a very large abuse potential for painkillers, they began limiting the quantity of pills they prescribed. Purdue Pharma also switched to an abuse-deterrent formulation of OxyContin that was much more difficult to crush and snort. These changes kept some of the pills off the streets and slowed their abuse but had the unintended consequence of forcing addicts, who were unlikely to stop using drugs altogether, to find a substitute. That substitute, for the most part, was heroin.
In 2014, Washington University was the first to signal this shift from prescription opioids to heroin, a cheap and easily accessible alternative. As more people used heroin, the less stigmatized it became. Suddenly heroin started showing up in affluent suburban neighborhoods and schools. Cicero’s surveys uncovered these shifts in users’ demographics: Half of those who began using heroin before 1980 were white, but over the past decade nearly 90 percent of those who began using were white.
The surveys also helped reveal the use of fentanyl, a synthetic opioid, which began to show up in much of the heroin responsible for overdoses, and carfentanil, a derivative of fentanyl that is used to tranquilize elephants. Fentanyl and its derivatives are 50 to 100 times more potent than heroin, provide a more intense “high” for the user and are relatively inexpensive to make in the lab.
Knowing fentanyl and similar drugs were becoming a problem has helped federal authorities to better monitor availability and block importation of the drugs into the country. First responders also have learned to use caution as some of these drugs can be deadly — even in small amounts — if accidently inhaled at the scene of an overdose.
Moving beyond fear
All of this misuse has had a chilling effect on doctors, who now may be resistant to prescribing opioids, even to those who need them. “Physicians are really at a disadvantage now not knowing who to treat and who not to treat,” Cicero said. “Given all the publicity surrounding this problem, and now the escalation to heroin, most physicians have gotten to the point where they’re afraid to prescribe these medications.”
Doctors must learn to ask questions about patients’ previous history of drug use, alcohol use and smoking, as well as any past anxiety or depression, Cicero said. These are all potential markers of abuse. Cicero also believes physicians need to be more cognizant about the amount of opioids they are prescribing: Is a 30-day supply really necessary in most cases?
“Physicians are really at a disadvantage now not knowing who to treat and who not to treat.” — Theodore Cicero, PhD
To help improve opioid prescribing practices, Cicero suggests that medical schools add opioid and alternative pain management, as well as addiction education, to the curriculum. Medical students graduating today generally are not equipped to deal with the crisis.
“Most physicians don’t really know how to effectively treat pain. We don’t teach them,” Cicero said. “They don’t know how to manage pain and they certainly don’t know the signs that a potential patient is going to be vulnerable or susceptible to abuse.”
Evan Schwarz, MD, assistant professor of emergency medicine, and his team are on the frontlines, treating at least two to three addicts a night in the Barnes-Jewish Hospital Emergency Department (ED). When possible, the team administers Suboxone, a medication that limits cravings, as part of a project funded by the Behavioral Health Network of Greater St. Louis.
General practitioners can undergo training to learn how to administer Suboxone and similar addiction treatment drugs, Schwarz said. This way, they can treat regular patients who show signs of opioid abuse on an outpatient basis, which could help relieve the strain on treatment centers.
Providing patients with realistic pain management expectations can go a long way in preventing addiction, Schwarz said. Zero pain may not be achievable and patients may need to endure some measure of pain in certain circumstances. When appropriate, physicians and patients should seek out alternative forms of pain control via pain management specialists, physical therapists, meditation and so forth. “We try to let patients understand that we’re going to do our best to control their pain and give them realistic expectations for what we can do,” he said. “And even if we’re prescribing opioids, we want to do it in a safe and limited way because these medications do have risks.”
Signs include: lack of responsiveness, shallow breathing, pinpoint pupils, blue/gray lips or fingernails, clammy/pale face. Call 911.
If, based on these signs, you suspect an overdose, administer Narcan nasal spray in one nostril. The spray is absorbed through the blood vessels in the nasal membranes.
The drug then travels to the brain, where it replaces the opioid molecules that are bound to opioid receptors. Narcan works to revive victims in 2-5 minutes. If needed, administer second dose.
Washington University emergency physicians David Tan, MD, and Jeffrey Siegler, MD, also are leading regional medical training for first responders on naloxone administration. Naloxone, or Narcan, works as an opioid antidote, reversing an overdose within seconds. Narcan has saved nearly 27,000 lives, according to the CDC.
The training is part of a federal grant from the Substance Abuse and Mental Health Services Administration, in partnership with the National Council on Alcoholism and Drug Abuse.
The program educates first responders about misconceptions surrounding opioids. “Some people, when they start the training, are sitting there with a scowl on their face, with their arms crossed,” said Tan, also chief of the emergency medical services section. “And they think that these heroin addicts can choose to stop like we choose to stop at a red light and go at a green light. And it’s just not that easy for many of these people.”
To help prevent repeat overdoses, something the responders see all too often, the training also emphasizes the importance of referring addicts to treatment centers, Tan said.
Even with treatment, though, it is not easy to recover from opioid addiction. “The average number of times our patients have been in treatment is 4.8, almost five times,” Cicero said. “And some people are sober for years and then slip back into it because that feeling that they get with this drug — how it makes them feel like a better person — is going to be with them forever.
“The ability to understand this, to get qualitative data has turned out to be extremely important. And we’re now on the leading edge of being able to use these data methods to understand more about what motivates abuse and how to mitigate it.”
Published: September 18, 2017