In increasing numbers, people with opioid use disorder are being admitted to the hospital with overdoses, infections, or respiratory depression.
“The data basically show that we're seeing it more and more in our emergency rooms and on the inpatient floors,” said hospitalist Pooja Lagisetty, MD, MSc, a research investigator at the Ann Arbor Veterans Affairs Center for Clinical Management and Research. “As physicians treating this patient population, I think we're often left wondering what we're supposed to do in this situation, outside of just stabilizing the patient and treating their acute needs.”
As part of an effort to expand access to addiction treatment, which itself involves controlled substances, the Drug Addiction Treatment Act of 2000 (DATA-2000) allowed physicians to provide office-based treatment. The first of these medications that could be prescribed as part of office-based treatment were approved in 2002: buprenorphine (Subutex and other trade names) and the abuse-deterrent formulation of buprenorphine/naloxone (Suboxone and other trade names).
A stipulation in the law also allows physicians to order the medication (or methadone, the other evidence-based treatment for opioid use disorder) for up to 72 hours for patients hospitalized for an unrelated illness.
Despite this, opioid use disorder and withdrawal still often go untreated in the hospital, leading some patients to leave against medical advice, experts said. They urged hospitalists to obtain their prescriber training in order to better care for these patients and to link them to effective treatment after discharge.
Training to treat
The evidence is clear: Taking buprenorphine or methadone for opioid use disorder increases retention in treatment programs and decreases overdose, drug use, infectious disease transmission, and criminal activity, according to the National Institute on Drug Abuse.
The scientific evidence has only grown in confluence with an epidemic of opioid overdoses that, according to CDC estimates, kills 142 Americans every day.
People with opioid use disorder who receive opioid agonist treatment with methadone have less than one-third the mortality risk of those who do not receive it, according to a systematic review and meta-analysis published in 2017 by The BMJ. Opioid agonist treatment with buprenorphine also appears to be associated with a reduction in mortality, although this finding was based on fewer studies, the reviewers said. Patients who discontinued treatment with either drug had increased mortality risk.
In the U.S., about 250,000 to 300,000 individuals are receiving methadone and an estimated 400,000 to 600,000 individuals are receiving buprenorphine for the treatment of opioid use disorder, according to addiction medicine specialist and researcher David A. Fiellin, MD, professor of medicine, emergency medicine, and public health at Yale School of Medicine in New Haven, Conn.
“At one level, DATA-2000 and the advent of buprenorphine and office-based and primary care-based treatment has effectively doubled the capacity of the U.S. health care system to provide the most effective treatment,” he said.
Yet overall physician uptake has not kept up with the need. “The downside is, the estimates are that there are probably only 15% to 20% of those individuals in the U.S. with opioid use disorder who are currently receiving the most effective treatment strategy,” said Dr. Fiellin.
Physicians who complete the training program can then apply for a waiver from the U.S. Drug Enforcement Agency (DEA) to prescribe buprenorphine to patients with opioid use disorder. Waivered physicians may treat up to 30 patients in the first year and may apply to increase their patient cap to 100 in the second year.
Since 2016, the law also allows experienced prescribers who meet certain requirements to increase their limit even further, to 275 patients. More recent legislation, effective in 2016, also allows nurse practitioners and physician assistants in some states to obtain their DEA waivers after completing 24 hours of buprenorphine training.
Patient limits are not an issue in the inpatient setting, even though studies have suggested that initiating treatment in the hospital can not only stabilize patients but increase their chances of being linked to an outpatient treatment program, said Dr. Lagisetty. “The problem is that not many hospitalists have the ability to do this,” she said. “There's a lot of regulatory barriers and lack of access issues to continued outpatient therapy that make this nearly impossible in most settings.”
In addition to the federal barriers of acquiring training and a DEA waiver, local challenges include a scarcity of outpatient prescribers to take handoffs, said Dr. Lagisetty. “There are very few outpatient doctors to continue the medication or ways to contact those doctors in a streamlined way to make sure that they have availability within the next week or so in order to see a patient,” she said.
As of August 2016, slightly more than 37,000 physicians in the U.S., or fewer than 4% of prescribers, had been waivered to prescribe buprenorphine, according to an ACP position paper titled “Health and Public Policy to Facilitate Effective Prevention and Treatment of Substance Use Disorders Involving Illicit and Prescription Drugs,” which was published in March 2017 by Annals of Internal Medicine. As of one year later, about 39,211 prescribers have been certified, according to the Substance Abuse and Mental Health Services Administration (SAMHSA).
However, listing certification on the SAMHSA website is voluntary and the numbers might therefore be underestimates, explained Chinazo Cunningham, MD, MS, professor of medicine at Albert Einstein College of Medicine and associate chief of the division of general internal medicine at Montefiore Medical Center in New York City.
Despite the challenges, physicians across the country are tackling the opioid epidemic by initiating buprenorphine or methadone in the hospital.
When starting a patient's treatment, the most important step is discerning what he or she wants, said addiction medicine specialist Sarah E. Wakeman, MD, medical director of the Massachusetts General Substance Use Disorder initiative and assistant professor of medicine at Harvard Medical School in Boston. This “readiness work” involves identifying what it is in a patient's life that he or she wants to make better and how to get to that goal, she said.
“Most people want to be healthy and want to not experience overdose and not experience the negative consequences that can go along with severe opioid use disorder,” she said. Buprenorphine or methadone is often “the first important ingredient to get people comfortable” because the medications curb both withdrawal and opioid cravings, said Dr. Wakeman.
Although patients generally prefer buprenorphine as first-line treatment, some may opt for methadone as their first choice (despite the logistical challenges of going to a clinic every day to receive it), especially those who have used the medication in the past and found it to be effective, she said.
If a patient has been receiving methadone, it's wiser to continue treatment with methadone than start buprenorphine, as the latter can precipitate withdrawal, noted Anika Alvanzo, MD, MS, FACP, director of the Substance Use Disorders Consultation Service and assistant professor of medicine at Johns Hopkins University School of Medicine in Baltimore. “You may need to alter their dose, depending on how many days they missed,” she said.
Methadone may also be a better choice than buprenorphine if the patient with opioid addiction has an acute pain syndrome that will require management with opioid analgesics, Dr. Alvanzo said. Because of opioid cross-tolerance, some patients may require higher doses of opioids at shorter intervals to control their pain, she added.
“Methadone may be a better option for patients not already on opioid agonist therapy, as it may be easier to manage their pain. You have to put them on a low dose of methadone to cover their opioid debt and then treat over and above with short-acting opioids to control their pain,” Dr. Alvanzo said.
Similarly, if a patient is already on buprenorphine, he or she can receive full agonists on top of the medication, explained ACP Member Laura Fanucchi, MD, MPH, an assistant professor at University of Kentucky College of Medicine in Lexington. Another option, she said, is to split up buprenorphine dosing to better take advantage of the medication's analgesic properties. “Buprenorphine does certainly treat pain. Furthermore, opioid withdrawal will exacerbate acute pain as well as directly cause generalized pain, and pain will be much more manageable if opioid withdrawal is controlled,” said Dr. Fanucchi.
In the past, methadone was thought to be a more effective analgesic than buprenorphine and therefore best for patients with chronic pain and opioid addiction, added Dr. Wakeman. “But increasingly, we're recognizing that buprenorphine actually can be quite effective in terms of analgesia, so I think that's less and less of a defining line,” she said.
Regardless, treating acute pain with opioid agonists in the hospital does not make a patient's opioid addiction worse, said Dr. Fanucchi. “A lot of times, I hear hospitalists are afraid to give patients who are opioid dependent a full agonist, but you don't make someone's substance use disorder worse to effectively treat pain,” she said.
The decision between starting buprenorphine or methadone involves a conversation with the patient but may ultimately boil down to hospital protocol, Dr. Fanucchi said. Methadone is a riskier drug (e.g., more drug-drug interactions, QT prolongation, greater respiratory depression), “so some argue that buprenorphine might be safer, but some health care systems are already very familiar with methadone, and that's their preferred way to manage it,” she said, adding that the availability of local treatment programs after discharge may also help determine which medication to start.
For patients who come into the hospital already on methadone, hospitalists should not stop the drug unless there are very significant extenuating circumstances, Dr. Alvanzo said. Even prolonged QT syndrome, a common cause for stopping methadone, may not be reason enough.
“There are a number of other medications that can prolong the same interval, and it's not always the methadone,” Dr. Alvanzo said. “Abruptly stopping somebody's methadone during the hospitalization can be very destabilizing and potentially put the patient at risk for overdose once they leave the hospital.” If a physician is very concerned about prolonged QT, a better bet is reducing the methadone dose by 10% to 15% and observing the patient, she said.
Physicians looking to treat opioid addiction might also think of naltrexone, which was approved by the FDA for the treatment of opioid addiction in 1984 and is commonly prescribed to patients with alcohol use disorder. In 2006, the FDA approved an extended-release injectable version of naltrexone (Vivitrol) in conjunction with counseling to prevent relapse of opioid dependence after opioid detox.
But experts agreed that naltrexone's utility in the hospital is limited due to its opioid-blocking properties, which can be problematic if a patient has acute pain, as well as because patients must be abstinent from opioids before starting the medication. “It's difficult for us to use naltrexone because you would need to be off opiates for seven to 10 days,” Dr. Alvanzo said. “Most of the patients we see have used opioids very recently, often the day of admission.”
Unlike opioid agonist treatment, naltrexone won't control opioid withdrawal symptoms or cravings, she said. “Additionally, data shows that opioid agonist medications have superior long-term treatment outcomes” compared to naltrexone, said Dr. Alvanzo.
The bridge to remission
As a resident training in New York City, Dr. Fanucchi often cared for patients with opioid use disorder already on methadone treatment, and these patients could continue treatment after discharge from the hospital.
But in 2012, after moving to Kentucky to work as a hospitalist, she saw a constant stream of young patients in the hospital with such complications of drug use as endocarditis and osteomyelitis but no access to addiction treatment.
“It seemed like nobody was in treatment for substance use disorder, and everyone was being kept in the hospital for weeks and weeks to complete courses of IV antibiotic therapy, and it was just so different than what I had experienced before,” she said. “I felt very strongly that there had to be a better way.”
Dr. Fanucchi educated herself about substance use disorder and obtained her waiver to prescribe buprenorphine. She's now working to increase access to treatment in the hospital by expanding addiction medicine consultation. “This is a fairly relatively new concept in internal medicine,” she said.
Studies have shown that starting methadone or buprenorphine in the hospital or ED is a much more effective strategy than referring people to treatment that starts after hospitalization, Dr. Wakeman said.
As medical director of the inpatient addiction consultation team at Mass General, she uses hospitalization as an opportunity to address withdrawal and initiate treatment for patients who have opioid use disorder detected when nurses screen for alcohol and drug use upon admission to the floors. “One of the approaches we've taken with our inpatient addiction team is to really aggressively start medications at the time of hospitalization,” Dr. Wakeman said.
To measure opioid withdrawal in the inpatient setting, Dr. Fanucchi recommended using a standardized tool, such as the Clinical Opiate Withdrawal Scale (COWS). “It's brief and easy to do and is a good, objective measure of opiate withdrawal and allows us to safely know when we can begin buprenorphine treatment or when opioid withdrawal should really be addressed,” she said, as patients must wait to start buprenorphine until mild to moderate opiate withdrawal is present.
For patients in withdrawal, starting methadone or buprenorphine is a “twofer” that both keeps them comfortable and begins the process of opioid use disorder treatment, Dr. Wakeman noted.
Some hospitalists aren't aware they can order buprenorphine or methadone for short-term treatment of opioid use disorder, according to Dr. Fanucchi. “I have heard that hospitalists don't know they can do that multiple times,” she said.
Although all hospitalists can give these short-term prescriptions during hospitalization, there are two clear reasons to pursue a DEA waiver to prescribe buprenorphine: to learn about properly using the medication in the hospital and to provide a bridging prescription at discharge (about a week's worth of medication), Dr. Fanucchi said.
“I think there's discomfort with the medication,” she said of buprenorphine. “Pharmacologically, it's a little bit nuanced, but it's a safe drug, and once you're familiar with how to use it, then it's not difficult. The potential toxicities are lower than a lot of the drugs hospitalists prescribe all the time.”
At Johns Hopkins, a consultation model similar to Mass General's model links patients to opioid addiction treatment programs, Dr. Alvanzo said. The consult team consists of herself, a nurse coordinator who is a certified addictions registered nurse, and a licensed clinical alcohol and drug counselor with a master's degree in social work.
As of April, the team has added two peer recovery specialists who are in sustained recovery and help encourage hospitalized patients to pursue treatment after discharge, Dr. Alvanzo said. “They, in many instances, are able to relate to and engage patients in ways in which we are unable, so they have been a big bonus to our service,” she said.
A few hospitals, such as those in big cities or with robust outpatient treatment programs, are able to successfully bridge treatment for patients with opioid use disorder, said Dr. Lagisetty. But the reality for many hospitals is that there are very few outpatient doctors who can continue buprenorphine after hospitalization, especially on short notice, she said.
“At this point, we're literally stabilizing patients and sending them back out,” Dr. Lagisetty said. “What I think most hospitals are probably able to do is a social worker visits them during their inpatient stay and gives them a list of outpatient treatment programs” instead of an appointment.
This is where hospitalists with DEA waivers can help, as they're able to write bridge prescriptions so that discharged patients are covered while they transition to outpatient care settings, said Dr. Alvanzo. “It's useful . . . particularly when they don't have the benefit of having a [consult] service like ours,” she said.
Dr. Wakeman recommended getting to know which treatment options are available in your community. The SAMHSA database of buprenorphine prescribers, although not a complete listing, provides practices' addresses and phone numbers and is searchable by region or zip code.
Whether patients are seeking treatment or not, hospitalization is an opportunity to educate them about keeping themselves safe (e.g., using clean needles and syringes), Dr. Fanucchi said. “And then, as hospitalists, we should always be prescribing naloxone overdose kits on discharge and educating patients and families on how to recognize and treat overdose,” she said.
Combating the opioid epidemic is made more difficult by a lack of physician education and training around addiction, according to Dr. Cunningham.
“When I was in medical school, in four years I received one hour of training around addiction. What's sad is that I don't think that's really changed that much in the last 25 years,” she said. “If the doctors are poorly educated, poorly trained, and don't have the confidence to take this on, then they won't take it on.”
However, such education is becoming more common for physicians in training, said addiction medicine specialist Jeanette M. Tetrault, MD, FACP, associate professor of medicine at Yale School of Medicine.
“It's become more recognized that chronic medical conditions and psychiatric conditions are so negatively affected by ongoing substance use,” she said. “If we don't give the trainees the tools to address the substance use, or at least have comfort in talking to patients about it and getting them linked to care, we're really not doing chronic disease management justice.”
To Dr. Cunningham, who has trained residents in addiction treatment as part of Montefiore's program for 15 years, this is long overdue.
“It's new because it's hitting suburbs, it's hitting more affluent populations, but my clinic is in the South Bronx, and this is not new. . . . People were talking about incarcerating everybody, and now all of a sudden we've shifted from incarcerating to talking about treatment, which is great and that's how it should be. It's just the way in which we got to this point is a bit bittersweet,” she said.
Dr. Wakeman likened the epidemic of opioid addiction to HIV, another disease that was once given insufficient attention.
“It was really physicians and the house of medicine responding to a public health crisis and stepping up to offer treatment and to learn more . . . that changed the arc of that epidemic,” she said, adding that opioid overdose is now the top cause of death for Americans under age 50. “If the role of the physician is to relieve pain and suffering and to prevent people from dying, then this is a pretty important thing for physicians to learn how to do.”
HIV research didn't stop at the approval of two or three medications, Dr. Lagisetty added. “Hopefully, this will also spin on more research to develop newer treatment options for these patients, so they don't just have three drugs on the market to treat them,” she said.