Short-Acting Opioids Needed for Withdrawal in US Hospitals, Say Experts

Marcia Frellick

November 23, 2021

Short-acting opioids may complement methadone and buprenorphine for opioid withdrawal symptoms in U.S. hospitals, say authors of an opinion piece calling for rethinking current strategies for opioid withdrawal in this country.

The commentary by Robert A. Kleinman, MD, with the Centre for Addiction and Mental Health, and department of psychiatry, University of Toronto, and Sarah E. Wakeman, MD, with the division of general internal medicine at Massachusetts General Hospital, and Harvard Medical School, Boston, was published in Annals of Internal Medicine.

Currently, short-acting opioids are not recommended in the United States for opioid withdrawal symptoms (OWS) management in the hospital, the authors wrote. Instead, withdrawal symptoms are typically treated, followed by methadone or buprenorphine or nonopioid medications, but many patients don't get enough relief. Undertreated withdrawal can result in patients leaving the hospital against medical advice, which is linked with higher risk of death.

Addiction specialist Elisabeth Poorman, MD, of the University of Illinois Chicago, said in an interview that she agrees it's time to start shifting the thinking on using short-acting opioids for OWS in hospitals. Use varies greatly by hospital and by clinician, she said.

"It's time to let evidence guide us and to be flexible," Poorman said.

The commentary authors noted that with methadone, patients must wait several hours for maximal symptom reduction, and the full benefits of methadone treatment are not realized until days after initiation.

Rapid initiation of methadone may be feasible in hospitals and has been proposed as an option, but further study is necessary before widespread use, the authors wrote.

Short-Acting Opioids May Address Limitations of Other Opioids

Lofexidine, an alpha-2-adrenergic agonist, is the only drug approved by the Food and Drug Administration specifically for OWS.

"However," the authors said, "more than half of patients with OWS treated with lofexidine in phase 3 efficacy trials dropped out by day five. Clonidine, another alpha-2-agonist used off label to treat OWS, has similar effects to those of lofexidine. "

Therefore, short-acting opioids may complement methadone and buprenorphine in treating OWS in the hospital by addressing their limitations, the authors wrote.

Kleinman and Wakeman also say short-acting opioids may help with starting buprenorphine for patients exposed to fentanyl, because short-acting opioids can relieve withdrawal symptoms while fentanyl is metabolized and excreted.

Supplementation with short-acting opioids within the hospital can relieve withdrawal symptoms and help keep patients comfortable while methadone is titrated to more effective doses for long-term treatment, they wrote.

With short-acting opioids, patients may become more engaged in their care with, for example, a tamper-proof, patient-controlled analgesia pump, which would allow them to have more autonomy in administration of opioids to relieve pain and withdrawal symptoms, the authors wrote.

Kleinman and Wakeman noted that many patients who inject drugs already consume short-acting illicit drugs in the hospital, typically in washrooms and smoking areas, so supervised use of short-acting opioids helps eliminate the risk for unwitnessed overdoses.

Barriers to Short-Acting Opioid Use

Despite use of short-acting opioids internationally, barriers in the United States include limited prospective, randomized, controlled research on their benefits. There is limited institutional support for such approaches, and concerns and stigma around providing opioids to patients with OUD.

"[M]any institutions have insufficient numbers of providers who are both confident and competent with standard buprenorphine and methadone initiation approaches, a prerequisite before adopting more complex regimens," the authors wrote.

Short-acting, full-agonist opioids, as a complement to methadone or buprenorphine, is already recommended for inpatients with OUD who are experiencing acute pain.

But the authors argue it should be an option when pain is not present, but methadone or buprenorphine have not provided enough OWS relief.

When Short-Acting Opioids Are Helpful, According to Outside Expert

Poorman agrees and says she has found short-acting opioids simple to use in the hospital and very helpful in two situations.

One is when patients are very clear that they don't want any medication for opioid use disorder, but they do want to be treated for their acute medical issue.

"I thought that was a fantastic tool to have to demonstrate we're listening to them and weren't trying to impose something on them and left the door open to come back when they did want treatment, which many of them did," Poorman said.

The second situation is when the patient is uncertain about options but very afraid of precipitated withdrawal from buprenorphine.

She said she then found it easy to switch from those medications to buprenorphine and methadone.

Poorman described a situation she encountered previously where the patient was injecting heroin several times a day for 30-40 years. He was very clear he wasn't going to stop injecting heroin, but he needed medical attention. He was willing to get medical attention, but he told his doctor he didn't want to be uncomfortable while in the hospital.

It was very hard for his doctor to accept relieving his symptoms of withdrawal as part of her job, because she felt as though she was condoning his drug use, Poorman explained.

But Poorman said it's not realistic to think that someone who clearly does not want to stop using is going to stop using because a doctor made that person go through painful withdrawal "that they've structured their whole life around avoiding."

Take-Home Message

"We need to understand that addiction is very complex. A lot of times people come to us distressed, and it's a great time to engage them in care but engaging them in care doesn't mean imposing discomfort or pain on them," Poorman noted. Instead, it means "listening to them, helping them be comfortable in a really stressful situation and then letting them know we are always there for them wherever they are on their disease process or recovery journey so that they can come back to us."

Wakeman previously served on clinical advisory board for Celero Systems and receives textbook royalties from Springer and author payment from UpToDate. Kleinman and Poorman declared no relevant financial relationships.

This article originally appeared on, part of the Medscape Professional Network.


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