Early and higher doses of methadone during hospitalization may help reduce the likelihood that patients with opioid use disorder leave the hospital before completing treatment.

A study led by Johns Hopkins researchers and published March 25 in JAMA Network Open found that among hospitalized adults with opioid use disorder, each additional 10 milligrams of methadone given within the first 24 hours of care was associated with about 29% lower odds of patient-directed discharge, defined as leaving the hospital before recommended treatment is complete.

“This study highlights that prioritizing early and adequate treatment of withdrawal can make a meaningful difference in whether patients stay to complete care,” says senior author Will Garneau, M.D., M.P.H., M.H.S., a hospitalist and addiction medicine physician at Johns Hopkins Medicine.

In the retrospective cohort study, investigators examined 554 hospitalized adults with opioid use disorder treated at The Johns Hopkins Hospital between July 2019 and June 2022. They analyzed cumulative methadone doses received within the first 24, 48 and 72 hours after presentation to the emergency department and assessed whether patients discharged themselves prematurely at multiple points during hospitalization.

Among 325 patients who received methadone within the first 24 hours, 13.8% left the hospital before completing treatment. Across analyses, higher methadone dosing early in hospitalization was consistently associated with lower odds of patient-directed discharge at 48, 72 and 96 hours, as well as overall during admission.

Patient-directed discharge occurs in approximately 10% to 20% of hospitalizations among people with opioid use disorder and is linked to higher risks of complications, readmission and death, researchers report. Clinicians say many patients leave early because their pain or withdrawal symptoms are undertreated, which can lead to repeated emergency department visits and hospitalizations.

“People may not realize how often patients cycle through hospitals without completing treatment,” says co-first author Rebecca Meredith, M.D., a hospitalist and assistant professor of medicine at Johns Hopkins. “Inadequate treatment of withdrawal is often what drives patients to leave early. If we can interrupt that cycle, even for a portion of patients, it can have a meaningful impact.”

Previous studies have shown that medications for opioid use disorder may reduce the risk of patient-directed discharge. However, researchers say this study adds important detail by examining both the timing and cumulative dose of methadone treatment early in hospitalization. Investigators used detailed electronic medical record data to track methadone administration alongside other opioid medications and clinical variables, allowing them to evaluate how treatment intensity relates to outcomes.

The findings are particularly relevant in the fentanyl era, when patients often have higher opioid tolerance and may experience more severe withdrawal symptoms during hospitalization. Methadone can help stabilize patients during this transition and may reduce the urgency some feel to leave care prematurely.

The study also reflects broader challenges in caring for hospitalized patients with opioid use disorder. Despite well-established benefits of medications for opioid use disorder, prior research suggests these medications are still underused in inpatient settings due to barriers such as limited training, hospital policies and stigma. Researchers say improving early withdrawal management may help address these gaps while improving outcomes.

Researchers note several limitations of the study, including that it was conducted at a single academic medical center and was observational in design, meaning it cannot establish causation. Larger multicenter studies and randomized clinical trials will be needed to confirm findings and help guide best practices for inpatient methadone dosing.

Still, investigators say the results offer practical insights for clinicians caring for hospitalized patients with opioid use disorder.

“As we continue responding to the opioid crisis, improving how we manage withdrawal in the hospital is critical,” Garneau says. “Helping patients remain in care long enough to complete treatment is an important step toward improving outcomes.”

Additional study authors include Kenneth Feder, Ph.D., assistant research professor at the Johns Hopkins Bloomberg School of Public Health, and Megan Buresh, M.D., associate professor of medicine and public health at The Johns Hopkins University.

This study was funded principally by the National Institutes of Health National Center for Advancing Translational Sciences (NCATS) KL2TR003099 and the Johns Hopkins Division of Hospital Medicine Scholars Fund.