University of Oklahoma Health Sciences Center

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Author/s:

Miriam T H Harris, Zoe M Weinstein, Alexander Y Walley

Date Added:

February 16, 2026

Journal/Publication:

JAMA

Publication Date:

February 11, 2026

URL:

Medications for Opioid Use Disorder, Opioid Withdrawal, and Opioid Overdose: A Review

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jama.2025.26348

PMID (1):

41671014

Keywords

Opiates

Opioid Use Disorder

opioid abuse

opioid overdose

methadone

MeSH

substance withdrawal syndrome

RPR Commentary

A review of medications indicated for treatment of patients with opioid use disorders. James W. Mold, MD, MPH

Abstract

Importance: Opioid use disorder (OUD) involves compulsive opioid use that causes substantial distress or impairment at work, school, or home. OUD, which is the third most prevalent substance use disorder worldwide, affected an estimated 3.7% of US adults (9 367 000) in 2022 and caused 53 774 deaths in the US in 2024. Medications for opioid use disorder (MOUD) reduce morbidity and mortality. Individuals with OUD also benefit from medications to treat opioid withdrawal and reverse acute opioid overdose.

Observations: Methadone, buprenorphine, and naltrexone are medications approved by the US Food and Drug Administration (FDA) to reduce unregulated opioid use. Methadone and buprenorphine reduce the risks of overdose and all-cause mortality. However, only 25.1% of people in the US with OUD were treated with these medications in 2022. MOUD should be selected based on shared decision-making that considers availability and convenience of treatment options and patient preferences. Buprenorphine and naltrexone are prescribed in office-based settings and can be taken at home. Outpatients with OUD in the US can only obtain methadone in person at federally regulated clinics. After stopping or substantially reducing use of opioids, individuals with OUD develop symptoms of opioid withdrawal, such as anxiety, insomnia, pain, nausea, vomiting, and diarrhea. Medications for opioid withdrawal include opioid agonists (eg, methadone and buprenorphine), α2-receptor agonists (eg, lofexidine and clonidine), and medications to treat pain (ibuprofen) and nausea (ondansetron). Individuals being treated for acute withdrawal should also be prescribed MOUD to decrease the risk of all-cause mortality (adjusted hazard ratio, 0.52; 95% CI, 0.42-0.63 for MOUD vs no MOUD). Individuals who use opioids may develop opioid overdose, which can cause respiratory depression, stupor, and, if severe, coma and death. Opioid overdose can be treated or can be reversed with naloxone, an opioid antagonist that is FDA approved and should be administered at the lowest dose needed to restore a normal respiratory rate (eg, naloxone 0.4 mg intramuscularly or 2-4 mg intranasally). Community-wide distribution of naloxone to people who use opioids and their social networks has been associated with 25% to 46% lower community opioid overdose rates.

Conclusions and relevance: All individuals with OUD should be offered treatment with MOUD to reduce opioid use. Methadone and buprenorphine decrease opioid-associated and all-cause mortality in patients with OUD. Opioid withdrawal symptoms may be treated with opioid agonists, α2-receptor agonists, and medications for pain and nausea. All individuals with OUD should have access to opioid antagonists, such as naloxone, to treat opioid overdose.