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

Author/s: 
Miriam T H Harris, Zoe M Weinstein, Alexander Y Walley

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.

Keywords 
Opiates Opioid Use Disorder opioid abuse opioid overdose methadone

Integrating Buprenorphine for Opioid Use Disorder into Rural, Primary Care Settings

Author/s: 
Jessica J Wyse, Alison Eckhardt, Summer Newell, Adam J Gordon, Benjamin J Morasco

Background: Medications for opioid use disorder (MOUD) including buprenorphine are effective, but underutilized. Rural patients experience pronounced disparities in access. To reach rural patients, the US Department of Veterans Affairs (VA) has sought to expand buprenorphine prescribing beyond specialty settings and into primary care.

Objective: Although challenges remain, some rural VA health care systems have begun offering opioid use disorder (OUD) treatment with buprenorphine in primary care. We conducted interviews with clinicians, leaders, and staff within these systems to understand how this outcome had been achieved.

Design: Using administrative data from the VA Corporate Data Warehouse (CDW), we identified rural VA health care systems that had improved their rate of primary care-based buprenorphine prescribing over the period 2015-2020. We conducted qualitative interviews (n = 30) with staff involved in implementing or prescribing buprenorphine in these systems to understand the processes that had facilitated implementation.

Participants: Clinicians, staff, and leaders embedded within rural VA health care systems located in the Northwest, West, Midwest (2), South, and Northeast.

Approach: Qualitative interviews were analyzed using a mixed inductive/deductive approach.

Key results: Interviews revealed the processes through which buprenorphine was integrated into primary care, as well as processes insufficient to enact change. Implementation was often initially catalyzed through a targeted hire. Champions then engaged clinicians and leaders one-on-one to "pitch" the case, describe concordance between buprenorphine prescribing and existing goals, and delineate the supportive role that they could provide. Sites were prepared for implementation by developing new clinical teams and redesigning clinical processes. Each of these processes was made possible with the active, instrumental support of leadership.

Conclusions: Results suggest that rural systems seeking to improve buprenorphine accessibility in primary care may need to alter primary care structures to accommodate buprenorphine prescribing, whether through new hires, team development, or clinical redesign.

Keywords 
opioid agonist Opioid Use Disorder rural veterans

Chronic Constipation

Author/s: 
Bharucha, AE, Wald, A

Constipation is a common symptom that may be primary (idiopathic or functional) or associated with a number of disorders or medications. Although most constipation is self-managed by patients, 22% seek health care, mostly to primary care physicians (>50%) and gastroenterologists (14%), resulting in large expenditures for diagnostic testing and treatments. There is strong evidence that stimulant and osmotic laxatives, intestinal secretagogues, and peripherally restricted μ-opiate antagonists are effective and safe; the lattermost drugs are a major advance for managing opioid-induced constipation. Constipation that is refractory to available laxatives should be evaluated for defecatory disorders and slow-transit constipation using studies of anorectal function and colonic transit. Defecatory disorders are often responsive to biofeedback therapies, whereas slow-transit constipation may require surgical intervention in selected patients. Both efficacy and cost should guide the choice of treatment for functional constipation and opiate-induced constipation. Currently, no studies have compared inexpensive laxatives with newer drugs that work by other mechanisms.

Keywords 
chronic constipation constipation laxatives opiod-induced consitpation

Buprenorphine to Treat Opioid Use Disorder: A Practical Guide

Author/s: 
Nissly, Tanner, Levy, Robert

Opioids were involved in 42,249 deaths in the United States in 2016, and opioid overdoses have quintupled since 1999.1 Among the causes behind these statistics is increased opiate prescribing by physicians—with primary care providers accounting for about one half of opiate prescriptions.2 As a result, the Centers for Disease Control and Prevention has issued a 4-part response for physicians,3 which includes careful opiate prescribing, expanded access to naloxone, prevention of opioid use disorder (OUD), and expanded use of medication-assisted treatment (MAT) of addiction— with the goal of preventing and managing OUD.

Keywords 
Buprenorphine opioid-use disorder
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