Liver disease, HIV, pregnancy: the ideal med for opioid use disorder varies with the patient
STUDY: Atoui Z et al, Journal of Addictive Diseases 2026
STUDY TYPE: Narrative review
FUNDING: Independent
Background
Methadone, buprenorphine, and extended-release naltrexone all treat opioid use disorder, but comorbidities change the risk/benefit ratio. Consider liver disease, kidney disease, heart disease, HIV, pregnancy, and coexisting alcohol or benzodiazepine use. Rather than withholding treatment, this review tells us how to modify it.
Summary
Liver disease: Consider buprenorphine-only formulations (eg, monthly Sublocade, weekly/monthly Brixadi, or sublingual daily Subutex which is now generic). These perform better than buprenorphine-naloxone, since impaired clearance raises naloxone levels and can trigger withdrawal.
Renal disease: Buprenorphine needs no dose adjustment, while methadone may need a 50 to 75% dose cut once creatinine clearance drops below 10 mL/min.
Cardiac disease: Buprenorphine and naltrexone spare the QTc interval; buprenorphine showed fewer new arrhythmias than methadone (3.81% vs 5.71%). Methadone’s QTc risks are more pronounced with CYP inhibitors, particularly CYP3A4 and 2B6.
HIV: The antiretrovials efavirenz and nevirapine speed methadone clearance and can provoke withdrawal, while buprenorphine mostly avoids these interactions.
Pregnancy: Methadone and buprenorphine are the standard of care, with buprenorphine linked to less neonatal abstinence syndrome and preterm birth. Even with concurrent alcohol or benzodiazepine use, stopping MOUD (medications for opioid use disorder) isn’t usually the best approach in pregnancy. Untreated opioid use disorder carries a twentyfold higher mortality risk.
Adolescents: There is growing evidence for buprenorphine.
Perioperative patients: MOUD should not be withheld, but pain needs to be controlled.
Benzodiazepine use: This is a controversial area, as benzos add to the risk of death with opioid overdose, but stopping benzos may worsen mortality overall by impeding adherence. That lack of treatment raises the death risk 20-fold. Risk mitigation strategies include:
- Careful assessment of the indication for benzodiazepine
- Limit dose to lowest necessar, consider non-benzodiazepines (I often try Silexan/lavender, for its safety and large effect size)
- Careful monitoring with frequent urine drug screens and psychosocial support
- If the patient has benzodiazepine use disorder, a gradual taper and discontinuation is best, as well as for patients with high risks on benzos (eg, falls, respiratory suppression, frequent overdoses). Taper by 5 to 10% every two to four weeks.
- Dr. Aiken’s tip: I’d require that the same provider be in charge of both the benzodiazepine and the MOUD scripts.
Alcohol use disorder: Alcohol use usually requires separate treatment, but is not a reason to withhold MOUD. Naltrexone Injectable addresses both disorders, but requires 7-10 days of opioid abstinence before starting. Methadone carries a higher risk of overdose death with alcohol, but in one study methadone treatment days were associated with a 66% reduction in alcohol-related acute events (falls, injuries, and poisonings), more than with other MOUD therapies.
Practice Implications
- Patients with complex medical problems are at greater risks with MOUD, but the risks can be mitigated, and withholding treatment is often the riskiest approach of all.
- Here’s our beginner’s guide to MOUD from the Carlat Report (the entire Sept 2024 issue).
—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
