Updated October 2025

SUD Pharmacotherapy

Substance Use Disorders: Medication-Assisted Treatment Updates

Medication-assisted treatment (MAT) remains a cornerstone for opioid use disorder with robust reductions in mortality and improved functional outcomes. Emerging data explore psychedelic-assisted therapies and system-level strategies to expand treatment utilization. Evidence is strongest for MOUD (buprenorphine, methadone, XR-naltrexone), with supportive but evolving data for other SUD pharmacotherapies and care-delivery innovations.

Clinical question

What are the most recent, clinically relevant updates on medication-assisted treatment (MAT) for substance use disorders (SUDs), including effectiveness, safety, and implementation advances?

Opioid Use DisorderAlcohol Use DisorderStimulant Use DisorderBuprenorphineMethadoneNaltrexoneImplementation SciencePsychedelic-assisted Therapy

Key points

Buprenorphine stands out for overdose risk reduction

Real-world analyses associate buprenorphine with the lowest risk of overdose-related ED visits/hospitalizations among MAT options, supporting first-line use when feasible ^[15].

MAT improves real-world function

Systematic review evidence links MAT for OUD to better employment, legal outcomes, and family functioning, beyond abstinence endpoints ^[1].

Program-level MOUD delivery matters

Integrated MOUD programs show decreased use and improved physical/mental health by 6 months, underscoring the value of access and continuity strategies ^[11].

Expanding utilization is critical

Targeted interventions (navigation, outreach, ED-initiated pathways) can increase SUD treatment initiation and retention, addressing the persistent treatment gap ^[2].

Frontier therapies are promising but preliminary

Psychedelic-assisted treatments show early efficacy signals across SUDs, but evidence quality is mixed and heterogeneous; use remains investigational ^[6].

Evidence highlights

Lowest overdose-related acute care risk in cohort data ^[15]

Buprenorphine vs other MAT

Improved employment, legal, family functioning (systematic review) ^[1]

Functional outcomes with MAT for OUD

Reduced substance use and improved mental health in pilot program ^[11]

6-month MOUD outcomes

Care Pathway

Evidence-based sequencing for MAT in SUDs

Prioritize mortality reduction and retention for OUD; tailor agents to diagnosis, goals, and setting; integrate behavioral supports to strengthen outcomes.

Opioid Use Disorder (first-line MOUD)

Offer buprenorphine or methadone as first-line; consider XR-naltrexone when opioid-free initiation is feasible. Real-world data favor buprenorphine for overdose-related acute care risk reduction ^[15], while systematic review evidence documents improved functional outcomes with MAT broadly ^[1].

Alcohol Use Disorder

Though not in the search set, guideline-concordant options include naltrexone and acamprosate; extended-release naltrexone may improve adherence. Consider comorbidity, liver disease, and adherence profile. General SUD overviews emphasize medication plus psychosocial support ^[7], ^[13].

Stimulant Use Disorders

No FDA-approved medications; contingency management is most effective adjunct. Investigational agents continue to be explored; comprehensive reviews highlight ongoing pharmacotherapy research with mixed efficacy ^[4], ^[13].

Increase initiation and retention

Implement ED-initiated MOUD, care navigation, telehealth inductions, and low-barrier models to close utilization gaps. Systematic review evidence supports multi-component strategies to improve engagement ^[2].

Consider investigational/adjunctive approaches

Psychedelic-assisted treatments (psilocybin, ketamine, MDMA) show preliminary signals across SUDs but remain investigational, with heterogeneous outcomes and methods; deploy only in research or specialized settings ^[6].

Clinical Pearls

Medication selection, safety, and implementation

Match the agent to clinical goals, comorbidities, and setting; leverage systems strategies to sustain treatment.

OUD: Choosing MOUD

Buprenorphine: Strong safety profile; associated with the lowest overdose-related acute care risk vs other MAT options in cohort data ^[15].

Methadone: Highly effective; prioritize for patients with high tolerance, prior buprenorphine nonresponse, or preference; requires OTP access ^[13].

XR-Naltrexone: Effective if induction barrier overcome; requires adequate opioid-free period; consider in highly structured settings ^[13].

All MOUD improve functional outcomes and social stability (employment, legal, family) per systematic review ^[1].

Initiation and Retention Tactics

ED-initiated MOUD and same-day access pathways increase treatment initiation ^[2].

Care navigation, proactive outreach, and telehealth follow-up improve attendance and continuity ^[2].

Program-level results show decreased use and improved mental health within 6 months of MOUD enrollment ^[11].

Safety Considerations

Co-prescribe naloxone for OUD; counsel on overdose prevention ^[7].

XR-naltrexone: Ensure no physiologic dependence before first dose to avoid precipitated withdrawal ^[13].

Methadone: Monitor QTc and drug–drug interactions; supervise dosing per regulations ^[13].

Buprenorphine: Use micro-induction when fentanyl exposure raises precipitated withdrawal risk (practice evolving; align with local protocols) ^[13].

Frontier and Adjunctive Therapies

Psychedelic-assisted therapies show early signals but heterogeneity and risk of bias limit certainty; consider only in research settings ^[6].

Neuroscience-informed targets are under active investigation; translation to routine care remains limited ^[10].

Behavioral integration (CBT, contingency management, mutual-help) remains essential across SUDs ^[7], ^[13].

Systems and Policy Levers

Low-barrier access (same-day starts, bridge clinics) increases uptake ^[2], ^[11].

Stigma reduction and workforce training improve initiation and retention ^[8], ^[13].

Align formularies and reimbursement to support long-acting formulations and contingency management where permitted ^[2].

References

Source material

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