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 [1].
MAT improves real-world function
Systematic review evidence links MAT for OUD to better employment, legal outcomes, and family functioning, beyond abstinence endpoints [2].
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 [3].
Expanding utilization is critical
Targeted interventions (navigation, outreach, ED-initiated pathways) can increase SUD treatment initiation and retention, addressing the persistent treatment gap [4].
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 [5].
Evidence highlights
Lowest overdose-related acute care risk in cohort data [1]
Buprenorphine vs other MAT
Improved employment, legal, family functioning (systematic review) [2]
Functional outcomes with MAT for OUD
Reduced substance use and improved mental health in pilot program [3]
6-month MOUD outcomes
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.
1
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 [1], while systematic review evidence documents improved functional outcomes with MAT broadly [2].
2
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 [6], [7].
3
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 [8], [7].
4
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 [4].
5
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 [5].
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 [1].
Methadone: Highly effective; prioritize for patients with high tolerance, prior buprenorphine nonresponse, or preference; requires OTP access [7].
XR-Naltrexone: Effective if induction barrier overcome; requires adequate opioid-free period; consider in highly structured settings [7].
All MOUD improve functional outcomes and social stability (employment, legal, family) per systematic review [2].
Initiation and Retention Tactics
ED-initiated MOUD and same-day access pathways increase treatment initiation [4].
Care navigation, proactive outreach, and telehealth follow-up improve attendance and continuity [4].
Program-level results show decreased use and improved mental health within 6 months of MOUD enrollment [3].
Safety Considerations
Co-prescribe naloxone for OUD; counsel on overdose prevention [6].
XR-naltrexone: Ensure no physiologic dependence before first dose to avoid precipitated withdrawal [7].
Methadone: Monitor QTc and drug–drug interactions; supervise dosing per regulations [7].
Buprenorphine: Use micro-induction when fentanyl exposure raises precipitated withdrawal risk (practice evolving; align with local protocols) [7].
Frontier and Adjunctive Therapies
Psychedelic-assisted therapies show early signals but heterogeneity and risk of bias limit certainty; consider only in research settings [5].
Neuroscience-informed targets are under active investigation; translation to routine care remains limited [9].
Behavioral integration (CBT, contingency management, mutual-help) remains essential across SUDs [6], [7].
Systems and Policy Levers
Low-barrier access (same-day starts, bridge clinics) increases uptake [4], [3].
Stigma reduction and workforce training improve initiation and retention [10], [7].
Align formularies and reimbursement to support long-acting formulations and contingency management where permitted [4].
References
Source material
Primary literature that informs this article.
Association of Medication-Assisted Therapy and Risk ...
pmc.ncbi.nlm.nih.gov
Effects of medication assisted treatment (MAT) for opioid ...
www.sciencedirect.com
Outcomes from the medication assisted treatment pilot ...
link.springer.com
Strategies to improve treatment utilization for substance ...
www.sciencedirect.com
Psychedelic‐assisted treatment for substance use disorder
onlinelibrary.wiley.com
Treatment of Substance Use Disorders
www.cdc.gov
Substance use disorders: a comprehensive update ...
pmc.ncbi.nlm.nih.gov
Recent advances in pharmacological management of ...
journals.lww.com
Neuroscience and addiction research: current advances ...
link.springer.com
The Treatment of Substance Use Disorders: Recent ...
karger.com
A Comparison of Medication-Assisted Treatment Options for...
journals.lww.com
Recent advances in pharmacotherapy
journals.lww.com
Recent advances in the treatment of opiate addiction
link.springer.com
Substance Use Disorders and Medication-Assisted ...
pubmed.ncbi.nlm.nih.gov
Medication Assisted Treatment Program Policies: Opinions ...
pmc.ncbi.nlm.nih.gov