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Research Questions

  1. What are the effects of MAT (using buprenorphine, buprenorphine plus naloxone, methadone, or naltrexone) for OUD on functional outcomes compared with wait-list, placebo, treatment without medication, any other comparator, or each other (e.g., buprenorphine versus naltrexone)?
  2. Do the effects vary by type of medication?
  3. Do the effects vary by route of administration (e.g., oral versus injection versus implant)?
  4. Do the effects vary by length of treatment, follow-up time, or later cessation of MAT?
  5. Do the effects vary by treatment modality (e.g., methadone clinic versus prescription medication taken at home)?

This systematic review addresses the question: What are the effects of medication-assisted treatment (MAT) that use buprenorphine, buprenorphine combined with naloxone, methadone, or naltrexone for opioid use disorder (OUD) on functional outcomes compared with wait-list, placebo, treatment without medication, any other comparator, or each other (e.g., buprenorphine versus naltrexone)?

Functional outcomes investigated included cognitive (e.g., memory), physical (e.g., fatigue), occupational (e.g., employment status), social/behavioral (e.g., criminal activity), and neurological (e.g., balance) function.

We searched five scientific research databases from inception to 2017 and reference mined existing reviews. Two independent literature reviewers screened 6,292 citations; 1,327 full-text publications were reviewed in detail and 37 studies met inclusion criteria. Critical appraisals assessed studies in detail, and quality of evidence was rated using established criteria. Results were synthesized in meta-analyses and presented in comprehensive evidence tables. Although MAT patients performed significantly better on some functional outcomes than persons with OUD who did not receive MAT, MAT patients performed worse on several cognitive measures than did matched "healthy" controls with no history of substance use disorder (SUD) or OUD. Because of the moderate-to-high risk of bias of most studies, quality of evidence is low or very low for all findings.

The small number of studies reporting on outcomes of interest and the weaknesses in the body of evidence prevent making strong conclusions about MAT effects on functional outcomes. The literature shows that more research is needed that targets functional outcomes specifically, and there is, in particular, a lack of research evaluating potential differences in functional effects among medication types, the route of administration, treatment modality, and length of treatment.

Key Findings

A comprehensive literature search that screened over 6,000 research citations on the topic identified only 27 randomized controlled trials and ten observational studies that reported on functional outcomes

  • No randomized control trial was rated as high quality, but several observational studies were methodologically sound.
  • The only functional measures reported in more than one study were verbal memory, attention, insomnia, fatigue, and criminal activity.
  • MAT users had twice the risk of injurious traffic accidents than nonusers, according to one large observational study.
  • Based on two studies, it appears that MAT users do not perform worse on verbal memory tasks than healthy controls.
  • One study showed that patients taking buprenorphine or methadone scored higher in aggressive responding than healthy controls.

Evidence was mixed when MAT patients were compared with persons with OUD who were not on MAT

  • One cohort comparison found that fewer buprenorphine patients reported fatigue than did persons with OUD who did not receive MAT; other physical and behavioral/social function outcomes had mixed findings or showed no differences.

There was little statistically robust evidence that treatment effects systematically vary by medication

  • A comparison across randomized controlled trials found a significantly lower prevalence of fatigue in buprenorphine patients compared with methadone patients.

Direct comparisons of functional effects by route of administration, length of treatment, and treatment modality were scarce and reported mixed results and pointed to important research gaps that should be addressed in future studies


  • Clinicians and policy makers should use this comprehensive review summarizing the research evidence on functional outcomes when making recommendations for practice and policy.
  • The report outlines concrete suggestions for research funding agencies that describe the studies needed to support strong conclusions about the effects of MAT on functional outcomes, potential differences among medication types, the role of treatment modalities, and the effect of the length of treatment. Some studies that compared MAT patients to persons with OUD who did not receive MAT reported significant beneficial effects. However, this finding does not imply that performance meets the standards required for military deployment.

This research is sponsored by the Defense Centers of Excellence for Psychological Health and Traumatic Brain Injury and conducted within the Forces and Resources Policy Center of the RAND National Defense Research Institute, a federally funded research and development center sponsored by the Office of the Secretary of Defense, the Joint Staff, the Unified Combatant Commands, the Navy, the Marine Corps, the defense agencies, and the defense Intelligence Community.

This report is part of the RAND research report series. RAND reports present research findings and objective analysis that address the challenges facing the public and private sectors. All RAND reports undergo rigorous peer review to ensure high standards for research quality and objectivity.

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