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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

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.

• Chapter One

  Introduction

• Chapter Two

  Methods

• Chapter Three

  Results

• Chapter Four

  Discussion

• Appendix A

  Food and Drug Administration Warnings Table

• Appendix B

  Search Methodology

• Appendix C

  Risk of Bias Instruments

• Appendix D

  Evidence Table

• Appendix E

  Excluded Publications