Systematic review of real-world data associated with opioid scheduling and nonmedical use

In the context of increased use of buprenorphine for pain management, comparison of real-world data (RWD) on prescription opioid nonmedical use (NMU) based on their controlled substance schedule may assist providers in providing effective pain management therapy while mitigating the risk of opioid NMU.

A systematic literature review of articles reporting RWD on prescription opioid NMU involving Schedule II (CII), Schedule III (CIII), and Schedule IV (CIV) opioid medications was conducted using PubMed®.

Human RWD collected in the United States from January 2010 to December 2023.

Articles reporting RWD of prescription opioid NMU. Exclusions included buprenorphine/methadone medications for opioid use disorder, chronic use, or overdose without clearly established NMU (could not rule out legitimate medical use).

There were 2,585 articles screened for inclusion, 102 articles were assessed with a validated data extraction form, and 16 articles were reviewed that compared NMU and/or secondary NMU-related outcomes. Of these, only five articles contained RWD on NMU; all showed more NMU associated with CII than CIII or CIV opioids. Two articles evaluated buprenorphine (CIII) for analgesia and found lower rates of CIII NMU than comparator CII opioids.

Results of this systematic review support the differentiation in scheduling between CII and CIII/CIV opioid medications with RWD. This study also reveals a research gap in comparing CIII opioid medications for analgesia to CII and CIV opioids, an area of current and future interest, considering the growing use of buprenorphine for pain management, along with initiatives to curb opioid NMU.