Illicit drug supply, naloxone availability, and overdose mortality in the fentanyl era: a systematic review

Background: The overdose crisis is shaped by increasing synthetic opioids and expanding access to naloxone. We synthesized evidence on associations between illicit drug supply, naloxone availability/distribution, and overdose mortality. Methods: Following PRISMA, we searched 4 databases for studies between 2015 and 2025. Eligible studies examined associations of drug supply indicators or naloxone interventions, and overdose mortality. Data were extracted and synthesized narratively. Results: Forty-seven studies met inclusion criteria. Eighteen studies assessed drug supply changes and all but 2 found significant positive associations between increased fentanyl reports in drug seizures and overdose mortality. Drug seizure data were interpreted as indicators of supply trends or as enforcement disruptions. Thirty-one studies assessed naloxone availability. Thirteen studies reported naloxone access laws, take-home naloxone programs, and/or community interventions were associated with reductions in overdose deaths. Nine studies reported null effects, particularly during the COVID-19 pandemic. Conclusions: Fentanyl reports in drug seizures and drug potency are key drivers of overdose mortality. This review highlights variability in interpreting drug seizure data and the need for clearer conceptualization in future research. Naloxone interventions show promise but depend on consistent implementation and effective targeting of high-risk populations. Coordinated public health strategies are needed to monitor the drug market and strengthen overdose prevention.