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Background:
The rise of fentanyl in the unregulated drug supply has driven opioid-related overdoses and deaths in the U.S. Despite extensive research on fentanyl and overdose, the independent contribution of fentanyl to overdose over time remains under-described. We explored the relationships between fentanyl use and non-fatal overdose risk among PWID in San Diego over four years.
Methods:
Between 10/2020 and 05/2024, PWID living in San Diego completed biannual surveys assessing self-reported opioid use (fentanyl, non-fentanyl, or no opioid use) and non-fatal overdoses in the past six months. Multivariable Poisson regressions assessed longitudinal associations between fentanyl use and non-fatal overdose risk. We calculated confounder-adjusted longitudinal average population attributable fraction (LAPAF) to quantify fentanyl’s contribution to overdose risk.
Results:
Among 204 participants, the median age was 40.5 years, 73.0% were male, and 68.1% experienced homelessness. Non-fentanyl opioid use decreased from 35.3% at Visit 1 (10/2020-10/2021) to 5.5% at Visit 6 (10/2023-05/2024), while fentanyl use increased from 51.0% to 62.4% over the same period. Non-fatal overdoses decreased from 22.5% to 15.6% overall during the study period, and from 38.5% to 19.1% among PWID who used fentanyl, driving the overall reduction in non-fatal overdose rates. Poisson regression revealed significant associations between fentanyl use and overdose risk at Visits 1 (Adjusted Relative Risk (ARR) = 5.97, 95% CI: 2.37, 15.00) and 5 (ARR = 4.19, 95% CI: 1.17, 15.00). The overall LAPAF of fentanyl use to non-fatal overdose was 35% (LAPAF 0.35, 95%CI: 0.17, 0.52).
Conclusion:
Rising fentanyl use contributed a large share of overdoses among this cohort of PWID, yet rates among those using fentanyl declined. Disentangling the role of contextual factors such as increased opioid tolerance, reduced fentanyl potency, increased access to harm reduction services, and changes in drug use behaviors will support intervention design to curb overdose rates amid increasing drug supplies
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