Risk of non-fatal overdose and polysubstance use in a longitudinal study with people who inject drugs in Tijuana, Mexico

Introduction: Among people who inject drugs (PWID), polysubstance use has been associated with fatal and non-fatal overdose (NFOD). However, the risk of overdose due to the cumulative number of various recently used drug types remains unexplored. We estimated the risk of NFOD for different polysubstance use categories among PWID in Tijuana, Mexico.

Methods: Data came from 661 participants followed for 2 years in Proyecto El Cuete-IV, an ongoing prospective cohort of PWID. A multivariable Cox model was used to assess the cumulative impact of polysubstance use on the time to NFOD. We used the Cochran-Armitage test to evaluate a dose-response relationship between number of polysubstance use categories and NFOD.

Results: We observed 115 NFOD among 1029.2 person-years of follow-up (incidence rate: 11.2 per 100 person-years; 95% confidence interval [CI] 9.3-13.3). Relative to those who used one drug class, the adjusted hazard ratio of NFOD for individuals reporting using two drug classes was 1.11 (95% CI 0.69-1.79), three drug classes was 2.00 (95% CI 1.16-3.44) and for those reporting three compared to two was 1.79 (95% CI 1.09-2.97). A significant Cochran-Armitage trend test (P < 0.001) suggested a dose-response relationship.

Discussion and conclusions: Polysubstance use was associated with increased risk of NFOD with a dose-response relationship over 2 years. We identified a subgroup of PWID at high risk of NFOD who reported concurrent use of opioids, stimulants and benzodiazepines. Prioritising tailored harm reduction and overdose prevention interventions for PWID who use multiple substances in Tijuana is needed.