Transition to Schizophrenia Spectrum Disorder Following Emergency Department Visits Due to Substance Use With and Without Psychosis

IMPORTANCE: Episodes of substance-induced psychosis are associated with increased risk of developing a schizophrenia spectrum disorder. However, there are limited data on the transition risk for substance use without psychosis. OBJECTIVES: To quantify the risk of transition to schizophrenia spectrum disorder following an incident emergency department (ED) visit for (1) substance-induced psychosis and (2) substance use without psychosis and to explore factors associated with transition. DESIGN, SETTINGS, AND PARTICIPANTS: A population-based retrospective cohort study (January 2008 to March 2022) of all individuals, aged 14 to 65 years, in Ontario, Canada, with no history of a psychotic disorder. Individuals with incident ED visits for substance use with and without psychosis were compared with members of the general population. MAIN OUTCOMES AND MEASURES: Transition to schizophrenia spectrum disorder using a chart-validated algorithm. Associations between ED visits for substance use and subsequent transition were estimated using cause-specific hazard models. RESULTS: The study included 9 844 497 individuals, aged 14 to 65 years (mean [SD] age, 40.2 [14.7] years; 50.2% female) without a history of psychosis. There were 407 737 individuals with an incident ED visit for substance use, of which 13 784 (3.4%) ED visits were for substance-induced psychosis. Individuals with substance-induced psychosis were at a 163-fold (age- and sex-adjusted hazard ratio [aHR], 163.2; 95% CI, 156.1-170.5) increased risk of transitioning, relative to the general population (3-year risk, 18.5% vs 0.1%). Individuals with an ED visit for substance use without psychosis had a lower relative risk of transitioning (aHR, 9.8; 95% CI, 9.5-10.2; 3-year risk, 1.4%), but incurred more than 3 times the absolute number of transitions (9969 vs 3029). Cannabis use had the highest transition risk among visits with psychosis (aHR, 241.6; 95% CI, 225.5-258.9) and the third-highest risk among visits without psychosis (aHR, 14.3; 95% CI, 13.5-15.2). Younger age and male sex were associated with a higher risk of transition, and the risk of male sex was greater in younger compared with older individuals, particularly for cannabis use. CONCLUSIONS AND RELEVANCE: The findings of this cohort study suggest that ED visits for substance use were associated with an increased risk of developing a schizophrenia spectrum disorder. Although substance-induced psychoses had a greater relative transition risk, subs