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Transition to schizophrenia spectrum disorder following emergency department visits due to substance use with or 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, substance use without psychosis was far more prevalent and resulted in a greater absolute number of transitions. Several factors were associated with higher transition risk, with implications for counseling and early intervention.



Myran DT, Harrison LD, Pugliese M, Solmi M, Anderson KK, Fiedorowicz JG, Perlman CM, Webber C, Finkelstein Y, Tanuseputro P. JAMA Psych. 2023; Sep 27 [Epub ahead of print].

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