Substance-induced psychosis as a risk factor for unipolar depression or anxiety disorders: A nationwide register-based prospective cohort study

Background: Substance-induced psychosis has previously been linked to increased incidence of schizophrenia and bipolar disorder. We aimed to investigate if substance-induced psychosis is associated with increased risk of depression or anxiety. Methods: We conducted a nationwide prospective register-based cohort study from 1994 to 2017, including all individuals with substance-induced psychosis, and age-and-sex matched controls without substance-induced psychosis. We investigated time to either depression or anxiety, as well as time to depression and time to anxiety, in stratified Cox regression models. Results: We included 5,557 individuals with substance-induced psychosis and 55,562 controls. Substance-induced psychosis was associated with increased risk of either depression or anxiety (HR=7.05, 95% CI 6.71-7.41), depression (HR=5.40, 95% CI 4.77-6.11), or anxiety (HR=7.05, 95% CI 5.99-8.31). Analyses of individual types of substance-induced psychosis revealed similar hazard ratios across substances. Associations between substance-induced psychosis and depression or anxiety were stronger in people without preceding alcohol or substance use disorders. While strongest shortly after incident substance-induced psychosis, the increased incidence of depression and anxiety remained more than double over the full period of follow-up. Limitations: Only psychiatric disorders treated either in psychiatric inpatient or outpatient units, supplemented with information on psychiatric medication, was available. Exact times of onset were similarly unknown, and only dates of first treatment were available. Conclusions: Substance-induced psychosis is a strong predictor of later onset of depression or anxiety. Regardless of whether this association is causal, this highlights the need for increased monitoring and possibly improved treatment of patients with substance-induced psychosis.