Selective Serotonin Reuptake Inhibitor Treatment in Adolescence and Subsequent Risk of Nonaffective Psychosis: A Quasi‐Experimental Study

OBJECTIVE: Psychotic disorders are frequently preceded by common mental disorders (CMDs), like depression and anxiety. It remains unclear whether treating CMDs in adolescence can reduce subsequent psychosis risk. We applied quasi-experimental methods to national register data to assess whether a causal relationship exists between selective serotonin reuptake inhibitor (SSRI) treatment in adolescence and subsequent risk of psychosis. METHODS: Using the secure anonymized information linkage databank, we identified individuals living in Wales (born between 1991 and 1998) with depression who attended Child and Adolescent Mental Health Services. We employed an instrumental variable (IV) analysis, using regional variation in SSRI prescribing practice to estimate the causal effect of cumulative SSRI treatment on psychosis risk, applying two-stage least squares and IV probit models. RESULTS: Our cohort included n = 6615 individuals with adolescent depression. We found no evidence that cumulative SSRI prescription influenced the psychosis risk across intervention windows (1 year: β: 0.114, CI: -0.049, 0.276; 2 years: β 0.062, CI: -0.114, 0.239; 3 years: β 0.021, CI: -0.125, 0.168). CONCLUSION: This quasi-experimental study found no evidence of a causal relationship between SSRI treatment in adolescence and later psychosis risk. Our findings do not support the hypothesis that SSRI treatment of CMDs in adolescence prevents later psychosis.