5.2 Pharmacotherapy of ADHD and the Risk of New-Onset Psychosis in a Geographically Defined Cohort of Youth

Abstract

Epidemiological studies suggested increased risk of psychosis in youth with ADHD who are treated with psychostimulants. A recent study by Moran and colleagues found that youth with ADHD had a higher risk of psychosis when treated with amphetamines compared to methylphenidate. The risk of developing psychosis in other groups of ADHD medications is poorly understood. This population-based study aims to compare the risk of new-onset psychosis between 4 different groups of ADHD medications. We used the Rochester Epidemiology Project (REP) to evaluate patients between January 1, 2005 and December 31, 2018 who were 6 to 18 years old, diagnosed with ADHD, and prescribed amphetamine, methylphenidate, atomoxetine, or alpha-2 agonists. All subjects with psychotic or substance use diagnoses prior to receiving their first qualifying ADHD medication were excluded. The primary outcome was a newly diagnosed psychosis, defined as having a relevant ICD-9 and ICD-10 diagnosis. The risk of psychosis conditioned on ADHD medication class was estimated using a time-varying covariate Cox proportional hazard regression model. We identified 5171 youth (3545 male) who met the inclusion criteria, of which 134 (95 males, 70.9%) were classified as having new-onset psychosis. Male sex was a significant predictor of psychosis (hazard ratio [HR] = 1.904; 95% CI, 1.909-2.783; p = 0.0009). Exposure to atomoxetine was the strongest predictor of psychosis (HR = 2.009; 95% CI, 1.382-2.921; p = 0.0003). Exposure to amphetamines was also found to be a significant predictor of psychosis (HR = 1.612; 95% CI, 1.148-2.263; p = 0.0058). Exposure to methylphenidate was not found to be a significant predictor (HR = 1.022; 95% CI, 0.701-1.491; p = 0.9083). Exposure to alpha-2 agonists trended toward significance as a predictor of the absence of a diagnosis of psychosis (HR = 0.668; 95% CI, 0.421-1.059; p = 0.0860). Our results agree with previously published findings that amphetamines are associated with increased risk for new-onset psychosis. Interestingly, we found the risk of new-onset psychosis to be greatest with atomoxetine and lowest with alpha-2 agonists, which are novel additions to the literature from a large cohort. Finally, we found that male sex is a significant predictor of later diagnosis of psychosis in pediatric patients taking ADHD medication.