Recent post marketing surveillance and observational studies have suggested that prescription stimulants are associated with an increased risk of psychotic experiences. For example, one comprehensive observational study found a strong relationship between stimulant prescription and psychotic experiences even after including multipole potentially confounding covariates in the analyses. This study included 141 individuals; 65% of these individuals with ADHD prescribed stimulants reported having had a psychotic experience, compared to 25% of those with ADHD prescribed a non-stimulant. It is important to note that the individuals included in this study had a family history of major psychiatric disorders and should be interpreted accordingly. Due to the seemingly high occurrence of psychotic episodes following stimulant prescriptions, O’Hare and colleagues conducted a study including 8391 individuals to determine the risk of stimulant prescriptions leading to psychotic experiences.
The main goal of this study was to determine if there is causal effect of stimulant prescription prescriptions resulting in psychotic episodes later in life by utilizing a target trial emulation framework. The purpose of using the target trial emulation framework is to rule out possible confounding variables to more accurately determine the causation of any particular outcome (see Hernán et al.). In this case, researchers utilized variables including eligibility criteria (for prescription stimulants), treatment strategies, treatment assignment, start and end of follow-up, outcomes, causal contrast, and statistical analysis plan. Individuals included in the analysis were between the ages of 9-14 with no previous stimulant prescription in the past year and were required to attend a follow-up visit at 1 year, where psychotic experiences were measured using the Prodromal Questionnaire, with the primary observation being psychotic experiences of at least moderate distress. The target trial was emulated using data from the Adolescent Brain Cognitive Development Study (ABCD Study).
Out of the 8391 participants, a total of 18.9% (n=1590) reported experiencing at least 1 or more psychotic experience of at least moderate distress at the initial intake appointment. At the 1-year follow-up 15.1% (n=1268) of participants reported 1 or more psychotic experiences of at least moderate distress. Overall, this analysis on the surface suggests that prescription stimulants lead to psychotic experiences, however, further analysis revealed that psychotic experiences were themselves a predictor of being prescribed stimulants. After this finding, these researchers utilized the doubly robust method to more rigorously assess the causal relationship between stimulant use and psychotic experiences no longer supported the causal effect of stimulant prescription with psychotic experiences. It is also important to note that individuals were assessed on psychopathology measures, and those individuals who scored higher on psychopathology measures were more likely to report psychotic experiences. In conclusion, this study provides strong evidence that prescription stimulants alone are unlikely to lead to psychotic experiences.
References:
Hernán MA, et al. JAMA. 2022;328(24):2446–2447.
O'Hare K et al. Stimulant Medication Use and Risk of Psychotic Experiences. Pediatrics 2025. Epub ahead of print. Abstract