JAMA Psychiatry

Stimulant treatment for ADHD linked to nonnegligible risk of psychosis, bipolar disorder

September 9, 2025

Study details: This systematic review and meta-analysis included 16 studies (N = 391,043; mean age, 12.6 years; 73.7% male) of individuals with ADHD treated with stimulants. Both observational and interventional designs were analyzed, focusing on the incidence of psychotic symptoms, psychotic disorders, and bipolar disorder (BD) after stimulant initiation. Quality of evidence was assessed using GRADE and USPSTF criteria.

Results: Among stimulant-treated individuals, 2.76% developed psychotic symptoms, 2.29% a psychotic disorder, and 3.72% BD. Amphetamines were associated with a significantly higher risk of psychosis than methylphenidate (odds ratio, 1.57; 95% confidence interval, 1.15–2.16). Risk was elevated in studies with longer follow-up, higher stimulant doses, and greater female representation. Heterogeneity across studies was high.

Clinical impact: While causality remains unconfirmed, the findings highlight the importance of comprehensive psychoeducation, careful monitoring for emergent psychiatric symptoms, and shared decision-making regarding stimulant therapy in ADHD. Clinicians should discuss management strategies with patients and caregivers, particularly when considering amphetamines.

Source:

Salazar de Pablo G, et al. (2025, September 3). JAMA Psychiatry. Occurrence of Psychosis and Bipolar Disorder in Individuals With Attention-Deficit/Hyperactivity Disorder Treated With Stimulants: A Systematic Review and Meta-Analysis. https://pubmed.ncbi.nlm.nih.gov/40900605/