Evidence / 2019
Psychosis with Methylphenidate or Amphetamine in Patients with ADHD
Moran LV, Ongur D, Hsu J, Castro VM, Perlis RH, Schneeweiss S (2019). New England Journal of Medicine.
- Population
- Adolescents and young adults (13–25) newly prescribed a stimulant for ADHD, US insurance claims
- Sample
- 337,919 people in two US claims databases; matched new-user comparison
- Condition
- ADHD; incident psychosis defined by diagnosis plus antipsychotic prescription
- Medication focus
- Amphetamine versus methylphenidate
- Jurisdiction
- United States
- Last reviewed
- 1 September 2026
- PMID
- 30893533
- DOI
- 10.1056/NEJMoa1813751
Plain-language finding
In a new-user observational comparison, amphetamine use was associated with a greater risk of a subsequent psychosis episode than methylphenidate. Psychosis events were uncommon in both groups (reported as 0.21% versus 0.10% in the paper’s primary comparison).
Important limitation
Observational claims data cannot prove causation. Residual confounding, diagnostic coding, and US prescribing patterns limit generalisation. The outcome definition required both a psychosis diagnosis and an antipsychotic prescription. Uncommon events in large samples still matter clinically for the people who experience them.
Why we cite this
The most widely cited comparative observational study of stimulant class and incident psychosis in ADHD treatment.
adhd · amphetamine · methylphenidate · psychosis · observational
Research demonstrates a statistical relationship. Association is not causation. Timing, dose, confounding and missing data still matter.
Claims this source supports
Prescription amphetamine treatment has been associated with an uncommon increased occurrence of psychotic symptoms compared with methylphenidate in a large observational study of young people. The events were uncommon in both groups. Association is not proof that amphetamine caused psychosis in any individual.
Last reviewed 1 September 2026