Methylphenidate Treatment and Risk of Psychotic Disorder

TL;DR

A Finnish study found that methylphenidate treatment for ADHD in children may lower the long-term risk of developing a psychotic disorder.

Contribution

The study is the first to use instrumental variable analysis to assess the long-term impact of methylphenidate on psychosis risk in ADHD patients.

Findings

Methylphenidate treatment was not associated with increased psychosis risk in overall ADHD patients.

Children diagnosed with ADHD before age 13 showed a potential protective effect from sustained methylphenidate treatment.

Adolescent diagnosis groups lacked sufficient data for conclusive analysis.

Abstract

This cohort study of a Finnish national multiyear birth cohort uses instrumental variable analysis to investigate whether methylphenidate alters the long-term risk of psychotic disorder in children with attention-deficit/hyperactivity disorder.

Does methylphenidate alter the long-term risk of psychotic disorder in children with attention-deficit/hyperactivity disorder (ADHD)?

This cohort study of a Finnish national multiyear birth cohort, using instrumental variable analysis, did not find an overall difference in the long-term risk of psychotic disorders in children and adolescents diagnosed with ADHD who were treated with methylphenidate. Looking specifically at childhood (age <13 years) ADHD diagnoses, there was a potential protective effect of sustained methylphenidate treatment against subsequent risk of psychotic disorder.

Methylphenidate treatment of ADHD may have a protective effect against psychosis in individuals diagnosed in childhood.

Methylphenidate is the leading pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD) in childhood and adolescence. Individuals with ADHD have a higher risk of psychosis, but the long-term relationship between methylphenidate and risk of developing psychotic disorders is unknown.

To estimate the relationship between methylphenidate treatment and the risk of nonaffective psychosis in children and adolescents diagnosed with ADHD.

This cohort study included instrumental variable analysis of data linkage from multiple national Finnish registries for all individuals born from 1987 to 1997 (n = 697 289). These registries were used to identify childhood and adolescent ADHD diagnoses (age <18 years) from 2003 onwards. Data were analyzed from June 2023 to December 2025.

Cumulative amount of treatment with methylphenidate used in 4 intervention windows: within 1, 2, 3, and 4 years after ADHD diagnosis. Hospital district prescribing propensities (average prescribing within each hospital district, within each intervention window) were used as instruments.

Diagnosis of nonaffective psychotic disorder (by code from International Statistical Classification of Diseases and Related Health Problems, Tenth Revision) by the end of follow-up (December 31, 2016). Instrumental variable analyses were conducted using 2-stage least squares modeling and the Anderson-Rubin test. Risk differences (RDs) were estimated for each intervention window.

Among 3956 individuals diagnosed with ADHD (3181 male [80.4%], 775 female [19.6%]; median [IQR] age, 14.16 [11.78-15.93] years), 2728 (69.0%) received methylphenidate at least once. A total of 222 individuals (5.7%) were diagnosed with nonaffective psychosis by mean (SD) age 22.16 (2.39) years (range, 19.00-29.81 years). There was substantial variation in hospital district prescribing propensity (for example, first-year range, 0.07 to 0.30). Instrumental variable analysis indicated that sustained treatment with methylphenidate (30 mg/d) was not associated with the risk of nonaffective psychosis in the overall ADHD sample (1-year RD, −0.14; 95% CI, −0.85 to 0.42; and 4-year RD, −0.15; 95% CI, −0.49 to 0.11). Secondary analyses indicated a reduced risk of nonaffective psychosis among individuals diagnosed in childhood (age <13 years: 3-year RD, –0.24; 95% CI, –0.45 to –0.03; P = .03; 4-year RD, –0.21; 95% CI, –0.48 to –0.07; P = .02). An insufficiently strong instrument precluded the same secondary analyses in those diagnosed in adolescence.

This study of national Finnish registry data for individuals with ADHD found no overall relationship between sustained treatment with methylphenidate risk of nonaffective psychosis; in secondary analyses, a potentially protective effect of methylphenidate treatment against later psychosis in children diagnosed with ADHD was found. Further research is needed to evaluate potential effects of treatment in individuals diagnosed in adolescence and adulthood.

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