{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T16:57:23Z","timestamp":1793120243914,"version":"4.5.0"},"reference-count":61,"publisher":"American Medical Association (AMA)","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Psychiatry"],"published-print":{"date-parts":[[2025,11,1]]},"abstract":"\n Importance<\/jats:title>\n Individuals with attention-deficit\/hyperactivity disorder (ADHD) may present with psychosis or bipolar disorder (BD) following treatment with stimulants. The extent to which this occurs is currently unclear.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To meta-analytically quantify the occurrence of psychosis or BD after exposure to stimulants in individuals with ADHD and assess possible moderating factors.<\/jats:p>\n <\/jats:sec>\n \n Data Sources<\/jats:title>\n PubMed, Web of Science, Ovid\/PsycINFO, and Cochrane Central Register of Reviews were searched from inception until October 1, 2024, without language restrictions.<\/jats:p>\n <\/jats:sec>\n \n Study Selection<\/jats:title>\n \n Studies of any design with\n DSM<\/jats:italic>\n or\n International Classification of Diseases<\/jats:italic>\n \u2013defined ADHD populations exposed to stimulants, where psychosis or BD outcomes were evaluated.\n <\/jats:p>\n <\/jats:sec>\n \n Data Extraction and Synthesis<\/jats:title>\n PRISMA Preferred Reporting Items for Systematic Reviews and Meta-analyses and MOOSE Meta-analysis of Observational Studies in Epidemiology guidelines were followed, the protocol was registered, and the Newcastle-Ottawa scale and Cochrane risk of bias-2 tool were used for quality appraisal. Random-effects meta-analysis, subgroup analyses, and meta-regressions were conducted.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n For the proportion of individuals developing psychotic symptoms, psychotic disorders, and BD, effect sizes are reported as percentages with 95% CIs. For the comparison between amphetamines and methylphenidate, effect sizes are presented as odds ratios with 95% CIs.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Sixteen studies (N\u2009=\u2009391\u202f043; mean [range] age, 12.6 [8.5-31.1] years; 288\u202f199 [73.7%] male) were eligible. Among individuals with ADHD prescribed stimulants, 2.76% (95% CI, 0.73-9.88; k\u2009=\u200910; n\u2009=\u2009237\u202f035), 2.29% (95% CI, 1.52-3.40; k\u2009=\u20094; n\u2009=\u200991\u202f437), and 3.72% (95% CI, 0.77-16.05; k\u2009=\u20094; n\u2009=\u200992\u202f945) developed psychotic symptoms, a psychotic disorder, and BD, respectively. Heterogeneity across the studies was significant (\n I<\/jats:italic>\n 2<\/jats:sup>\n \u2009&amp;gt;\u200995%). Psychosis occurrence risk was significantly higher in individuals exposed to amphetamines than to methylphenidate (odds ratio [OR], 1.57, 95% CI, 1.15-2.16; k\u2009=\u20093, n\u2009=\u2009231\u202f325). Subgroup analyses showed significantly higher prevalence of psychotic symptoms in studies from North America and in those with longer follow-up periods. Increased psychosis occurrence was associated with a higher proportion of female participants, smaller sample sizes, and higher dose of stimulants.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n This systematic review and meta-analysis found a nonnegligible occurrence of psychotic symptoms, psychotic disorders, or BD in individuals with ADHD treated with stimulants. Amphetamines were associated with higher occurrence compared to methylphenidate. The included studies cannot establish causality, highlighting the need for further research, including randomized clinical trials and mirror-image studies comparing individuals exposed and not exposed to stimulants. Nonetheless, clinicians should inform patients about the increased occurrence of psychosis or BD when discussing stimulant pharmacotherapy and systematically monitor for these conditions throughout treatment.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamapsychiatry.2025.2311","type":"journal-article","created":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T15:00:48Z","timestamp":1756911648000},"page":"1103","source":"Crossref","is-referenced-by-count":12,"title":["Occurrence of Psychosis and Bipolar Disorder in Individuals With Attention-Deficit\/Hyperactivity Disorder Treated With Stimulants"],"prefix":"10.1001","volume":"82","author":[{"given":"Gonzalo","family":"Salazar de Pablo","sequence":"first","affiliation":[{"name":"Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King\u2019s College London, London, United Kingdom"},{"name":"Child and Adolescent Mental Health Services, South London and Maudsley National Health Service 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