Psychotic symptoms during stimulant treatment for attention-deficit/hyperactivity disorder


  • Teresa Sá Department of Child and Adolescent Psychiatry, Centro Materno-Infantil do Norte, Centro Hospitalar e Universitário do Porto
  • Filipa Martins Silva Department of Child and Adolescent Psychiatry, Centro Materno-Infantil do Norte, Centro Hospitalar e Universitário do Porto
  • Patrícia Magalhães Department of Child and Adolescent Psychiatry, Centro Materno-Infantil do Norte, Centro Hospitalar e Universitário do Porto, Portugal
  • Vânia Martins Department of Child and Adolescent Psychiatry, Centro Materno-Infantil do Norte, Centro Hospitalar e Universitário do Porto, Portugal
  • Paula Barrias Department of Child and Adolescent Psychiatry, Centro Materno-Infantil do Norte, Centro Hospitalar e Universitário do Porto, Portugal



ADHD, amphetamine, methylphenidate, psychostimulants, psychotic symptoms


Introduction: Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. Pharmacological treatment, either alone or in combination with psychosocial interventions, is important in the therapeutic strategy. Psychostimulants remain the most effective medication and are generally well tolerated. However, one of its rare but significant side effects is development of psychotic symptoms.
Objectives: To perform a literature review about the risk of psychotic symptoms during ADHD treatment with stimulants and discuss possible pharmacological treatment implications.
Methods: A literature search was conducted on PubMed database using the terms “ADHD”, “central nervous system stimulants”, and “psychosis”. The search was supplemented with data retrieved from published guidelines.
Results and discussion: ADHD diagnosis has been increasing, as well the use of stimulants for its treatment. However, using these drugs is not without controversy. ADHD pharmacological treatment is rarely associated with psychotic symptoms. Reported symptoms include hallucinations and paranoid delusions, and occasionally also euphoria, grandiosity, and other mania and hypomania features. These symptoms are generally short-lived and self-limited within days after stimulant discontinuation. One study comparing amphetamines and methylphenidate suggested that the former was more likely to cause psychosis compared with the latter. Additionally, study authors agreed that stimulant-induced psychosis seems to be associated to susceptibility factors.
Conclusion: Psychostimulants are highly beneficial for ADHD patients. However, small studies and case reports suggest an association with new-onset psychotic symptoms. Physicians should be aware that psychotic symptoms may arise during stimulant ADHD treatment. Further investigation is required to identify patients who are most at risk of experiencing such adverse events.


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Subcommittee on Attention-Deficit/Hyperactivity Disorder, Wolraich M, et al. ADHD: clinical practice guideline for the diagnosis, evaluation, and the treatment of attention-deficit/hyperactivity disorder in children and adolescents. Pediatrics; 2011; 128:1007-22.

National Institute for Health and Care Excellence. Attention deficit hyperactivity disorder: diagnosis and management. NICE, 2018.

Shyu YC, Yuan SS, Lee SY, Yang CJ, Yang KC, Lee TL, et al. Attention-deficit/hyperactivity disorder, methylphenidate use and the risk of developing schizophrenia spectrum disorders: A nationwide population-based study in Taiwan. Schizophr Res. 2015; 168:161-7.

Storebo OJ, Pedersen N, Ramstad E, Kielsholm ML, Nielsen SS, Krogh HB, et al. Methylphenidate for attention deficit hyperactivity disorder (ADHD) in children and adolescents - assessment of adverse events in non-randomised studies. Cochrane Database Syst Rev. 2018. 5. Art. No.: CD012069.

Canadian ADHD Resource Alliance (CADDRA): Canadian ADHD Practice Guidelines, Fourth Edition, Toronto ON; CADDRA, 2018.

Ramstad E, Storebo OJ, Gerner T, Krogh BH, Holmskov M, Magnusson FL, et al. Hallucinations and other psychotic symptoms in response to methylphenidate in children and adolescents with attention- deficit/hyperactivity disorder: a Cochrane systematic review with meta-analysis and trial sequential analysis. Scandinavian Journal of

Child and Adolescent Psychiatry and Psychology. 2018; 6:52-71.

Coghill DR, Banaschewski T, Nagy P, Otero IH, Soutullo C, Yan B, et al. Long-Term Safety and Efficacy of Lisdexamfetamine Dimesylate in Children and Adolescents with ADHD: A Phase IV, 2-Year, Open-Label Study in Europe. CNS Drugs. 2017; 31:625-38.

Greydanus DE, Nazeer A, Patel DR. Psychopharmacology of ADHD in pediatrics: current advances and issues. Neuropsychiatr Dis and Treat. 2009: 5:171-81.

Shibib S and Chalhoub N. Stimulant Induced Psychosis. Child and Adolesc Ment Health. 2009; 14:20-3.

Cortese S, Holtmann M, Banaschewski T, Buitelaar JK, Coghill D, Danckaerts M, et al. Practitioner review: current best practice in the management of adverse events during treatment with ADHD medications in children and adolescents. J of Child Psychol Psychiatry. 2013; 54:227-46.

Moran LV, Ongur D, Hsu J, Castro VM, Perlis RH, Schneeweiss S. Psychosis with Methylphenidate or Amphetamine in Patients with ADHD. N Engl J Med. 2019; 380:1128-38.

Chammas M, Ahronheim GA and Hechtman L. Reintroduction of stimulant treatment for patients with ADHD, after stimulant-related psychosis. Clin Pract. 2014; 11:289-94.

Bramness JG, Gundersen OH, Guterstam J, Rognli BE, Kostenius M, Loberg E-M, et al. Amphetamine-induced psychosis - a separate diagnostic entity or primary psychosis triggered in the vulnerable? BMC Psychiatry. 2012;


Bramness JG, Rognli EB. Psychosis induced by amphetamines. Curr Opin Psychiatry. 2016; 29:236-41.

Cherland E, Fitzpatrick R. Psychotic Side Effects of Psychostimulants: A 5-Year Review. Can J Psychiatry. 1999; 44:811-3.

Cortese S. Psychosis during Attention Deficit-Hyperactivity Disorder - Treatment with Stimulants. N Engl J Med. 2019; 380:1178-80.

Gross-Tsur V, Joseph A, Shalev RS. Hallucinations during methylphenidate therapy. Neurology. 2004; 63:753-4.

Cressman AM, Macdonald EM, Huang A, Gomes T, Paterson MJ, Kurdyak PA, et al. Prescription Stimulant Use and Hospitalization for Psychosis or Mania: A Population-Based Study. J Clin Psychopharmacol. 2015; 35:667-71.

Moran LV, Masters GA, Pingali S, Cohen BM, Liebson E, Rajarethinam RP, et al. Prescription stimulant use is associated with earlier onset of psychosis. J Psychiatr Res. 2015; 71:41-7.

Mosholder AD, Gelperin K, Hammad TA, Phelan K, Johann-Liang R, et al. Hallucinations and Other Psychotic Symptoms Associated with the Use of Attention-Deficit/Hyperactivity Disorder Drugs in Children. Pediatrics. 2009; 123:611-5.

Goodman DW. Lisdexamfetamine Dimesylate (Vyvanse), A Prodrug Stimulant for Attention-Deficit/Hyperactivity Disorder. P&T. 2010; 35:273-86.

Powell SG, Thomsen PH, Frydenberg M, Rasmussen H. Long-Term Treatment of ADHD With Stimulants: A Large Observational Study of Real-Life Patients. Journal of Attention Disorders. 2011; 15:439-51.

Kooij SJ, Bejerot S, Blackwell A, Caci H, Casas-Brugué M, Carpentier PJ, et al. European consensus statement on diagnosis and treatment of adult ADHD: The European Network Adult ADHD. BMC Psychiatry. 2010; 10:67.

Pliszka SR. Pharmacologic Treatment of Attention-Deficit/Hyperactivity Disorder: Efficacy, Safety and Mechanisms of Action. Neuropsychol Rev. 2007; 17:61-72.

Berman SM, Kuczenski R, McCracken JT. Potential adverse effects of amphetamine treatment on brain and behavior: a review. Molecular Psychiatry. 2009; 14:123-42.

Graham J, Banaschewski T, Buitelaar J, Coghill D, Danckaerts M, Dittmann RW. European guidelines on managing adverse effects of medication for ADHD. Eur Child Adolesc Psychiatry. 2011; 20:17-37.

Ross RG. Psychotic and Manic-like Symptoms During Stimulant Treatment of Attention Deficit Hyperactivity Disorder. Am J Psychiatry. 2006; 163:1149-52.

Surles LK, May HJ, Garry JP. Adderall-Induced Psychosis in an Adolescent. J Am Board Fam Prac. 2002; 15:498-500.

Bennett FC, Brown RT, Craver J, Anderson D. Stimulant medication for the child with attention-deficit/ hyperactivity disorder. Pediatric Clinics of North America. 1999; 46:929-44.

Henning A, Kurtom M, Espiridion ED. A Case Study of Acute Stimulant-induced Psychosis. Cureus, 2019. 11:e4126.

Bramness J, Gundersen O, Guterstam J, Rognli E, Konstenius M, Loberg EM, et al. Amphetamine-induced psychosis - a separate diagnostic entity or primary psychosis triggered in the vulnerable? BMC Psychiatry. 2012; 12:221.

Cortese S, Adamo N, Giovane C, Mohr-Jensen C, Hayes AJ, Carucci S, et al. Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis. Lancet Psychiatry. 2018; 5:727-38.

Martínez-Aguayo J, Arancibia M, Meza-Concha N, Bustamante C, Pérez-Bracchiglione J, Madrid E. Brief psychosis induced by methylphenidate in a child with attention deficit disorder: a case report and literature review. Medwave. 2017; 17:e6980.




How to Cite

Sá T, Silva FM, Magalhães P, Martins V, Barrias P. Psychotic symptoms during stimulant treatment for attention-deficit/hyperactivity disorder. REVNEC [Internet]. 2020Mar.24 [cited 2022Aug.13];29(1):23-8. Available from:



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