Kenneth K C Man1,2,3,4, David Coghill4,5,6, Esther W Chan2, Wallis C Y Lau2, Chris Hollis4,7,8, Elizabeth Liddle4,7,8, Tobias Banaschewski4,9, Suzanne McCarthy4,10, Antje Neubert4,11, Kapil Sayal4,7,8, Patrick Ip1, Martijn J Schuemie12, Miriam C J M Sturkenboom3, Edmund Sonuga-Barke4,13, Jan Buitelaar4,14, Sara Carucci4,15, Alessandro Zuddas4,15, Hanna Kovshoff4,13, Peter Garas4,16, Peter Nagy4,16, Sarah K Inglis4,5,17, Kerstin Konrad4,18, Alexander Häge4,9, Eric Rosenthal4,19, Ian C K Wong1,2,4,20. 1. Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong. 2. Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong. 3. Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, the Netherlands. 4. The Attention Deficit Hyperactivity Disorder Drugs Use Chronic Effects Consortium. 5. Division of Neuroscience, School of Medicine, University of Dundee, Dundee, Scotland. 6. Departments of Paediatrics and Psychiatry, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Australia. 7. Centre for ADHD and Neuro-developmental Disorders Across the Lifespan, Institute of Mental Health, Nottingham, England. 8. Division of Psychiatry and Applied Psychology, School of Medicine, University of Nottingham, England. 9. Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. 10. School of Pharmacy, University College Cork, Cork, Ireland. 11. Department of Paediatrics and Adolescent Medicine, University Hospital Erlangen, Erlangen, Germany. 12. Janssen Research & Development, LLC, Titusville, New Jersey. 13. Department of Psychology, University of Southampton, Southampton, England. 14. Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboudumc, and Karakter Child and Adolescent Psychiatry, Nijmegen, the Netherlands. 15. Department of Biomedical Sciences, Section Of Neuroscience and Clinical Pharmacology, University of Cagliari, and Child and Adolescent Neuropsychiatry Unit, G. Brotzu Hospital Trust, Cagliari, Italy. 16. Vadaskert Child and Adolescent Psychiatric Hospital, Budapest, Hungary. 17. Tayside Clinical Trials Unit, University of Dundee, Dundee, Scotland. 18. Child Neuropsychology Section, Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Clinics Rheinisch-Westfälische Technische Hochschule Aachen, Aachen, Germany. 19. Evelina London Children's Hospital, London, England. 20. Research Department of Practice and Policy, University College London School of Pharmacy, London, England.
Abstract
Importance: Patients with attention-deficit/hyperactivity disorder (ADHD) are at an increased risk of attempting suicide. Stimulants, such as methylphenidate hydrochloride, are the most common treatment for ADHD, but the association between their therapeutic use and suicide is unclear. Objective: To investigate the association between methylphenidate and the risk of suicide attempts. Design, Setting, and Participants: A population-based, electronic medical records database from the Hong Kong Clinical Data Analysis & Reporting System was used to identify 25 629 individuals aged 6 to 25 years who were treated with methylphenidate between January 1, 2001, and December 31, 2015. Those who had attempted suicide were included in the analysis. A self-controlled case series design was used to control for time-invariant characteristics of the patients. Main Outcomes and Measures: Relative incidence of suicide attempt during periods when patients were exposed to methylphenidate compared with nonexposed periods. Results: Among 25 629 patients with methylphenidate prescriptions, 154 had their first recorded suicide attempt within the study period; of these individuals, 111 (72.1%) were male; mean (SD) age at baseline was 7.15 (2.19) years. The overall incidence of suicide attempts during methylphenidate treatment was 9.27 per 10 000 patient-years. An increased risk of suicide attempts was detected during the 90-day period before methylphenidate was initiated, with an incidence rate ratio (IRR) of 6.55 (95% CI, 3.37-12.72). The IRR remained elevated during the first 90 days of treatment (IRR, 3.91; 95% CI, 1.62-9.42) before returning to baseline levels during ongoing treatment (IRR, 1.35; 95% CI, 0.77-2.38). When the risk during the first 90 days of treatment was compared with the 90 days preceding first treatment, the incidence of suicide attempts was not elevated (IRR, 0.78; 95% CI, 0.26-2.35). Conclusions and Relevance: The incidence of suicide attempts was higher in the period immediately before the start of methylphenidate treatment. The risk remained elevated immediately after the start of methylphenidate treatment and returned to baseline levels during continuation of methylphenidate treatment. The observed higher risk of suicide attempts before treatment may reflect emerging psychiatric symptoms that trigger medical consultations that result in a decision to begin ADHD treatment. Therefore, this study's results do not support a causal association between methylphenidate treatment and suicide attempts.
Importance: Patients with attention-deficit/hyperactivity disorder (ADHD) are at an increased risk of attempting suicide. Stimulants, such as methylphenidate hydrochloride, are the most common treatment for ADHD, but the association between their therapeutic use and suicide is unclear. Objective: To investigate the association between methylphenidate and the risk of suicide attempts. Design, Setting, and Participants: A population-based, electronic medical records database from the Hong Kong Clinical Data Analysis & Reporting System was used to identify 25 629 individuals aged 6 to 25 years who were treated with methylphenidate between January 1, 2001, and December 31, 2015. Those who had attempted suicide were included in the analysis. A self-controlled case series design was used to control for time-invariant characteristics of the patients. Main Outcomes and Measures: Relative incidence of suicide attempt during periods when patients were exposed to methylphenidate compared with nonexposed periods. Results: Among 25 629 patients with methylphenidate prescriptions, 154 had their first recorded suicide attempt within the study period; of these individuals, 111 (72.1%) were male; mean (SD) age at baseline was 7.15 (2.19) years. The overall incidence of suicide attempts during methylphenidate treatment was 9.27 per 10 000 patient-years. An increased risk of suicide attempts was detected during the 90-day period before methylphenidate was initiated, with an incidence rate ratio (IRR) of 6.55 (95% CI, 3.37-12.72). The IRR remained elevated during the first 90 days of treatment (IRR, 3.91; 95% CI, 1.62-9.42) before returning to baseline levels during ongoing treatment (IRR, 1.35; 95% CI, 0.77-2.38). When the risk during the first 90 days of treatment was compared with the 90 days preceding first treatment, the incidence of suicide attempts was not elevated (IRR, 0.78; 95% CI, 0.26-2.35). Conclusions and Relevance: The incidence of suicide attempts was higher in the period immediately before the start of methylphenidate treatment. The risk remained elevated immediately after the start of methylphenidate treatment and returned to baseline levels during continuation of methylphenidate treatment. The observed higher risk of suicide attempts before treatment may reflect emerging psychiatric symptoms that trigger medical consultations that result in a decision to begin ADHD treatment. Therefore, this study's results do not support a causal association between methylphenidate treatment and suicide attempts.
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