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. 2017 Oct 1;74(10):1048-1055.
doi: 10.1001/jamapsychiatry.2017.2183.

Association of Risk of Suicide Attempts With Methylphenidate Treatment

Kenneth K C Man  1   2   3   4 , David Coghill  4   5   6 , Esther W Chan  2 , Wallis C Y Lau  2 , Chris Hollis  4   7   8 , Elizabeth Liddle  4   7   8 , Tobias Banaschewski  4   9 , Suzanne McCarthy  4   10 , Antje Neubert  4   11 , Kapil Sayal  4   7   8 , Patrick Ip  1 , Martijn J Schuemie  12 , Miriam C J M Sturkenboom  3 , Edmund Sonuga-Barke  4   13 , Jan Buitelaar  4   14 , Sara Carucci  4   15 , Alessandro Zuddas  4   15 , Hanna Kovshoff  4   13 , Peter Garas  4   16 , Peter Nagy  4   16 , Sarah K Inglis  4   5   17 , Kerstin Konrad  4   18 , Alexander Häge  4   9 , Eric Rosenthal  4   19 , Ian C K Wong  1   2   4   20
Affiliations

Association of Risk of Suicide Attempts With Methylphenidate Treatment

Kenneth K C Man et al. JAMA Psychiatry. .

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.

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Conflict of interest statement

Conflict of Interest Disclosures: The research leading to these results received financial support from the European Community’s 7th Framework Programme. Dr Coghill received grants and personal fees from Shire Pharmaceutical Company and Vifor Pharma; personal fees from Janssen-Cilag, Eli Lilly, Novartis, Flynn Pharma, Medice Arzneimittel Pütter, and Oxford University Press outside the submitted work. Dr Chan received grants from Bristol-Myers Squibb; Janssen, a division of Johnson and Johnson; the Research Grants Council of Hong Kong; and the Health and Medical Research Fund of Hong Kong outside the submitted work. Prof Hollis was chair of the National Institute for Health and Clinical Excellence (NICE) psychosis and schizophrenia in children and young people ADHD Guideline Group and has been an investigator on a research grant from Shire Pharmaceutical Company to the University of Nottingham. Prof Banaschewski received personal fees from Medice Arzneimittel Pütter outside the submitted work and served in an advisory or consultancy role for Actelion, Hexal Pharma, Lilly, Medice Arzneimittel Pütter, Novartis, Oxford Outcomes, PCM Scientific, Shire Pharmaceutical Company, and Vifor Pharma. Dr McCarthy received grants from Shire Pharmaceutical Company. Dr Schuemie is a full-time employee of Janssen Research & Development and shareholder of Johnson & Johnson. Prof Sturkenboom is leading a research group that received grants for specific postauthorization safety projects from Novartis, Boehringer, GSK, and Servier, with none related to the topic of the present study. Prof Buitelaar has served as a consultant to and member of advisory boards and/or speakers’ bureaus for Janssen Cilag BV, Eli Lilly, Lundbeck, Shire Pharmaceutical Company, Roche, Medice Arzneimittel Pütter, Novartis, and Servier and received research support from Roche and Vifor Pharma. Dr Carucci collaborated within projects from the European Union (7th Framework Programme), has received personal fees from Shire Pharmaceutical Company, and collaborated as a subinvestigator in clinical trials sponsored by Shire Pharmaceutical Company and Lundbeck. Prof Zuddas has served on the advisory boards of Shire Pharmaceutical Company, AstraZeneca, EcuPharma and Angelini; has received research support from Shire Pharmaceutical Company, Vifor Pharma, Roche, Lundbeck, the European Union (7th Framework Program), and the Sardinian Health Secretariat; served on data safety monitoring boards of Otsuka and Lundbeck; and has received royalties from Giunti OS and Oxford University Press. Dr Nagy has been a member of the advisory board of Eli Lilly and has received a research grant from Shire Pharmaceutical Company. Prof Konrad received speaker fees from Shire Pharmaceutical Company and was part of an investigator-initiated trial from Vifor Pharma outside the submitted work. Dr Häge served in an advisory or consultancy role for Shire Pharmaceutical Company. Prof Wong received grants from European Union 7th Framework Programme during the conduct of the study; grants from Shire Pharmaceutical Company, Janssen-Cilag, Eli Lilly, and Pfizer Inc outside the submitted work; was a member of the NICE ADHD Guideline Group and the British Association for Psychopharmacology ADHD guideline group; and acted as an advisor to Shire Pharmaceutical Company. No other conflicts were reported.

Figures

Figure 1.
Figure 1.. Illustration of Self-controlled Case Series Study Design
aEvent can take place any time throughout the observation period; no censoring on the event date.
Figure 2.
Figure 2.. Results From the Spline-Based Self-controlled Case Series Analysis
Incidence rate ratio (IRR) of suicide attempts throughout the time before and after methylphenidate exposure. The solid line is the estimated IRR, the dashed lines indicate the 95% CI, and the blue dashed line indicates baseline IRR.
See this image and copyright information in PMC

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