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Assessment of potential cardiovascular risks of methylphenidate in comparison with sibutramine: do we need a SCOUT (trial)?

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Abstract

With the recent approval of methylphenidate (MPH) for treating attention-deficit/hyperactivity disorder (ADHD) in adults, the number of patients exposed will increase tremendously. The ongoing debate on the cardiovascular safety of MPH has triggered two large retrospective cohort studies in children and adolescents as well as in young to middle-aged adults. These studies looked into serious cardiovascular events (sudden cardiac death, acute myocardial infarction and stroke) as primary endpoints and concluded that MPH was safe after a mean duration of 2.1 years of follow-up in children and adolescents and mean duration of 0.33 years of current use in adults. The results are encouraging with respect to the short- and medium-term use of MPH. Without the inherent limitations of retrospective cohort studies, a prospective randomized, double-blind, placebo-controlled, multicenter trial in individuals stratified for cardiovascular risk factors would allow for an optimized risk assessment. With many millions of patients treated per year and drawing parallels to the lately discovered risks of sibutramine, another sympathomimetic with an overlapping mode of action and similar side effects on heart rate and blood pressure, we hypothesize that such a trial might be a dedicated risk mitigation strategy for public health. A critical assessment of cardiovascular side effects of MPH appears particularly warranted, because ADHD is associated with obesity, smoking and poor health in general. We summarize recent findings with the focus on cardiovascular risks of MPH in humans; we additionally analyze the limited number of rodent studies that have addressed cardiovascular risks of MPH.

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Acknowledgments

This review was written without any dedicated funding source.

Conflict of interest

Dr. Banaschewski served in an advisory or consultancy role for Hexal Pharma, Lilly, Medice, Novartis, PCM scientific, Shire and Viforpharma. He received conference attendance support and conference support or received speaker’s fee by Lilly, Janssen McNeil, Medice, Novartis and Shire. He is/has been involved in clinical trials conducted by Lilly, Shire & Viforpharma. The present work is unrelated to the above grants and relationships. All other authors declare that they have no conflict of interest.

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  1. Research-Unit of the Department of Child and Adolescent Psychiatry, Psychosomatics, and Psychotherapy, LVR-Klinikum Essen, University of Duisburg-Essen, IG1 Virchowstr. 171, 45147, Essen, Germany

    Jochen Antel

  2. Department of Child and Adolescent Psychiatry, Psychosomatics, and Psychotherapy, LVR-Klinikum Essen, University of Duisburg-Essen, Wickenburgstr. 21, 45147, Essen, Germany

    Özgür Albayrak & Johannes Hebebrand

  3. Institute of Pathophysiology, Center of Internal Medicine, University of Essen Medical School, Hufelandstraße 55, 45122, Essen, Germany

    Gerd Heusch

  4. Department of Child and Adolescent Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim University of Heidelberg, J 5, 68159, Mannheim, Germany

    Tobias Banaschewski

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Antel, J., Albayrak, Ö., Heusch, G. et al. Assessment of potential cardiovascular risks of methylphenidate in comparison with sibutramine: do we need a SCOUT (trial)?. Eur Arch Psychiatry Clin Neurosci 265, 233–247 (2015). https://doi.org/10.1007/s00406-014-0522-8

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