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New Formulations of Methylphenidate for the Treatment of Attention-Deficit/Hyperactivity Disorder: Pharmacokinetics, Efficacy, and Tolerability

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Abstract

Psychostimulants are the recommended first-line pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD). Methylphenidate is one of the most commonly used psychostimulants worldwide. Given that immediate-release and/or tablet/capsule formulations may decrease adherence to methylphenidate treatment, several drug companies have been developing novel long-acting and/or liquid/chewable formulations that may improve adherence as well as (for long-acting formulations) reduce abuse potential, decrease stigma associated with multiple administrations per day, and decrease the potential for adverse effects related to dosage peak. Here, we review the pharmacokinetics, efficacy, and tolerability of novel formulations of methylphenidate that are in development or have been approved by the US FDA or European Medicines Agency (EMA) in the last 5 years. We searched the websites of the FDA, EMA, ClinicalTrials.gov, and the pertinent drug companies. We also searched PubMed, Ovid databases (MEDLINE, PsycINFO, Embase + Embase classic), and ISI Web of Knowledge (Web of Science [Science Citation Index Expanded], Biological Abstracts, Biosis, Food Science and Technology Abstracts) to retrieve any additional pertinent information. We found data from trials for the following compounds: (1) methylphenidate extended-release oral suspension (MEROS; NWP06, Quillivant™); (2) methylphenidate extended-release chewable capsules (NWP09, QuilliChew ER™); (3) methylphenidate hydrochloride extended-release capsules (Aptensio XR™); (4) methylphenidate extended-release orally disintegrating tablets (XR-ODT; NT-0102, Cotempla™); (5) ORADUR technology (once-daily tamper-resistant formulation) methylphenidate sustained release (SR); and (6) methylphenidate modified-release (HLD-200; Bejorna™). Overall, available evidence based on trials suggests these compounds have good efficacy and tolerability. Future research should further explore the effectiveness and tolerability of these new formulations as well as their potential to improve adherence to treatment in the ‘real world’ via pragmatic trials.

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Authors and Affiliations

  1. Academic Unit of Psychology, Department of Psychology, Developmental Brain-Behaviour Laboratory, University of Southampton, Building 44 Highfield Campus, Clinical and Experimental Sciences (CNS and Psychiatry) and Solent NHS Trust, Southampton, SO17 1BJ, UK

    Samuele Cortese

  2. New York University Child Study Center, One Park Ave, 7th floor, New York, NY, 10016, USA

    Samuele Cortese

  3. IRCCS Stella Maris, Scientific Institute of Child Neurology and Psychiatry, Viale del Tirreno 331, 56128, Calambrone, Italy

    Giulia D’Acunto & Gabriele Masi

  4. Pediatric Sleep Center, Hospital Robert Debré, 48 Bd Sérurier, 75019, Paris, France

    Eric Konofal

  5. NLS-Pharma, Breitenweg 10, 6370, Stans, NW, Switzerland

    Eric Konofal

  6. Division of Child and Adolescent Neuropsychiatry, University of Turin, Piazza Polonia 94, 10126, Turin, Italy

    Benedetto Vitiello

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  1. Samuele Cortese
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  2. Giulia D’Acunto
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Correspondence to Samuele Cortese.

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Conflict of interest

Dr. Cortese has received honoraria from the Association of Child and Adolescent Mental Health (ACAMH), UK, and royalties from Aargon Healthcare, Italy, for online educational activity on ADHD. Dr. D’Acunto has no competing conflicts of interest. Dr. Konofal is on the speakers’ bureau of Shire and is an employee of NLS-Pharma. Dr. Masi has received grants from Eli Lilly and Shire; consulting fees/honoraria from Eli Lilly, Shire, and Angelini; and payments for lectures from Eli Lilly, Shire, Lundbeck, and Otsuka. Dr. Vitiello has no competing conflicts of interest. The authors have no conflicts of interest specifically related to this paper.

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Cortese, S., D’Acunto, G., Konofal, E. et al. New Formulations of Methylphenidate for the Treatment of Attention-Deficit/Hyperactivity Disorder: Pharmacokinetics, Efficacy, and Tolerability. CNS Drugs 31, 149–160 (2017). https://doi.org/10.1007/s40263-017-0409-0

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