Randomised Controlled Trial of the Short-Term Effects of OROS-Methylphenidate on ADHD Symptoms and Behavioural Outcomes in Young Male Prisoners with Attention Deficit Hyperactivity Disorder (CIAO-II)

Abstract

Background: 20-30% of prisoners meet diagnostic criteria for attention-deficit/hyperactivity disorder (ADHD). Methylphenidate reduces ADHD symptoms but effects in prisoners are uncertain due to high rates of comorbid mental health and substance use disorders. We therefore estimated the efficacy of a first line medication recommended by the National Institute for Health and Care Excellence (NICE) for ADHD, Osmotic Release Oral System methylphenidate (OROS-methylphenidate), in reducing ADHD symptoms in young adult prisoners with ADHD. Methods: An 8-week parallel arm, double-blind, randomised, placebo-controlled trial of OROS-methylphenidate versus placebo in 200 male prisoners from two young offender prisons in Southeast England and Scotland. Participants aged 16-25, met DSM-5 ADHD criteria. Randomisation to OROS-methylphenidate (n=101) or placebo (n=99) was stratified by prison. Trial medication was titrated for five weeks against symptom reduction and adverse effects to a maximum daily dose of 72 mg, followed by stable dose for three weeks. Primary outcome was ADHD symptoms at 8-weeks using the investigator rated Connors Adult ADHD Rating Scale (CAARS-O). Thirteen secondary outcome measures included emotional dysregulation, mind-wandering, violent attitudes, mental health symptoms, and prison officer and educational staff ratings of behaviour and aggression. Trial registration: EudraCT Number 2015-004271-78; ISRCTN16827947. Database lock 27 th August 2019 Findings: Mean CAARS-O at 8 weeks in the OROS-methylphenidate arm was estimated to be reduced by 0.57 points relative to the Placebo arm (95% CI: -2.41 to 3.56) and non-significant. The responder rate, defined as a 20% reduction in CAARS-O scores was 48.3% for the OROS-methylphenidate arm and 47.9% for the placebo arm. No statistically significant trial arm difference were detected for any of the secondary outcomes. Mean final titrated dose was 53.8 mg in the OROS-methylphenidate arm. Interpretation: The study finds that ADHD symptoms did not respond to treatment for ADHD in young adult prisoners and does not support routine treatment with OROS-methylphenidate in this population. This does not exclude treatment in those with severe symptoms who may require treatment in prison. Further research is needed to evaluate effects of higher average dosing and adherence to treatment, multimodal treatments, and preventative interventions in the community. Trial Registration: Trial registration: EudraCT Number 2015-004271-78; ISRCTN16827947. Funding: Efficacy and Mechanism Evaluation (EME) programme (project ref: 14/23/17). Janssen Pharmaceutical Company supplied Concerta XL. Declaration of Interest: Philip Asherson reports grants and personal fees from Janssen-Cilag Ltd (High Wycombe, UK), Medice (Iserlohn, Germany), Shire/Takeda Pharmaceutical Company Ltd (Tokyo, Japan) and Flynn Pharma Ltd (Stevenage, UK); non-financial support and grants from QbTech AB (Stockholm, Sweden); personal fees from Novartis International AG (Basel, Switzerland) and Eli Lilly and Company (Indianapolis, IN, USA); and grants from Vifor Pharma Group (Villars-sur-Glâne, Switzerland), GW Pharmaceuticals (Cambridge, UK) and QbTech AB, outside the submitted work. Ylva Ginsberg has received royalties, speaker fees, reimbursement for travel costs and/or collaborated in research with Shire, Medscape [www.medscape.com/ (accessed 5 January 2021)] and Studentlitteratur AB (Lund, Sweden). Susan Young is director of Psychology Innovations Ltd (London, UK), which has received fees from Shire/Takeda, and has received fees for training in attention deficit hyperactivity disorder (ADHD) assessment tools and psychological interventions. She is a consultant at the Cognitive Centre of Canada and has received fees from the sale of psychological treatment programmes; she is also president of the UK ADHD Partnership, which received unrestricted educational grants from Shire/Takeda. Stephen Lawrie has received personal fees and research income from Janssen-Cilag, as well as personal fees from Sunovion Pharmaceuticals Inc. (Marlborough, MA, USA), in connection with work on schizophrenia (i.e., outside the submitted work). John Strang conducted research studies with the study medication being provided by the relevant pharmaceutical companies, and King’s College London has received payment of consultancy fees or honoraria for such work. However, this work does not apply to the study of ADHD nor to the type of treatment (methylphenidate). Ulrich Muller-Sedgwick received honoraria for being on an advisory board and/or speaking/delivering training for the UK Adult ADHD Network, British Association for Psychopharmacology, Takeda, Sosei Heptares (London, UK), Eli Lilly and Company, and Flynn/Medice. Ethical Approval: Ethical approval was obtained from the East of England, Essex, Research Ethics committee (ref: 16/EE/0117). Research and Development approvals were obtained from Oxleas NHS Foundation Trust and NHS Forth Valley (Ref: FV908), and additional approvals were given by HM Prison & Probation Services (England) and the Scottish Prison Service.