Title: Randomised controlled trial of the short term effects of OROS-methylphenidate on ADHD symptoms and behavioral outcomes in young male prisoners with attention-deficit/hyperactivity disorder
Funder: Department of Health and Social Care

Abstract: We propose an 8-week randomised placebo controlled trial of OROS-MPH in young prisoners meeting symptom criteria for ADHD. The study will be conducted at HMYOI Polmont (ages 16-21), HMYOI Isis (ages 18-25) and HMP/YOI Rochester (ages 16-25). Primary hypothesis is that OROS-MPH compared to placebo reduces ADHD symptoms in young offenders meeting diagnostic criteria for ADHD. Secondary hypotheses evaluate improvements in function and behaviour and whether these improvements are mediated by reductions in ADHD symptoms. The primary research question is critical because many other states, besides ADHD, are associated with inattentive, restless and impulsive behaviour in forensic populations (e.g. personality disorder, anxiety, post-traumatic stress and substance misuse). It remains unknown whether offenders meeting symptom criteria for ADHD show the same clinical response to OROS-MPH reported in community samples. Currently, ADHD is rarely treated in offender populations because of concerns about the efficacy and safety of OROS-MPH or other strimulant medications in prisoners. Participants will be 200 male prisoners meeting DSM-5 criteria for ADHD. The primary outcome will be investigator rated ADHD symptoms. Secondary outcomes will be emotional dysregulation (anger, temper and emotional volatility), attitude towards violence (a predictor of violent behaviour), number of antisocial incidents recorded by prison staff and number of positive Incentives and Earned Privileges (reflecting positive engagement with rehabilitation/education program). Participants aged 16-25 will have at least 4 months sentence remaining. Exclusion criteria include current treatment for ADHD and history of major mental illness (e.g. schizophrenia, bipolar I disorder). Following the same procedures as our current feasibility study, prisoners will be screened for ADHD using a self-rated ADHD rating scale. Screen positive cases will complete the Diagnostic Interview for Adult ADHD (DIVA) followed by a developmental and psychiatric assessment by a clinician trained in the diagnosis of ADHD. Medication will be titrated from 18-72mg in weeks 1-5 to maximise control of ADHD symptoms and minimise adverse effects. Endpoint measures will be completed after 8 weeks. Power calculation is based on data from an open-label pre-post study using similar procedures. We observed an average 46% decline in ADHD symptoms. Assuming that 20% of the effect is due to OROS-MPH, the study is powered to detect an effect of d=0.55, consistent with the average effect size from meta-analyses of MPH studies in adult ADHD. Assuming a maximum 25% loss to follow-up, a sample of 100 is required in each arm for >90% power at an alpha of 0.05. In the pilot, loss at random resulted from unexpected release or prison transfers, unrelated to change in recent behaviour. Assuming a 50% lower recruitment rate in a placebo controlled trial, pilot data suggests 3% of the screened population in ISIS, 5% in Polmont and 3-5% in Rochester, will enter the trial. With an initial cohort of 1557 subjects plus 40 new prisoners a month in Polmont, 110 in ISIS and 30 in Rochester, we envisage completing recruitment within 30 months. Economic benefits are expected from reduced prison costs and fewer interventions for injuries and clinical impairments (e.g. emotional instability, restlessness, sleep problems). Long term savings are envisaged from reduced recidivism, mental health comorbidities and greater social integration.

Lay abstract: We propose a placebo controlled trial of the effects of a once daily formulation of methylphenidate (OROS-MPH) on ADHD symptoms in young prisoners meeting ADHD criteria. ADHD is a common child onset neurodevelopmental disorder characterised by impairing inattentive, overactive and impulsive behaviours; symptoms that overlap with and could be explained by other common mental health disorders seen in offenders. ADHD persists in adults causing impairment in 65% of cases at age 25. Adverse outcomes that improve with treatment include clinical (e.g. ADHD symptoms, emotional dysregulation) and psychosocial (e.g. educational failure, unemployment, dangerous driving, antisocial behaviour) problems. Methylphenidate (MPH) is the first line treatment recommended for ADHD with severe impairment in the UK. A particular concern for ADHD children is the high risk for developing antisocial behaviour during adolescence and young adulthood. Systematic review concludes that 30% of adolescent and 26% of adult prisoners have ADHD. Epidemiological data from Sweden showed a 32% reduction in criminal conviction rates among men with ADHD during periods of drug treatment for ADHD. Despite known effects of MPH on ADHD symptoms, it is uncommon to diagnose and treat ADHD in prisoners. The reason is uncertainty over the effects of MPH on ADHD in forensic populations, since inattentive, restless and impulsive states may also reflect personality disorder, anxiety, post-traumatic stress and substance abuse. NICE therefore recommend that controlled trials are conducted to test the efficacy of MPH against ADHD symptoms in forensic populations. To address this problem we propose an 8-week randomised placebo controlled trial of OROS-MPH on ADHD symptoms and behaviour in 200 prisoners meeting criteria for ADHD. Participants from Young Offender Institutes and prisons (Polmont, Falkirk; Isis, London; Rochester, Kent) will meet DSM-5 criteria for ADHD. Polmont is Scotland’s national holding facility for offenders aged 16-21; Isis is the holding prison for offenders aged 18-25 offenders in London; Rochester is a holding prison and young offender prison in Kent. The study builds on a pilot study in HMP Isis led by the chief investigator that follows the same procedures proposed for this study; but was a pre-post open study with no control group. The pilot study showed significant improvements for all key outcomes included in this study. In addition to ADHD, we saw improvements in emotional dysregulation, antisocial behaviour, attitudes towards violence and the number of Incentives and Earned Privileges (indicating positive engagement with education, occupant and rehabilitation). 20% of prisoners met DSM-5 diagnostic criteria for ADHD, of which 70% had one or more recorded antisocial incidents in the previous 2 months. The team brings together leading academic clinicians with expertise in ADHD, the criminal justice system and offender mental health. A key outcome will be the demonstration that MPH significantly reduces ADHD symptoms and antisocial behaviour and improves engagement with the rehabilitation process in young prisoners. This study is required for development of cost-effective ADHD offender healthcare pathways and is supported by a collaborative network of offender mental health teams and advice from public and patient groups, including prison offender management and healthcare staff in daily contact with prisoners.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: MENTAL HEALTH