Title: Stimulant Medication for ADHD and Tics - Understanding Response versus Non-stimulants (SATURN study): a randomised trial of the clinical and cost-effectiveness of methylphenidate versus guanfacine for ADHD in children and young people with a co-existing tic disorder
Funder: Department of Health and Social Care

Abstract: BACKGROUND_x000D_ _x000D_ Around 3-5% of children and adolescents have attention deficit hyperactivity disorder (ADHD). Young people with ADHD find that they struggle to pay attention, have higher than usual levels of energy and their behaviour can be impulsive or unpredictable. This can lead to a young person with ADHD having difficulties at school or keeping a job. It may also result in them looking to drugs, alcohol, other substances, crime and anti-social behaviour as an expression of how they are feeling. This can lead to further mental health struggles such as anxiety and depression._x000D_ _x000D_ Around 1 in 5 young people with ADHD also experience ‘tics’, which consist of uncontrolled, sudden movements of the body and sounds. This may sometimes lead to the person feeling embarrassed, isolated, and hopeless and bullied by others. These feelings can sometimes result in self-harm and the person may start to experience more mental health struggles._x000D_ _x000D_ Early treatment is crucial to help the person cope and reduce the burden on the family and wider social and healthcare systems. Medication for ADHD is highly effective and the clinically recommended first-choice medication is methylphenidate, which is a stimulant. However, there is concern amongst clinicians that using stimulant medication to treat young people with both ADHD and tics may make the young person’s tics worse. As a result of this, many clinicians prefer to prescribe non-stimulant medication, which may not be as effective for treating the ADHD symptoms._x000D_ _x000D_ AIM_x000D_ _x000D_ The aim of this research is to understand whether stimulant or non-stimulant medication is most effective for treating children and young people who are experiencing both ADHD and tics._x000D_ _x000D_ METHODS_x000D_ _x000D_ We will conduct a research trial to compare stimulant medication (methylphenidate) with non-stimulant (guanfacine). Both types of medication are recommended for the treatment of ADHD. We will recruit 314 young people aged 6-17 years old who have been diagnosed with ADHD and who also experience mild to moderate tics. Half of the young people in the study will be prescribed the stimulant medication (methylphenidate) and half will be prescribed the non-stimulant (guanfacine). Which treatment they get will be randomly decided so that the treatments can be compared. The young people will be asked to stay on their allocated medication for 12 months. However, they will be able to change or stop taking the allocated medication at any point if they, their parents or their doctors decide this would be best for them._x000D_ _x000D_ The young people and their parents will be asked to complete research questionnaires before they start treatment (baseline) and then after 3 and 12 months (follow-up). The families will be invited to attend the clinic for their first appointment (before they start treatment) but all other questionnaires will be completed by talking to a project researcher over the phone or by video-conferencing. _x000D_ _x000D_ This study will be carried out by a highly experienced team. The team will work closely with young people experiencing ADHD and tics and their families to ensure that the research is designed in the best way possible to ensure that young people and their families want to, and are able to take part._x000D_ _x000D_ The findings will provide high-quality evidence to inform updates of the NICE (National Institute for Health and Care Excellence) ADHD guidelines which help clinicians provide the best quality care for young people with ADHD.

Lay abstract: RESEARCH QUESTION _x000D_ _x000D_ What is the clinical and cost-effectiveness of stimulant compared with non-stimulant medication for children and young people (CYP) with ADHD and co-existing tics?_x000D_ _x000D_ BACKGROUND_x000D_ _x000D_ Around 3-5% of CYP have attention deficit hyperactivity disorder (ADHD) and around 1 in 5 of these will also experience chronic ‘tics’, which consist of uncontrolled, sudden movements of the body and sounds. Early treatment is crucial to help the person cope and reduce the impact on the family and wider social and healthcare systems. Medication for ADHD is highly effective and the clinically recommended first-line medication is methylphenidate, which is a stimulant. However, there is concern amongst clinicians that using stimulant medication to treat young people with ADHD and tics may make the young person’s tics worse. As a result of this, many clinicians prefer to prescribe non-stimulant medication, which may not be as effective for treating the ADHD symptoms._x000D_ _x000D_ AIMS AND OBJECTIVES_x000D_ _x000D_ The aim of this research is to understand whether stimulant or non-stimulant medication is most effective for treating children and young people who are experiencing both ADHD and tics.ADHD symptoms and tics are joint primary outcomes; therefore, the trial is powered for both outcomes. We aim to test whether stimulant compared with non-stimulant medication is:_x000D_ a) superior for ADHD symptoms: stimulants should result in a clinically important improvement in ADHD symptoms._x000D_ b) non-inferior for tics: stimulants should not result in a clinically important worsening with respect to tics._x000D_ _x000D_ _x000D_ METHODS_x000D_ _x000D_ Design: Two-arm parallel group randomised comparative trial. The co-primary outcomes (ADHD symptoms and tics) will be measured at 12 weeks. The treatment period is 12 months. Anyone wishing to stop or change their allocated medication will be free to do so with any changes recorded. All participants, whether persisting with allocated medication or not, will be followed up for 12 months unless they withdraw consent. Participants' medication will be monitored by the trial team for the 12-month duration._x000D_ _x000D_ Setting: NHS CAMHS and community paediatric clinics in England. _x000D_ _x000D_ Study population: CYP with ADHD and co-existing tics._x000D_ _x000D_ Sample size: 314 participants (157 per arm), recruited over 24 months from 3 regional Hubs across England._x000D_ _x000D_ Randomisation: Eligible patients who consent (age under 16: parental consent, young person’s assent; age 16-17: young person’s consent) will be allocated on 1:1 ratio to receive either stimulant (modified-release methylphenidate) or non-stimulant medication (guanfacine). Randomisation will be stratified by site._x000D_ _x000D_ TIMELINES FOR DELIVERY_x000D_ _x000D_ Month (M) 1-8: Protocol development, approvals by Medicines and Healthcare products Regulatory Agency (MHRA), database development, site set-up and training._x000D_ M 9-18: Internal pilot recruitment._x000D_ M19: Internal pilot progression review by Trial Steering Committee (TSC)/ Data Monitoring and Ethics Committee (DMEC) and report to sponsor & funder._x000D_ M 20-32: Complete recruitment, target average 15 patients/month, 3 hubs across England._x000D_ M 20-44: 12-month follow-up completed (First Person Last Visit – Last Person Last Visit)._x000D_ M45: Final data cleaning and data lock._x000D_ M 45-50: Analysis and write-up of results._x000D_ M 50: Final Report submission._x000D_ _x000D_ ANTICIPATED IMPACT AND DISSEMINATION_x000D_ _x000D_ This research will result in high impact peer-reviewed publications, including a full report in the NIHR HTA Journal. We anticipate that results will support a NICE ADHD Evidence Update as the HTA 18/116 call was in response to a NICE research recommendation (NG87 [15]). We will present the findings at national and international conferences, as well as service user/ voluntary sector organisations. We will hold events for NHS providers, commissioners and clinicians.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: MENTAL HEALTH