Title: The clinical and cost-effectiveness of Stimulant compared with Non-stimulant medication for adults with Attention-deficit / hyperactivity disorder and a history of Psychosis or biPolar disordER: SNAPPER
Funder: Department of Health and Social Care

Abstract: Attention-Deficit/Hyperactivity Disorder (ADHD) is a common mental disorder that involves problems with attention, overactivity and acting impulsively. Mood swings are also common. ADHD starts in childhood and frequently persists into adulthood. Medication is the mainstay of treatment for ADHD in adults. There are two types of medication: stimulants, which are recommended to be used first, or non-stimulants._x000D_ _x000D_ ADHD in adults commonly occurs alongside bipolar disorder (bipolar) or psychosis, both severe mental illnesses. Experts are concerned and uncertain about how effective and safe medications for ADHD are in people who also have psychosis or bipolar. Currently, there is little evidence to guide clinicians and patients in making a choice about which medication for ADHD is best in this situation. _x000D_ _x000D_ We will conduct a study to address this evidence gap. Its main aim is to understand how effective stimulant compared with non-stimulant medication is for adults with ADHD and a history of psychosis or bipolar. The study will also evaluate how safe the medications are, and address whether stimulants or non-stimulants represent better value for money for the NHS._x000D_ _x000D_ The design of the study is called a “randomised controlled trial”, which is the best way to find out the answer to this type of scientific problem. We will recruit 324 adults with ADHD and psychosis and 324 people with ADHD and bipolar and compare the use of stimulant and non-stimulant medications in each of these groups. The total sample of 648 adults will be recruited mostly from secondary mental health services such as community mental health teams and other secondary care services, as well as specialist ADHD teams. Whether participants in the trial are asked to take stimulant or non-stimulant medication will be decided by random chance. The participants' psychiatrists will carefully assess them at least every two weeks at first, to see if the medication is working, whether they are on the right dose, and for side effects. Researchers will complete questionnaire assessments immediately after people have agreed to take part in the study, and then 6 and 12 months later. These questionnaires will measure ADHD symptoms, day-to-day functioning, quality of life, use of health services, and mood swings. How far new symptoms of psychosis or bipolar emerge will be measured at 3, 6, 9 and 12 months. Other than this the patients' care will not change. The study will take 58 months to complete._x000D_ _x000D_ A person with lived experience of bipolar is part of the research team. We have also held two consultation events with people with lived experience of mental health problems in Birmingham, including people with experience of ADHD, and explained the intended study to obtain their views. Opinions expressed have helped us mould this study in crucial ways, including what is important to measure and when. We will form a live experience advisory panel made up of people with lived experience of ADHD and/or bipolar or psychosis and their family/partners who will meet every 6 months to advise on ongoing aspects of the study. People with lived experience will also be on the high-level Trial Steering Committee throughout the research. We will develop a plan to disseminate the results of the study through open access articles, conference presentations, public engagement events, clinical workshops, as well as an end of study event.

Lay abstract: Background: Attention-Deficit/Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder involving inattention, hyperactivity and impulsivity that starts in childhood and frequently persists into adulthood. Stimulant and non-stimulant medication are the mainstay of treatment in adults. ADHD in adults is commonly comorbid with bipolar disorder (bipolar) and psychosis. There is substantial uncertainty over the effectiveness of stimulant and non-stimulant medication in adults with ADHD and comorbid psychosis or bipolar. There is also concern that they could trigger psychotic or manic symptoms. A randomised controlled trial (RCT) is needed to address this evidence gap._x000D_ _x000D_ Aims and Objectives: The aim of the study is to evaluate the clinical and cost-effectiveness of stimulant compared with non-stimulant medication for adults with ADHD and a history of either psychosis or bipolar._x000D_ _x000D_ Primary objective: To evaluate separately in adults with 1) ADHD and a history of psychosis and 2) ADHD and a history of bipolar, whether stimulant vs. non-stimulant medication reduces ADHD symptom severity at 12 months._x000D_ _x000D_ Secondary objectives: To evaluate separately in adults with 1) ADHD and a history of psychosis and 2) ADHD and a history of bipolar the impact of stimulant vs. non-stimulant medication: a] on ADHD symptom severity at 6 months; b] on the emergence of symptoms of bipolar or psychosis over 12 months; c] on health-related quality of life, occupational, functional, substance misuse and other outcomes at 6 and 12 months; d] on cost-effectiveness_x000D_ _x000D_ Methods: We will complete a pragmatic, observer-blind, multi-centre, stratified, 2-arm, parallel group, RCT comparing Lisdexamfetamine (stimulant) with Atomoxetine (non-stimulant). Strata are defined according to a history of: (1) bipolar or (2) psychosis. 648 participants will be recruited in total, meaning there will be 324 participants with ADHD and bipolar, and 324 with ADHD and psychosis. We include an internal pilot with clear progression criteria that will be independently assessed for each stratum. Participants will be recruited from mental health Trusts / Health Boards in the Midlands, London and South East, the North East and Scotland. A PPI co-applicant and lived experience advisory panel will aid the study throughout. The analysis will be on an intention to treat basis and use ADHD symptoms measured at 12 months post-randomisation as the primary outcome. The primary analysis of all outcomes will be based on the separate treatment effects for each stratum. A health economic trial-based analysis of the cost-effectiveness of Lisdexamfetamine vs. Atomoxetine medication will be undertaken for each stratum. The trial will take 58 months to complete._x000D_ _x000D_ Impact: We will provide definitive evidence as to the clinical and cost-effectiveness of Lisdexamfetamine vs. Atomoxetine in the treatment of adults with ADHD and a history of psychosis or bipolar, as well as the risks of adverse events associated with each medication. The results will provide clear guidance to NICE, clinicians and service users. Given that untreated ADHD is associated with poor clinical outcomes, unemployment and criminal justice system involvement, clear effectiveness evidence in this area is likely to improve recovery for individuals with ADHD and a history of psychosis or bipolar, reduce costs for the individual, the NHS and society

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: MENTAL HEALTH