A randomised controlled trial to evaluate 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

Background: Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder involving inattention, hyperactivity and impulsivity, which 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 in people with severe mental illness (SMI) such as bipolar disorder (bipolar) and psychosis. There is substantial uncertainty over the effectiveness of stimulant and non-stimulant medication in adult ADHD comorbid with SMI. There is also concern that they could trigger or worsen psychotic or manic symptoms. Whilst National Institute of Health and Care Evidence (NICE) ADHD guidelines indicate available evidence does not justify a deviation from their main recommendations of using stimulants first line, this is based on limited studies within this comorbid population. A randomised controlled trial (RCT) is needed to address this evidence gap. We present a protocol for a pragmatic, observer-blind, multi-centre, two-arm, RCT called SNAPPER that aims to investigate the clinical and cost-effectiveness of stimulant compared with non-stimulant medication for adults with ADHD and a history of SMI.

Methods: The recruitment target is 244 participants, aged 18 years or above, who have a history of SMI (either bipolar disorder or psychosis) with ADHD. Having provided informed consent for screening, participants will undergo validated diagnostic screening assessments to re-confirm the diagnosis of bipolar or psychosis and confirm an ADHD diagnosis. Those with confirmed diagnoses will provide informed consent for entry to the main trial and will then be randomised to receive either stimulant (lisdexamfetamine) or non-stimulant (atomoxetine) medication. The primary outcome measure is observer-rated ADHD symptom severity at 6 months. Secondary outcomes include ADHD symptom severity at 12 months, emergence of symptoms of bipolar or psychosis, health-related quality of life, occupational, daily functioning, substance misuse, cost-effectiveness, adherence, concomitant medication and process outcomes at 6 and 12 months.

Discussion: Given that untreated ADHD is associated with poor clinical outcomes, unemployment and criminal justice system involvement, clear evidence in this area is likely to improve recovery for individuals with ADHD and a history of SMI, reducing costs for the individual, the NHS and society.

Trial registration: ISRCTN79796233. Registered on 19/05/2022. https://www.isrctn.com/ISRCTN79796233.