Research priorities for metabolic interventions in severe mental illness: results of a James Lind Alliance Priority...

People with severe mental illness have higher rates of cardiometabolic morbidity and premature mortality than the general population. Altered brain energy metabolism can contribute to psychiatric symptoms, suggesting metabolic interventions could improve mental and physical health outcomes. We aimed to identify and prioritise unanswered research questions on metabolic interventions in people with severe mental illness, co-designed with people with lived experience. We conducted a James Lind Alliance (JLA) Priority Setting Partnership involving people with lived experience of severe mental illness, carers, and health and social care professionals, following JLA methodology. Research uncertainties were gathered through an international online survey. Submissions were refined through inductive thematic synthesis; out-of-scope questions were removed and the remainder checked against an umbrella review of evidence to confirm they were unanswered. Verified questions were ranked in an interim prioritisation survey. Final consensus on the top ten priorities was reached through a structured stakeholder workshop. In the initial survey, 456 participants contributed 1439 questions reflecting stakeholder perspectives. After synthesis, 51 summary questions across 13 domains were generated; two were considered answered, leaving 49 uncertainties. An interim prioritisation survey completed by 317 participants produced a shortlist of 19 questions; these were discussed in a final workshop with 31 participants (16 lived experience or carers and 15 professionals). The top ten priorities emphasised mental health effects of dietary and lifestyle interventions, roles of weight-loss medications, mechanisms linking metabolic change to brain outcomes, and metabolic effects of psychiatric medications beyond weight gain. Eight priorities focused on mental health outcomes. Stakeholders prioritised mental health outcomes and mechanistic understanding of metabolic interventions over traditional metabolic endpoints, highlighting a disconnect between current research agendas and stakeholder priorities. These priorities provide a stakeholder-driven research agenda to inform funding, policy, and future studies aimed at improving mental and physical health in severe mental illness.