EASE: Evaluating Antidepressants for emotionaliSm after strokE: A multi-centre, randomised, double-blind, placebo-controlled trial to establish the effect(s) of administration of sertraline (50 mg once daily for Six Months) in people with a recent stroke and post-stroke emotionalism

Research question: What is the clinical and cost-effectiveness of sertraline for post-stroke emotionalism (PSE)? Background: PSE is common, distressing and socially disabling. Finding effective treatments for mental health and emotional problems after stroke is a research priority. A 2019 Cochrane review concluded antidepressants may reduce PSE frequency and severity, but that the quality of evidence is very low and insufficient for practice recommendations. Two of the seven trials in the review were of sertraline which NICE recommends can be used by people with chronic health problems and multiple co-morbidities or polypharmacy. There are no new, ongoing or recently completed trials of antidepressant interventions to treat PSE. Aims and objectives: To determine if administration of sertraline 50mg OD for 6 months in the first year after stroke reduces PSE symptoms in adults. Methods: Multi-centre, parallel-group, 1:1 securely randomised, double-blind, placebo-controlled trial to determine the effectiveness and cost-effectiveness of sertraline in people with PSE. There will be an internal pilot to confirm that recruitment, retention and collection of outcome data will allow successful trial delivery. Target population: 310 adults with stroke in previous year and PSE symptoms, giving 264 participants with primary outcome data, providing 90% power at two-side 5% significance level to detect a difference between groups of 0.4 standard deviations, assuming 15% drop out. Intervention: 50mg sertraline, OD for 6-months. The decision to evaluate sertraline was based on review of the evidence and consultation with stroke clinicians, psychiatrists, general practitioners, and PPIE contributors, who considered the benefits and risks of sertraline over alternative antidepressants. Comparator: Identical placebo tablets. Randomisation: Randomly assigned in a 1:1 ratio using stratification to achieve balance between treatment groups on time since stroke (0-6 months, 6-12 months), depression severity (PHQ-9 score =10 vs <10), prescription of any antidepressant in past one year. Primary outcome: Difference between sertraline and placebo groups in change of symptoms of PSE, measured by the Center for Neurologic Studies-Lability Scale (CNS-LS) between baseline and 6-months. Safety measures: We will monitor for Serious Adverse Reactions and identify whether their frequency is greater than in other populations receiving sertraline and sufficiently common to offset treatment benefits. Centralised screening/outcome assessment: Following database searches, pre-trained CTU RAs will virtual/telephone screen interested individuals for PSE using CNS-LS. If score = 13, then the person will be referred to nearest participating local NHS recruiting site to confirm trial eligibility, complete consent and baseline assessments will be administered. Opportunistic recruitment will also be progressed at NHS recruitment sites. Timelines for delivery: 5 years. Start June 1st 2023, 6-months set up, 30-months recruitment, 12-months follow up (6-months on drug, 6-months off), 6-months close out. To recruit and follow-up at least 310 people over 2 years, 25+ centres required. Anticipated impact and dissemination: Resolve current uncertainty around using sertraline to treat PSE. Positive results will indicate a safe and effective PSE treatment. Neutral results, or finding major safety issues, will be of direct relevance to people with PSE globally and important for their care.