A multi-centre randomised controlled trial of the clinical and cost-effectiveness of sertraline in preventing depression in adults following a traumatic brain injury

RESEARCH QUESTION What is the clinical and cost-effectiveness of a selective serotonin reuptake inhibitor (SSRI) for preventing depression following traumatic brain injury? BACKGROUND Traumatic brain injury (TBI) is a disruption in the normal function of the brain caused by an external force. It is one of the most common presentations in Accident and Emergency (A&E) departments, especially in young males and older people. The prevalence rates of post TBI depression (PTD) is on average 10 times higher than the general population, and this risk emerges very soon after the injury. PTD is associated with higher rates of disability, unemployment and premature mortality, including suicide. Those most at risk of PTD are more likely to be older, to be diagnosed with a mild TBI, and have a history of depression. Yet depression is not routinely screened for at TBI presentation, and rarely treated optimally. Our patient participation group have highlighted the lack of medical attention paid to mental health issues and that many neuropsychiatric symptoms are overlooked. Preliminary findings from 2 small randomised controlled trials (RCT) suggest that initiation of a selective serotonin reuptake inhibitor (SSRI) within a few weeks of the TBI could significantly reduce the incidence of PTD. AIMS We aim to build on this evidence by testing the primary hypothesis that in patients with TBI, sertraline 100mg once a day (od) prescribed for 12 months is more effective, and more cost effective, than placebo in reducing i) depressive symptoms as measured by the Patient Health Questionnaire-9 (PHQ-9) and ii) incident rate of major depressive disorder (MDD) as measured by the Mini International Neuropsychiatric Interview (MINI), at 12 months from baseline, with interim measures at 6 and 18 months. We will also measure secondary outcomes of quality of life, employment and productivity, carer burden, other neuropsychiatric symptoms and cognitive functioning. We will seek consent for follow up over 10 years and for hospital episodes statistics (HES) data. METHODS The design is a placebo controlled double blind multi-centre RCT stratified by severity of TBI (mild versus moderate/severe) and by site. It is set in 9 Major Trauma Centres (MTC) across England which broadly represent the socioeconomic, geographical and ethnic diversity in TBI. The study population is adults (>=18 years) with mild, moderate or severe TBI who do not have PTD. Patients will be invited to participate as soon as they present and within 4 weeks of the incident. Those without capacity will also be included if they otherwise meet the study criteria. The intervention will consist of sertraline at 50mg once a day (od), and increased to 100mg od after 2 weeks (except in the older adult if it will not be tolerated) for 12 months and then stopped. The control group will receive a matched placebo using the same regimen. Patients will be seen at 2, 6, 12, 24, 52 and 78 weeks for patient monitoring and safety. A sample of n=514 are needed to observe a clinically significant 5 point difference in the PHQ-9 score taking into account 25% attrition. TIMELINE There will a 6 month set up phase, 12 months of recruitment and deliver the intervention, 18 months of follow up and 6 months analysis and dissemination. The total duration is 42 months. IMPACT Our findings will inform whether, and how to integrate the screening and management for depression within MTC pathways.