Health

STOP-D (Sertraline TO prevent Post-TBI Depression)

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. Around 50% of people with a head injury will have some form of depression over the next 10 years. 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 and public involvement group (PPI) recognised the symptoms of depression and also mentioned others such as irritability, confusion, being very sensitive to noises and light. They 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.

For consent to be contacted about opportunities to participate in this study, please complete this form.

Aims

We aim to test the primary hypothesis that in patients with TBI, sertraline 100mg once a day 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) 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.

It is set in 9 Major Trauma Centres (MTC) which broadly represent the socioeconomic, geographical and ethnic diversity in TBI across England. Participants will be recruited from Major Trauma Centres.

The study population is adults (>=18 years) with mild, moderate or severe TBI who do not have PTD. Patients attending A&E with a TBI will be given information about this study. We will wait for any immediate effects of the head injury, such as memory loss, to settle. Those patients who are suitable will be invited to consent to join the study 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, and increased to 100mg once a day 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.

Impact

The findings will inform whether, and how to integrate the screening and management for depression within MTC pathways.

Co-Investigators

Dr Vanessa Raymont, University of Oxford, Department of Psychiatry
Professor Mark Wilson, Imperial College Healthcare NHS trust
Dr David Okai, South London & Maudsley NHS Foundation Trust
Mr Christos Tolias, King’s College Hospital NHS Foundation Trust
Dr Brent Elliott, East London NHS Foundation Trust
Dr Bartolomiej Matras, Central and North West London NHS Foundation Trust
Dr Chris Uff, Barts Health NHS Trust
Mr Damian Holliman, The Newcastle Upon Tyne Hospitals NHS Foundation Trust
Dr Barbara Barrett, Institute of Psychiatry, Psychology & Neuroscience, King’s College London
Professor David Taylor, South London & Maudsley NHS Foundation Trust
Mr Daniel Holsgrove, Northern Care Alliance NHS Foundation Trust
Professor Damien Longson, Greater Manchester Mental Health NHS Foundation Trust
Dr Michael Dilley, King’s College Hospital NHS Foundation Trust

Collaborators

Mr Tim Lawrence, Oxford University Hospitals NHS Foundation Trust
Dr Alex Novak, Oxford University Hospitals NHS Foundation Trust
Dr Colette Griffin, St Georges University Hospital NHS Foundation Trust
Dr Shai Betteridge, St Georges University Hospital NHS Foundation Trust
Professor Hamish McAllister-Williams, Newcastle University, Academic Psychiatry and Regional Affective Disorders Service
Dr Gayathri Venkatesan, Cumbria, Northumberland and Tyne and Wear NHS Foundation Trust
Mr Nicholas Park, Lancashire Teaching Hospitals NHS Foundation Trust

Statisticians

Professor Richard Emsley, Institute of Psychiatry, Psychology & Neuroscience, King’s College London
Dr Nicholas Beckley-Hoelscher, King’s College London