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Publication - Professor Nicky Welton

    The clinical effectiveness of sertraline in primary care and the role of depression severity and duration

    a pragmatic randomised controlled trial.


    Lewis, G, Duffy, L, Ades, T, Amos, R, Araya, R, Brabyn, S, Button, K, Churchill, R, Derrick, C, Dowrick, C, Gilbody, S, Fawsitt, C, Hollingworth, W, Jones, V, Kendrick, T, Kessler, D, Kounali, D-Z, Khan, N, Lanham, P, Pervin, J, Peters, T, Riozzie, D, Salaminios, G, Thomas, L, Welton, N, Wiles, N, Woodhouse, R & Lewis, GH, 2019, ‘The clinical effectiveness of sertraline in primary care and the role of depression severity and duration: a pragmatic randomised controlled trial.’. Lancet Psychiatry.


    Background: Depression is usually managed in primary care but most antidepressant trials are of patients from secondary care mental health services, with eligibility criteria based on
    diagnosis and severity. Antidepressants are now used in a much wider group of people than in older regulatory trials. We investigated the clinical effectiveness of sertraline in primary care
    patients with depressive symptoms ranging from mild to severe, and tested the role of severity and duration in treatment response.
    Methods: Multicentre placebo-controlled double-blind randomised trial of patients from 179 primary care surgeries in four UK sites. We included patients aged 18 to 74 who had
    depressive symptoms of any severity or duration in the past two years, where there was clinical uncertainty about the benefit of an antidepressant. This was designed to improve the generalisability of our sample to current use of antidepressants within primary care. Patients were individually randomised to sertraline 100mg daily or placebo stratified by severity, duration and site. The primary outcome was depressive symptoms 6 weeks after
    randomisation, measured with Patient Health Questionnaire (PHQ-9) scores. Secondary outcomes at 2, 6 and 12 weeks were depressive symptoms and remission (PHQ-9 and BDIII), generalised anxiety symptoms (GAD-7), mental and physical health related quality of life (SF-12) and self-reported improvement.
    Trial registration: Controlled Trials ISRCTN Registry, ISRCTN 84544741; Status: closed.
    Findings: Between 01/01/2015 and 31/8/2017, 655 participants were randomised to sertraline (326) or placebo (329). Primary outcome analyses were of 550 patients (266 4
    sertraline, 284 placebo, 85% follow-up that did not differ by treatment allocation). 54% of patients met ICD-10 criteria for depression and 46% for generalised anxiety. In primary
    analyses, there was no evidence that sertraline led to a clinically meaningful reduction in depressive symptoms at 6 weeks. The mean 6-week PHQ-9 score was 7.98 (SD 5.63) in the
    sertraline group and 8.76 (SD 5.86) in placebo (5% relative reduction, 95% CI -15% to 7%; p=0.41). In secondary analyses, there was strong evidence that sertraline reduced generalised
    anxiety symptoms and led to better quality of life (mental but not physical) and self-reported improvement. There was weak evidence that depressive symptoms were reduced by sertraline
    at 12 weeks. We found no evidence that severity or duration affected response. We recorded 4 adverse events for sertraline and 3 for placebo and found no evidence that adverse events
    differed by treatment allocation.
    Interpretation: Sertraline is unlikely to reduce depressive symptoms within 6 weeks in primary care but leads to improvements in anxiety and self-rated mental health, which are
    likely to be clinically important. Our findings support the prescription of SSRI antidepressants in a wider group of participants than previously thought, including those with
    mild to moderate symptoms who do not meet diagnostic criteria for depression or generalised anxiety disorder.

    Full details in the University publications repository