The clinical effectiveness of sertraline in primary care and the influence of depression severity and duration: a pragmatic randomised controlled trial.
Depression is usually managed in primary care. However most antidepressant trials involve patients from mental health services, and there are few large pragmatic trials of the clinical effectiveness of antidepressants in primary care. Doctors also have little specific guidance on which patients are more likely to benefit from antidepressants. We investigated the clinical effectiveness of the antidepressant sertraline in patients who presented to primary care with symptoms of depression. We also tested whether the severity and duration of depressive symptoms influenced treatment response.
We undertook a multicentre placebo-controlled double-blind randomised controlled trial of patients from 179 primary care surgeries in four UK sites. We included patients aged 18 to 74 who had presented with depressive symptoms of any severity or duration in the past two years, where there was uncertainty about the possible benefit of an antidepressant. Patients were individually randomised to 100mg daily of sertraline or identical placebo, stratified by severity, duration and site. The primary outcome was Patient Health Questionnaire (PHQ-9) score at 6 weeks. Secondary outcomes at 2, 6 and 12 weeks were depressive symptoms and remission on the PHQ-9 and BDI-II, generalised anxiety disorder symptoms (GAD-7), mental and physical health related quality of life (SF-12) and self-reported improvement.
Between 01/01/2015 and 31/8/2017, 655 patients were randomised to sertraline (326) or placebo (329). Primary outcome analyses included 550 patients (266 sertraline, 284 placebo, 85% follow-up). The mean PHQ9 score at 6 weeks was 7.98 (SD 5.63) in the sertraline group and 8.76 (SD 5.86) in placebo (5% relative reduction, 95% CI 0.85 to 1.07; p=0.40). Of the secondary outcomes, there was strong evidence that GAD-7 scores were lower in the sertraline group (GAD-7 adjusted proportional change 0.83, 95% CI 0.75 to 0.91, P < 0.001) and improved mental (but not physical) health related quality of life and self-reported improvement. There was evidence that depressive symptoms were reduced by sertraline at 12 weeks on the PHQ9 (13% relative reduction, 95% CI 0.79 to .97; p=0.014) and BDI-II (16% relative reduction, 95% CI 0.74 to .95; p=0.004). We found no evidence that severity or duration affected response.
We found limited evidence that sertraline reduced depressive symptoms for primary care patients within 6 weeks but some evidence of a reduction in depressive symptoms by 12 weeks. Sertraline reduced anxiety symptoms and improved quality of life and subjective wellbeing at 6 and 12 weeks. Our study supports the use of SSRI antidepressants in primary care, but the main initial effect is to reduce anxiety symptoms. Where there is clinical equipoise about the possible benefit of an antidepressant, anxiety symptoms such as worry and restlessness indicate an increased likelihood of benefit and support prescription of an antidepressant.