Short-term probiotic augmentation in depression treatment: study protocol for a randomised controlled trial

Background There is urgent need to develop novel augmentation options for improving inadequate response to antidepressants. Emerging evidence showed that the composition of the gut microbiota is altered in patients with depression and related to their symptoms, suggesting that restoring microbial composition may constitute a promising strategy in depression treatment. This protocol introduces a study design to test the effectiveness of a short-term probiotic augmentation therapy in patients with a current depressive episode. Methods Using a randomised, double-blind, placebo-controlled design, the effectiveness of probiotic supplementation will be examined in 60 patients with current severe depressive episodes (Hamilton Depression Rating Scale > 24). Patients will be randomly assigned either to a 4-weeks probiotic or placebo treatment. Assessments will take place at baseline (pre-intervention), at 4 weeks (post-intervention) and at 8 weeks (follow-up) of the study program. The primary study outcome will be depressive symptoms as measured with the Hamilton Depression Rating Scale (experts’ ratings), while secondary outcomes include immune signalling and inflammatory processes, hypothalamic-pituitary-adrenal axis responses, neurogenesis, the release of appetite-regulating hormones, the composition of gut microbiota, sleep quality, physical activity and multimodal neuroimaging. Discussion In search for augmentation strategies in depression treatment, this protocol describes a study design to test the effectiveness of a short-term probiotic augmentation therapy in patients with major depressive disorders. We also suggest the assessment of comprehensive secondary outcomes to determine biomarkers for personalized treatment responses and the development of more efficient microbial interventions in major depressive disorders.