View clinical trials related to Severe Depression.
Filter by:Recent research demonstrates that the composition of the gut microbiome is a master regulator of key neurophysiological processes that are affected in depression. Indeed, contemporary studies showed that faecal microbiota is altered in patients with major depressive disorder (MDD). Furthermore, it has also been shown that supplementation of probiotics ameliorated depressive symptoms in unmedicated patients with mild to moderate depression. However, no study has yet explored the efficacy of a probiotic-based therapy in patients with severe MDD in addition to a standard antidepressant treatment. As dietary and lifestyle interventions may be a desirable, effective, pragmatical and non-stigmatizing prevention and adjuvant therapy (in addition to antidepressant treatment) in depression, this project is aimed at investigating for the first time if probiotic supplementation compared to a placebo treatment improves the effect of standard antidepressant medication on depressive symptoms (i.e. better and faster remission) in patients with severe MDD. Furthermore, this study will further test if probiotic supplementation modulates immune signalling and inflammatory processes (macrophage migration inhibitory factor and interleukin 1 beta), hypothalamic-pituitaryadrenal (HPA) axis responses (saliva cortisol), neurogenesis (brain-derived neurotrophic factor (BDNF) expression), the release of appetite-regulating hormones (leptin and ghrelin), the composition of gut microbiota (in particular levels of Enterobacteriaceae, Alistipes and Faecalibacterium) and brain perfusion, structure and activation and if these changes are associated with the probiotic-induced effect on depressive symptoms.
Electroconvulsive therapy (ECT) is a non-pharmacological treatment used in resistant depression whose effectiveness has been demonstrated. However, the brain mechanisms underlying this therapeutic effect remain unclear. Many animal studies show a neurotrophic action of ECT on the hippocampus: increased neurogenesis, synaptogenesis, proliferation of glial cells. In addition, functional imaging of "resting state" type have shown, among depressed patients after ECT, increased functional connectivity . These results were reinforced by the recent work of Perrin (2012). In view of this a priori contradictory, it seems appropriate to continue research neuroanatomical correlates subtending neurofunctional processes responsible at the same time improving the clinical depressive. The investigators suggest using an original technique never used in this type of population: Functional magnetic resonance imaging (fMRI) or multimodal structural-functional. This method will allow us to study the impact of ECT on brain structures involved in major depressive disorder: hippocampus.
In this proof of concept study, the investigators plan to administer iv ketamine interleaved with ECT days. Patients with treatment resistant depression who are deemed to be eligible for ECT treatment will randomly be assigned to either ketamine or active placebo.