Interest of scopolamine as a treatment of major depressive disorder

Introduction. - The number of patients with depression in the world is 350 millions according to estimates. The search for new treatments, particularly in forms of resistant depression, is necessary given the growing number of patients experiencing treatment failure and resistance. Scopolamine, an anticholinergic antimuscarinic molecule, is one of the treatments under evaluation. It falls within the assumptions of cholinergic disruption of the pathophysiology of depression, at different levels (genetic, receptorial [muscarinic and glutamate receptors], hormonal, synaptic...). In 2006, a pilot study made to evaluate the role of the cholinergic system in cognitive symptoms of depression found unexpected results regarding the antidepressant effect of scopolamine in depressive patients. Since that time other studies have been conducted to evaluate the benefits of treatment with intravenous injections of scopolamine. Objective. - Our main objective was to evaluate the interest of scopolamine as an antidepressant treatment in depressed populations. Methods. - We conducted a literature review with the aim of assessing the effectiveness of treatment with scopolamine in uni- and bipolar patients with depressive symptoms. The protocol consisted of two injection blocks (each block consisting of three injections spaced fifteen minutes apart within three to five days) of active ingredient or placebo crossover. The selected patients were between 18 and 45 years and had the DSM-IV major depressive disorder or bipolar disorder criteria. Regarding the methods of measurement, the primary endpoint was the reduction in scores of the Montgomery Asberg Depression Rating Scale (MADRS) with a total response defined by a decrease of more than 50 % of the score and remission corresponding to a MADRS score < 10. Seven sessions of evaluations were performed. Results. - The published results are promising in terms of efficiency with rapid antidepressant effect, a total response rate ranging from 59-64% and a remission rate of between 37 and 55% in uni- and bipolar patients, which persists at least 15 days. The treatment was well tolerated by patients with relatively mild and transient side effects the most common being the sensation of sleepiness that was also found in the placebo group. There were no serious side effects such as heart failure or confusion. In terms of mood, there was no becoming manic or hypomanic even for bipolar patients. Conclusion. - The results are encouraging, but there is concern for the moment because of the few studies, so to date there is little data on the subject including medium and long term. (C) 2016 L'Encephale, Paris.