Efficacy and Safety of Scopolamine Compared to Placebo in Individuals with Bipolar Disorder Who are Experiencing a Depressive Episode (SCOPE-BD): Study Protocol for a Randomized Double-Blind Placebo-Controlled Trial

Abstract Background: Current treatment options for the management of depressive episodes in bipolar disorder are often sub-optimal, with some treatments either noted to be only partially effective or to require long durations of treatment prior to a therapeutic response. Therefore, pharmaco-therapeutic options that reduce depressive symptoms in a more rapid manner, might provide a viable therapeutic option for some people. Intravenous (IV) Scopolamine, a pan muscarinic antagonist has been demonstrated in a number of studies to confer a rapid antidepressant effect, albeit no study to date has exclusively evaluated its potential therapeutic effect in a cohort consisting solely of individuals with bipolar disorder.Methods: Individuals with bipolar disorder who are currently experiencing a depressive episode of at least moderate severity will be included in this study. Eligible participants will undergo a screening and placebo-run in visit, and will be randomised at visit 3 to the treatment or placebo group. Participants will receive the three blinded infusions over the course of two weeks, with two subsequent follow-up visits, one and three weeks after the last infusion visit. The total duration of the study will be approximately six weeks. Patients will continue their regular treatment regime in addition to study medication. Objective and subjective mood questionnaires, cognitive assessments and other psychometric instruments will be administered and recorded.Discussion: To our knowledge, this is the first study to investigate the antidepressant effects of IV scopolamine in an exclusively bipolar disorder cohort. Trial findings will contribute to the evidence base regarding the cholinergic hypothesis of mood disorders and specifically might result in an additional safe therapeutic option for the management of depressive episodes in bipolar disorder.Trial registration: ClinicalTrials.gov: NCT04211961EudraCT Number: 2017-003112-39