Investigating Scopolamine's cognitive effects and therapeutic potential in bipolar disorder

Background: Bipolar disorder is a severe psychiatric condition characterised by mood dysregulation, with existing treatments often limited by delayed effects and suboptimal efficacy. Scopolamine, a muscarinic cholinergic antagonist, has emerged as a potential rapid-acting antidepressant for depressive episodes in bipolar disorder. Its effects on cognition and safety profile in bipolar disorder, however, remain poorly understood. Methods: This thesis comprises a series of studies, including a systematic review and meta-analysis, a randomised controlled trial, and an extensive safety evaluation. The systematic review assessed the cognitive impacts of scopolamine across various doses and routes of administration in healthy volunteers. The SCOPE-BD trial evaluated the antidepressant efficacy and safety of intravenous scopolamine versus placebo in individuals with bipolar disorder during depressive episodes. Safety profiles were detailed through adverse event monitoring and analysis of vital signs. Results: The systematic review indicated that scopolamine generally impairs memory and attention, with injectable routes showing more pronounced effects. In the SCOPE-BD trial, scopolamine did not demonstrate any significant antidepressant efficacy compared to placebo. Safety evaluations highlighted a manageable adverse event profile, though vigilance for anticholinergic effects remains critical. Discussion: Despite the absence of significant antidepressant effects in the SCOPE-BD trial, the safety profile of scopolamine was within acceptable limits, supporting its continued investigation under careful monitoring. The cognitive impairments noted in healthy volunteers warrant cautious consideration of scopolamine’s use, emphasising the need for further research to explore its mechanistic actions and potential therapeutic roles. Conclusion: Although the SCOPE-BD trial did not find antidepressant efficacy of intravenous scopolamine, future research should focus on selectively modulating muscarinic M2- and M4-receptors to enhance scopolamine's antidepressant efficacy while minimising cognitive impacts. These efforts could tailor scopolamine-based treatments to individual neurobiological profiles, improving therapeutic outcomes in mood disorders.

Publisher

University of Galway

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CC BY-NC-ND

cbn

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University of Galway Theses (PhD Theses)