Several lines of evidence suggest that acetylcholine has a role in the etiology of depression. The administration of physostigmine, an inhibitor of cholinesterase, can exacerbate depression, and patients with depression experience exaggerated polysomnographic findings and pupillary responses following administration of cholinergic medications. These findings suggest that anticholinergic medications may improve depression, but a controlled study of the anticholinergic medication biperiden failed to demonstrate a significant benefit of therapy.

In the current study, the authors report on the efficacy of scopolamine in the management of depression and bipolar disorder. The study began as an investigation of the effect of anticholinergic treatment on cognition in depression, but the authors designed a randomized, crossover trial after noting an improvement of depression scores associated with scopolamine.