Antidepressant efficacy and safety of scopolamine in individuals with bipolar disorder (SCOPE-BD): A randomized double-blind placebo-controlled trial.

BACKGROUND

Current treatments for depressive episodes in bipolar disorder are often limited by partial efficacy or delayed therapeutic response. Intravenous scopolamine, a pan-muscarinic antagonist, has shown rapid antidepressant effects in some studies; however, its efficacy in individuals with bipolar disorder remains undetermined (ClinicalTrials.gov Identifier: NCT04211961).

METHODS

Individuals with bipolar disorder experiencing a depressive episode of at least moderate severity (n = 50) were randomized to receive either 4 μg/kg intravenous scopolamine or saline placebo on three occasions, with two follow-up visits over approximately five weeks. The primary outcome included change in depressive symptoms (Hamilton Depression Rating Scale). Secondary outcomes included subjective and objective affective symptoms, global functioning, safety metrics, and adverse events with generalized linear mixed-effects models employed.

RESULTS

Both groups exhibited reductions in depressive symptoms over time; however, scopolamine did not result in significantly greater improvement compared to placebo (β = -0.60, 95 % CI [-15, 14]). Secondary outcomes, including treatment response, remission rates, and global functioning, showed no differences between groups. Scopolamine was associated with milder adverse events, including dizziness and dry mouth, but no significant differences in moderate or severe events relative to placebo.

CONCLUSIONS

This is the first study to examine the antidepressant effects of intravenous scopolamine in an exclusively bipolar disorder cohort. These findings suggest scopolamine is safe but does not demonstrate efficacy over placebo. The lack of significant effect highlights the need for further research examining the precise role of the muscarinic-cholinergic system. Trials of intravenous scopolamine in mood disorders should currently be targeted at recurrent depressive disorder.

TRIAL REGISTRATION: ClinicalTrials.gov: NCT04211961. Registered 26th December 2019. https://clinicaltrials.gov/study/NCT04211961?term=NCT04211961&rank=1 EudraCT Number: 2017-003112-39.