Scopolamine as an antidepressant: a systematic review.

OBJECTIVES: The cholinergic-adrenergic hypothesis of mania and depression states that depression is characterized by an increase in central cholinergic activity relative to noradrenergic tone. Scopolamine is a centrally acting competitive inhibitor of the muscarinic cholinergic receptor site. This review seeks to find all available data investigating scopolamine as an antidepressant. METHODS: A systematic review of all the published and unpublished or ongoing literature was conducted via Ovid MEDLINE. Keywords used for the search were "scopolamine hydrobromide" in association with one of the following: "depression," "antidepressive agents," "depressive disorder," "depression, chemical," and "affect." PubMed was also searched using "scopolamine" (all fields) and "antidepressant" (all fields) or "depression" (all fields). RESULTS: A small study with elderly patients failed to show a statistically significant improvement in depression when measured at 120 minutes after infusion. A second small, well-controlled study using intramuscular scopolamine showed a small but statistically significant improvement in depression on the morning after the second dose was received. Two double-blind randomized placebo-controlled crossover trials with intravenous scopolamine 4.0 μg/kg infusions showed a significant improvement in depressive symptoms seen as soon as 3 days after the first treatment. Further data analyses showed a greater antidepressant effect in women, significant improvements in bipolar depression, and 85% success rates predicting who will respond to treatment. CONCLUSIONS: Scopolamine is an effective and rapid antidepressant in both unipolar and bipolar depression, working as quickly as 3 days after initial infusion. Independent replication would greatly enhance the literature.