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Monoamine hypotheses hold that antidepressants act by enhancing noradrenergic, serotonergic, and/or dopaminergic neurotransmission. To explore an alternative concept, researchers conducted a double-blind, placebo-controlled, randomized, crossover study of scopolamine, a muscarinic cholinergic antagonist medication without effects on these monoamines, in 22 patients with moderate-to-severe major depression.
After a single-blind, placebo run-in, patients received three 15-minute intravenous infusions of scopolamine (4 µg/kg) or placebo 3 to 5 days apart and were then crossed over to the other study arm. Within each crossover group, depression ratings decreased significantly more with scopolamine than with placebo. During the first three treatm…