Replication of Scopolamine's Antidepressant Efficacy in Major Depressive Disorder: A Randomized, Placebo-Controlled Clinical Trial

  • Wayne C. Drevets
    Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland
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  • Maura L. Furey
    Address correspondence to Maura L. Furey, Ph.D., Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, Building 15K, Room 201, Bethesda, MD 20892
    Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland
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      We previously reported that intravenous (IV) scopolamine administration produced rapid and robust antidepressant effects in a sample consisting of both unipolar and bipolar depressives. The present study aimed to replicate this finding in an independent sample limited to unipolar depressives.


      Outpatients with major depressive disorder (MDD; n = 23; 22 were included in analyses) participated in a double-blind, placebo-controlled, crossover trial. Subjects were randomized into either a P/S or S/P sequence (P = block of three placebo sessions; S = block of three scopolamine sessions; [4.0 μg/kg IV]). Sessions occurred 3 to 5 days apart, such that time spent in each block lasted 1.5 to 2 weeks and the interval between blocks was 3 to 5 days. The Montgomery-Asberg Depression Rating Scale (MADRS) served as the primary outcome measure.


      Following the initial block, the group receiving scopolamine first (S/P) showed a 32% reduction in MADRS scores (p < .001), which exceeded the corresponding change of 6.5% under placebo (P/S; p = .009), confirming the a-priori hypothesis. Improvement was significant at the first evaluation that followed scopolamine administration (p = .011). In Block 2, the P/S group showed a 53% reduction in MADRS scores (p = .001) following scopolamine versus placebo, whereas the reduction seen in S/P subjects who received scopolamine during Block 1 persisted as they received placebo during Block 2. Scopolamine induced drowsiness, blurred vision, dry mouth, light-headedness, and reduced blood pressure, which were sufficiently well tolerated that no subject dropped out because of side effects.


      These results replicate previous finding that scopolamine produces a rapid and robust antidepressant response.

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