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Cited by 417Treatment of Major DepressionNeurotransmitter Receptor Influence on BehaviorTryptophan and brain disorders

Antidepressant Efficacy of the Antimuscarinic Drug Scopolamine: A Randomized, Placebo-Controlled Clinical Trial

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Furey, Maura L., Drevets, Wayne C.·2006·Archives of General Psychiatry
DOI 10.1001/archpsyc.63.10.1121PMC PMC3250308
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Abstract

CONTEXT: The need for improved therapeutic agents that more quickly and effectively treat depression is critical. In a pilot study we evaluated the role of the cholinergic system in cognitive symptoms of depression and unexpectedly observed rapid reductions in depression severity following the administration of the antimuscarinic drug scopolamine hydrobromide (4 microg/kg intravenously) compared with placebo (P = .002). Subsequently a clinical trial was designed to assess more specifically the antidepressant efficacy of scopolamine. OBJECTIVE: To evaluate scopolamine as a potential antidepressant agent. DESIGN: Two studies were conducted: a double-blind, placebo-controlled, dose-finding study followed by a double-blind, placebo-controlled, crossover clinical trial. SETTING: The National Institute of Mental Health. Patients Currently depressed outpatients aged 18 to 50 years meeting DSM-IV criteria for recurrent major depressive disorder or bipolar disorder. Of 39 eligible patients, 19 were randomized and 18 completed the trial. INTERVENTIONS: Multiple sessions including intravenous infusions of placebo or scopolamine hydrobromide (4 microg/kg). Individuals were randomized to a placebo/scopolamine or scopolamine/placebo sequence (series of 3 placebo sessions and series of 3 scopolamine sessions). Sessions occurred 3 to 5 days apart. MAIN OUTCOME MEASURES: Psychiatric evaluations using the Montgomery-Asberg Depression Rating Scale and the Hamilton Anxiety Rating Scale were performed to assess antidepressant and antianxiety responses to scopolamine. RESULTS: The placebo/scopolamine group showed no significant change during placebo infusion vs baseline; reductions in depression and anxiety rating scale scores (P<.001 for both) were observed after the administration of scopolamine compared with placebo. The scopolamine/placebo group also showed reductions in depression and anxiety rating scale scores (P<.001 for both) after the administration of scopolamine, relative to baseline, and these effects persisted as they received placebo. In both groups, improvement was significant at the first evaluation after scopolamine administration (P< or =.002). CONCLUSION: Rapid, robust antidepressant responses to the antimuscarinic scopolamine occurred in currently depressed patients who predominantly had poor prognoses.

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  • Clinical trials have suggested that blockade of either mAChRs or nAChRs can decrease symptoms of depression.

    “clinical trials have suggested that blockade of either mAChRs (Furey and Drevets, 2006; Furey et al., 2010) or nAChRs (George et al., 2008; Shytle et al., 2002) can decrease symptoms of depression.”

    From Acetylcholine as a Neuromodulator: Cholinergic Signaling Shapes Nervous System Function and Behavior (2012) · cites this paper as Furey and Drevets, 2006

  • Results obtained from a small proof-of-concept study failed to provide a sign of efficacy of scopolamine in the cognitive domain of selective attention.

    “Notwithstanding a preclinical and pharmacological rationale for scopolamine possibly offering procognitive benefits for MDD, results obtained from a small proof-of-concept study failed to provide a sign of efficacy in the cognitive domain (selective attention) [154].”

    From Cognitive remission: a novel objective for the treatment of major depression? (2016) · cites this paper as [154]

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Research works printed but not linked: 8

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Authors
Furey, M. L., & Drevets, W. C.
Affiliations
National Institutes of Health (US)
ORCID
Drevets, Wayne C.
Venue
Archives of General Psychiatry
Publisher
American Medical Association (AMA)
Published
2006-10-01
Volume
63
Issue
10
Pages
1121
ISSN
0003-990X (ISSN-L)
DOI
10.1001/archpsyc.63.10.1121
PMC
PMC3250308
OpenAlex
W2131722356
Cited by
417
References
63
Citations by year
2026: 11 · 2025: 13 · 2024: 15 · 2023: 20 · 2022: 17 · 2021: 22 · 2020: 28 · 2019: 23 · 2018: 23 · 2017: 25 · 2016: 27 · 2015: 30 · 2014: 24 · 2013: 43 · 2012: 20
FWCI
7.52
Type
journal article
Language
en
Open access
Locations
  • Archives of General Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Institute of Mental Health (ZIAMH002813)
Topics
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords
scopolamine, antidepressant efficacy, antimuscarinic agents, depression, major depressive disorder, bipolar disorder, cholinergic system, cognitive symptoms of depression, anxiety, intravenous administration, rapid antidepressant response
MeSH terms
Adult, Antidepressive Agents, Bipolar Disorder, Major Depressive Disorder, Depressive Disorder, Major, Depressive Disorder, Double-Blind Method, Female, Humans, Infusions, Intravenous, Male, Pilot Projects, Placebos, Psychiatric Status Rating Scales, Research Design, Scopolamine, Severity of Illness Index, Treatment Outcome, Muscarinic Antagonists

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