Scopolamine produces larger antidepressant and antianxiety effects in women than in men
Open accessAbstract
Some antidepressant agents generate differential benefit based on gender. Blocking cholinergic muscarinic receptors using scopolamine produces robust and rapid antidepressant effects in males and females combined. This study evaluated if males and females differ in the antidepressant response magnitude following scopolamine administration. A total of 52 male and female outpatients meeting criteria for recurrent major depressive or bipolar disorder participated in a double-blind, randomized, placebo-controlled, crossover clinical trial involving seven i.v. infusions of placebo or scopolamine (4 μg/kg). Following a single-blind placebo lead-in, participants entered either a placebo-block/scopolamine-block or a scopolamine-block/placebo-block sequence. Each block included three sessions. Clinical ratings were acquired before each infusion and included the Montgomery-Asberg Depression Rating Scale (MADRS) and the Hamilton Anxiety Rating Scale (HAM-A). A treatment group × block interaction (F=21.0, p<0.001) was observed in MADRS scores across gender, and the reduction was significant by the evaluation following the first scopolamine administration (F=8.4, p=0.006). The treatment group × block interaction was also significant in males (F=3.8, p=0.043) and females (F=35.6, p<0.001) separately. A block × gender interaction (F=7.4, p=0.009) indicated that the response magnitude was larger in women. The treatment × block interaction was significant for the HAM-A across gender (F=12.0, p<0.001), and was significant for females (F=24.9, p<0.001) but not for males (F=1.3, p=0.30). When comparing the baseline block to study end, the block × gender interaction (F=12.6, p=0.001) showed that the antianxiety response was greater in women. Men and women show a rapid antidepressant response following scopolamine, but the magnitude of response is larger in women than in men.
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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 et al., 2010
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Acetylcholine as a Neuromodulator: Cholinergic Signaling Shapes Nervous System Function and Behavior
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- Authors
- Furey, M. L., Khanna, A., Hoffman, E. M., & Drevets, W. C.
- Affiliations
- National Institutes of Health (US)
- American University of the Caribbean School of Medicine (SX)
- Laureate Institute for Brain Research (US)
- Corresponding author
- Furey, Maura L
- Venue
- Neuropsychopharmacology
- Published
- 2010-08-25
- Volume
- 35
- Issue
- 12
- Pages
- 2479-2488
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC3055321
- OpenAlex
- W2057873186
- Cited by
- 138
- References
- 54
- Citations by year
- 2026: 1 · 2025: 9 · 2024: 26 · 2023: 3 · 2022: 11 · 2021: 5 · 2020: 12 · 2019: 9 · 2018: 9 · 2017: 5 · 2016: 7 · 2015: 8 · 2014: 7 · 2013: 8 · 2012: 10
- FWCI
- 5.87
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- scopolamine, muscarinic receptor antagonism, antidepressant effects, anxiolytic effects, sex differences, major depressive disorder, bipolar disorder, rapid antidepressant response, cholinergic blockade
- MeSH terms
- Adolescent, Adult, Antidepressive Agents, Bipolar Disorder, Major Depressive Disorder, Double-Blind Method, Female, Humans, Male, Middle Aged, Placebos, Psychiatric Status Rating Scales, Scopolamine, Sex Characteristics, Anti-Anxiety Agents, Single-Blind Method
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