Cited by 130Treatment of Major DepressionNicotinic Acetylcholine Receptors StudySmoking Behavior and Cessation

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Nicotinic Antagonist Augmentation of Selective Serotonin Reuptake Inhibitor-Refractory Major Depressive Disorder: A Preliminary Study

George, Tony P., Sacco, Kristi A., Vessicchio, Jennifer C., Weinberger, Andrea H., Shytle, R. Douglas·2008·Journal of Clinical Psychopharmacology

DOI 10.1097/jcp.0b013e318172b49e

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Abstract

BACKGROUND: There is evidence for nicotinic hypercholinergic mechanisms in depression. Clinical relationships between tobacco use and depression suggest important effects of nicotine in major depressive disorder (MDD). It has been hypothesized that cigarette smoking may exert antidepressant effects, presumably mediated through stimulation of nicotinic acetylcholine receptor systems. We compared the nicotinic antagonist, mecamylamine hydrochloride (MEC), with placebo as an augmentation strategy for patients with MDD who were refractory to selective serotonin reuptake inhibitor (SSRI) treatment. METHODS: Twenty-one SSRI-treated subjects with MDD were randomized to MEC (up to 10 mg/d; n = 11) or placebo (PLO group; n = 10) during an 8-week trial. The primary outcome measure was the change in depressive symptoms assessed using the 17-item Hamilton Depression Rating Scale during the 8-week trial. RESULTS: There was a significant reduction in 17-item Hamilton Depression Rating Scale scores in the MEC versus PLO groups, as evidenced by a significant medication x time interaction (F1,19 = 6.47, P < 0.05). Five (45.5%) of 11 subjects in the active study medication group demonstrated a 50% or more decrease in depressive symptoms from baseline as compared with 1 (10%) of 10 subjects assigned to placebo medication, but this difference was not significant (P = 0.15; Fisher exact test). The primary side effects of MEC were constipation and orthostatic hypotension. CONCLUSIONS: These preliminary findings suggest that the nicotinic acetylcholine receptor antagonist, MEC, may have utility as an augmentation strategy for patients with SSRI-refractory MDD.

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Authors: George, T. P., Sacco, K. A., Vessicchio, J. C., Weinberger, A. H., & Shytle, R. D.
Affiliations: Centre for Addiction and Mental Health (CA)
Yale University (US)
University of South Florida (US)
Corresponding author: George, Tony P.
Sacco, Kristi A.
Vessicchio, Jennifer C.
Weinberger, Andrea H.
ORCID: George, Tony P.
Weinberger, Andrea H.
Shytle, R. Douglas
Venue: Journal of Clinical Psychopharmacology
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2008-06
Volume: 28
Issue: 3
Pages: 340-344
ISSN: 0271-0749 (ISSN-L)
DOI: 10.1097/jcp.0b013e318172b49e
OpenAlex: W1985905713
Cited by: 128
References: 17
Citations by year: 2026: 2 · 2024: 3 · 2023: 4 · 2022: 2 · 2021: 3 · 2020: 6 · 2019: 3 · 2018: 4 · 2017: 6 · 2016: 6 · 2015: 8 · 2014: 10 · 2013: 11 · 2012: 13
FWCI: 10.78
Type: journal article
Language: en
Open access: closed
Locations: Journal of Clinical Psychopharmacology (publishedVersion)
PubMed (publishedVersion)
Funders: Eli Lilly and Company
Pfizer
University of South Florida
Ministerio de Economía y Competitividad
National Institute on Drug Abuse (5K02 DA 16611, K02DA016611)
Topics: Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Smoking Behavior and Cessation
Keywords: major depressive disorder, mecamylamine, nicotinic acetylcholine receptor antagonism, antidepressant augmentation, nicotine, depressive symptoms
MeSH terms: Adult, Depressive Disorder, Major, Major Depressive Disorder, Drug Resistance, Drug Therapy, Combination, Female, Follow-Up Studies, Humans, Male, Mecamylamine, Middle Aged, Personality Inventory, Psychometrics, Selective Serotonin Reuptake Inhibitors, Nicotinic Antagonists

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Nicotinic Antagonist Augmentation of Selective Serotonin Reuptake Inhibitor-Refractory Major Depressive Disorder: A Preliminary Study

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