Varenicline Augmentation in Depressed Smokers: An 8-Week, Open-Label Study
Open accessAbstract
OBJECTIVE: To assess possible antidepressant effects of varenicline augmentation in outpatients with treatment-resistant depressive disorders and nicotine dependence. BACKGROUND: Varenicline is a nicotinic acetylcholine receptor alpha4beta2 partial agonist and alpha7 full agonist approved for smoking cessation. Studies of similar compounds have suggested evidence of antidepressant effects. METHOD: Eighteen patients (aged 18 to 65 years) were recruited from a general psychiatric outpatient clinic. Inclusion criteria were (1) primary Axis I depressive disorder (DSM-IV-TR criteria), (2) a stable antidepressant or mood stabilizer regimen, (3) persistent depressive symptoms despite adequate treatment, and (4) current cigarette smoking with nicotine dependence. Patients received varenicline (started at 0.5 mg daily and titrated to 1 mg twice daily) in addition to stable doses of their regular psychotropic medications. Depression symptoms, side effects, clinical global impressions, anhedonia, daily cigarette consumption, and vital signs were assessed every 2 weeks for 8 weeks. Baseline and endpoint ratings were compared, and the relationship between mood improvement and smoking cessation was examined. The primary outcome variable was mean change score in depressive symptoms as assessed by the 16-item Quick Inventory of Depressive Symptomatology-Self-Report. The study was conducted between September 2007 and March 2008. RESULTS: Fourteen patients (78%) completed the study; 4 discontinued due to side effects, including gastrointestinal effects (n = 3) and worsened mood/irritability (n = 1). Patients demonstrated significant improvement in depression at end point (p < .001), with significant improvement as early as week 2. Eight patients (44%) met criteria for categorical response, and 6 (33%) reached remission criteria; the overall effect size was large. All patients were interested in smoking cessation: 8 (44%) achieved abstinence and 9 (50%) had some reduction in smoking. Improvement in depressive symptoms was correlated with smoking cessation. There was no evidence of treatment-emergent suicidality. CONCLUSION: Open-label varenicline augmentation was associated with significant improvement in mood in a small sample of outpatient smokers with persistent depressive symptoms. Larger, double-blind studies are needed to investigate potential antidepressant effects of varenicline augmentation. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00525837.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Nicotinic partial agonists are effective in human smokers.
“and in human smokers (Philip et al. 2009)”
From Mechanisms of Nicotine Addiction (2021) · cites this paper as Philip et al. 2009
The Introduction identifies varenicline as a nicotinic partial agonist, and the Abstract Results report improved depressive symptoms and reduced smoking among depressed smokers who received it. But this eight-week, open-label study of one drug does not establish that nicotinic partial agonists as a class are effective in human smokers generally; the Discussion says the findings suggest varenicline may have antidepressant properties in smokers with treatment-resistant depression. No page numbers are available in our copy. (LLM, conf=0.84)
Experimental — accuracy not yet measuredVarenicline has been reported to boost antidepressant effects in smokers with depression.
“Clinically, varenicline has demonstrated enhancement of both positive affect and cognitive function during smoking cessation (Patterson et al., 2009), and it was recently shown to augment the effects of antidepressants in depressed smokers (Philip et al., 2009).”
From Nicotinic Partial Agonists Varenicline and Sazetidine-A Have Differential Effects on Affective Behavior (2010) · cites this paper as Philip et al., 2009
Coadministration of varenicline positively enhances the effects of antidepressants in depressed smokers in a small open-label study.
“In addition, coadministration of varenicline was shown to positively enhance the effects of antidepressants in depressed smokers in a small open label study (Philip et al., 2009).”
From Nicotinic Partial Agonists Varenicline and Sazetidine-A Have Differential Effects on Affective Behavior (2010) · cites this paper as Philip et al., 2009
Similar compounds have shown promising effects in smaller clinical trials, and enhanced the effects of SSRIs in human depressed subjects.
“similar compounds have shown promising effects in smaller clinical trials, and enhanced the effects of SSRIs in human depressed subjects (George et al., 2008; Philip et al., 2009)”
From Mood and anxiety regulation by nicotinic acetylcholine receptors: A potential pathway to modulate aggression and related behavioral states (2015) · cites this paper as Philip et al., 2009
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 32 · Cited by 86
Research works printed but not linked: 1
- [16]Breslau N Psychiatric comorbidity of smoking and nicotine dependence Behav Genet 1995 25 95 101 7733862
- Authors
- Philip, N. S., Carpenter, L. L., Tyrka, A. R., Whiteley, L. B., & Price, L. H.
- Affiliations
- Brown University (US)
- Corresponding author
- Price, Lawrence H.
- Venue
- The Journal of Clinical Psychiatry
- Publisher
- Physicians Postgraduate Press, Inc
- Published
- 2009-03-24
- Volume
- 70
- Issue
- 7
- Pages
- 1026-1031
- ISSN
- 0160-6689 (ISSN-L)
- PMC
- PMC4915480
- OpenAlex
- W1979261550
- Cited by
- 86
- References
- 32
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 1 · 2020: 5 · 2019: 2 · 2018: 2 · 2017: 3 · 2016: 7 · 2015: 11 · 2014: 6 · 2013: 6 · 2012: 12
- FWCI
- 8.86
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Clinical Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (T32MH067553)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Keywords
- varenicline, antidepressant augmentation, treatment-resistant depression, nicotine dependence, smoking cessation, nicotine receptor partial agonist, anhedonia, depressive symptoms, psychiatric outpatients
- MeSH terms
- Varenicline, Smoking Prevention, Adolescent, Adult, Aged, Benzazepines, Depressive Disorder, Double-Blind Method, Drug Administration Schedule, Female, Humans, Male, Middle Aged, Personality Inventory, Psychotropic Drugs, Quinoxalines, Receptors, Nicotinic, Severity of Illness Index, Tobacco Use Disorder, Smoking Cessation, Treatment Outcome, Diagnostic and Statistical Manual of Mental Disorders
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
