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Clinical Trial
. 2024 Oct 1:362:416-424.
doi: 10.1016/j.jad.2024.07.025. Epub 2024 Jul 14.

Effects of open-label transdermal nicotine antidepressant augmentation on affective symptoms and executive function in late-life depression

Patricia Andrews  1 , Jennifer N Vega  1 , Sarah M Szymkowicz  1 , Paul Newhouse  2 , Rachel Tyndale  3 , Damian Elson  1 , Hakmook Kang  4 , Sarah Siddiqi  1 , Elizabeth B Tyner  1 , Kathleen Mather  1 , Faith M Gunning  5 , Warren D Taylor  6
Affiliations
Clinical Trial

Effects of open-label transdermal nicotine antidepressant augmentation on affective symptoms and executive function in late-life depression

Patricia Andrews et al. J Affect Disord. .

Abstract

Background: Late-life depression (LLD) is characterized by a poor response to antidepressant medications and diminished cognitive performance, particularly in executive functioning. There is currently no accepted pharmacotherapy for LLD that effectively treats both mood and cognitive symptoms. This study investigated whether transdermal nicotine augmentation of standard antidepressant medications benefitted mood and cognitive symptoms in LLD.

Methods: Nonsmoking participants aged 60 years or older with unremitted LLD on stable SSRI or SNRI medications (N = 29) received transdermal nicotine patches up to a 21 mg daily dose over 12 weeks. Clinical measures assessed depression severity, secondary affective symptoms, and cognitive performance. Nicotine metabolite concentrations were obtained from blood samples.

Results: Depression severity significantly decreased over the trial, with a 76 % response rate and 59 % remission rate. Change in depression severity was positively associated with nicotine exposure. Participants also exhibited improvement in self-reported affective symptoms (apathy, insomnia, rumination, and generalized anxiety symptoms), negativity bias, and disability. Executive function test performance significantly improved, specifically in measures of cognitive control, as did subjective cognitive performance. Adverse events were generally mild, with 75 % of the sample tolerating the maximum dose.

Conclusion: The current study extends our previous pilot open-label trial in LLD, supporting feasibility and tolerability of transdermal nicotine patches as antidepressant augmentation. Although preliminary, this open-label study supports the potential benefit of transdermal nicotine patches for both mood and cognitive symptoms of LLD. Further research, including definitive randomized, blinded trials, is warranted to confirm these findings and explore long-term risk and benefit.

Trial registration: The study was registered with clinicaltrials.gov (NCT04433767).

Keywords: Acetylcholine; Clinical trial; Depression; Executive function; Geriatrics; Nicotine.

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Conflict of interest statement

Declaration of competing interest The authors report no conflicts of interests, including no conflicts with any product mentioned or concept discussed in this article.

Figures

Figure 1.
Figure 1.
CONSORT Diagram One participant withdrew after completing week 6 assessments due to adverse events. All other participants completed the 12-week trial.
Figure 2.
Figure 2.
Change in depression severity and nicotine metabolite levels Figure 2.A displays change in depression severity by MADRS (Montgomery Asberg Depression Rating Scale) score over time. Figures 2.B and 2.C display change in nicotine concentrations (ng/ml) and cotinine + 3-hydroxycotinine concentrations (COT+3HC; ng/ml) over time, excluding outlier values. Mean values displayed with a horizontal bar, while the box displays the interquartile range. Error bars display the upper and lower values of data within the outlier range, defined as 1.5x the interquartile range.
See this image and copyright information in PMC

Comment in

  • Transdermales Nikotin bei Depression?
    Hüll M. Hüll M. MMW Fortschr Med. 2025 Mar;167(4):28. doi: 10.1007/s15006-025-4764-3. MMW Fortschr Med. 2025. PMID: 40050585 Review. German. No abstract available.

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