Abstract
Varenicline is an effective and increasingly prescribed drug for smoking cessation, but has been associated with depressive symptoms and suicidal behavior. However, it remains unclear whether those changes in mood and behavior are directly related to varenicline use, or caused by smoking cessation itself or reflects depression and suicidality rates in smokers, independent of treatment. To investigate the influence of varenicline on mood and behavior independent of smoking and smoking cessation, we assessed the effects of varenicline on emotional processing (a biomarker of depressogenic effects), emotion-potentiated startle reactivity, impulsivity (linked with suicidal behavior), and cognitive performance in non-smoking subjects. We used a randomized, double-blind design, in which we administered varenicline or placebo to healthy subjects over 7 days (0.5 mg/day first 3 days, then 1 mg/day). Cognitive and emotional processing was assessed by a battery of computerized tasks and recording of emotion-potentiated startle response. A total of 41 subjects were randomized, with 38 subjects included in the analysis. The varenicline group did not differ from placebo in terms of negative biases in emotional processing or mood. However, compared with placebo, the varenicline group scored higher on working and declarative memory. In conclusion, short-term varenicline use did not influence negative biases in emotional processing or impulsivity in non-smoking subjects, thereby not supporting direct depressogenic or suicidal risk behavior-inducing effects. In contrast, varenicline may have cognitive-enhancing effects.
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Acknowledgements
We are most grateful to the participants of our study. Funding support for this study was provided by the Medical Research Council G0801432/1. Study’s funding sources had no role in the study design; collection, analysis, and interpretation of data; writing of the report; and decision to submit the paper for publication. The corresponding author had full access to all the data and had final responsibility for the decision to submit for publication.
Author Contributions
AP, PJC, and CJH designed the study. RJTM, CPP, AP, EP, and SFM collected the data. RJTM, CPP, AP, and EP analyzed the data. RJTM and CPP drafted the manuscript. All authors participated in interpretation of the final results and editing of the report. All authors saw and approved the final version of the report.
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CJH serves on the advisory board of P1vital, and receives consultancy fees from and has shares in the company; and is also a director of Oxford Psychologists. PJC has been a paid member of advisory boards of Eli Lilly, Lundbeck and Servier, and has received remuneration for scientific advice given to legal representatives of GlaxoSmithKline. The remaining authors declare no conflict of interest.
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Mocking, R., Patrick Pflanz, C., Pringle, A. et al. Effects of Short-Term Varenicline Administration on Emotional and Cognitive Processing in Healthy, Non-Smoking Adults: A Randomized, Double-Blind, Study. Neuropsychopharmacol 38, 476–484 (2013). https://doi.org/10.1038/npp.2012.205
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DOI: https://doi.org/10.1038/npp.2012.205
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