Effects of Short-Term Varenicline Administration on Emotional and Cognitive Processing in Healthy, Non-Smoking Adults: A Randomized, Double-Blind, Study

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.

Varenicline effects on drinking, craving and neural reward processing among non-treatment-seeking alcohol-dependent individuals

“…Although this effect was relatively small, and its clinical relevance is unknown, it is possible that, had the study lasted longer or the subjects been motivated to cut down or stop drinking, this increase in control might have led to reduced drinking over time. Preclinical and clinical data indicate that varenicline blocks cue-induced reinstatement of alcohol consumption among rats that have acquired alcohol self-administration (Wouda, et al, 2011), and may enhance cognition among both healthy controls (Mocking et al, 2013) and abstinent smokers (Loughead et al, 2010). Given that subjects continued to drink heavily during the treatment period, other potential mechanisms for varenicline’s effects on drinking, including potentiation of the sedative (Kamens, et al, 2010a) and negative subjective effects of alcohol (Childs, et al, 2012), may also have contributed to an increase in perceived behavioral control.…”

Cognitive control in alcohol use disorder: deficits and clinical relevance

“…Nicotinic agonists (nicotine, varenicline) have been shown to improve attention and working memory in non-smokers (Ceballos et al, 2005; Brady et al, 2011; Mocking et al, 2013). Moreover, in heavy drinking smokers, varenicline may decrease craving and drinking (McKee et al, 2009).…”

Effect of Varenicline Combined with High-Dose Alcohol on Craving, Subjective Intoxication, Perceptual Motor Response, and Executive Cognitive Function in Adults with Alcohol Use Disorders: Preliminary Findings

“…Varenicline has also been shown to speed reaction time on measures of attention in nicotine-deprived smokers (Ashare and McKee, 2012). Independent of smoking, healthy subjects also demonstrate enhanced effects on working and declarative memory following a short-term, low dose (up to 1 mg/day) varenicline regimen (Mocking et al, 2013). …”

“…We hypothesized that 1 and 2mg/day varenicline (versus placebo) would reduce craving and subjective intoxication following alcohol consumption (McKee et al, 2009). Based on work in smokers and non-smokers demonstrating that varenicline improves cognitive function (Patterson et al, 2009, Loughead et al, 2010, Mocking et al, 2013), we predicted that varenicline would improve cognitive function overall. It was unknown what effect varenicline would have on alcohol-related impairments in cognitive function and perceptual motor tasks.…”