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.

Figure 1

Participant flow. Participant flow chart and drop-out (based on a template from Consort 2010).

Figure 2

Mean z-scores of startle reactivity for pleasant, unpleasant, and neutral stimuli among non-smoking healthy subjects after 7 day randomized treatment with placebo (N=20) or varenicline (N=18). Error bars represent SEM.

Figure 3

Mean percentage of correctly remembered letters (‘hits') in four parts of the n-back task with increasing difficulty among non-smoking healthy subjects after 7 day randomized treatment with placebo (N=20) or varenicline (N=18). Error bars represent SEM.

Figure 4

Recalled words as percentages of learning scores in the Rey auditory verbal learning test (RAVLT) among non-smoking subjects after 7 day randomized treatment with placebo (N=20) or varenicline (N=18). Error bars represent SEM.