Varenicline improves mood and cognition during smoking abstinence

Abstract

Background: Neuronal nicotinic acetylcholine receptors (nAChRs) are a key target in medication development for various neuropsychiatric disorders, including nicotine dependence. Varenicline, a partial agonist at the alpha4beta2 nAChRs, is a new, efficacious medication for nicotine dependence. Its effects on the affective and cognitive dimensions of nicotine withdrawal have yet to be well characterized.

Methods: Sixty-seven treatment-seeking smokers were administered varenicline (x 21 days) and placebo (x 21 days) in a double-blind within-subject crossover design. Following medication run-up (Days 1-10), there was a 3-day mandatory smoking abstinence phase (Days 11-13) during which subjective symptoms and cognitive performance were assessed. Participants were reexposed to a scheduled smoking lapse (Day 14) and followed for days to lapse (Days 15-21) in each medication period.

Results: In the varenicline period, compared with placebo, withdrawal symptoms (p = .04), smoking urges (p < .001), and negative affect (p = .01) during manditory abstinence were significantly lower, and levels of positive affect (p = .046), sustained attention (p = .018), and working memory (p = .001) were significantly greater. Varenicline also significantly reduced subjective rewarding effects of the scheduled smoking lapse (e.g., satisfaction, relief, liking; p = .003). Medication effects on days to lapse following the scheduled smoking lapse were dependent on treatment order (p = .001); among participants who received placebo in the first period, varenicline increased days of abstinence in the follow-up period.

Conclusions: These data identify novel affective and cognitive effects of varenicline and may have implications for medication development for other neuropsychiatric conditions.

Conflict of interest statement

Financial Disclosures

Dr. Lerman has served as a paid consultant and has received funding from pharmaceutical companies which manufacture smoking cessation medications, including Pfizer (maker of Chantix®, varenicline) and GlaxoSmithKline. Dr. Frey is employed by Astra Zeneca. Dr. Siegel is a consultant to NuPathe and has received research support from AstraZeneca. Dr. Patterson, Dr. Jepson, Dr. Strasser, Dr. Loughead, Dr. Gur, and Dr. Perkins report no biomedical financial interests or potential conflicts of interest.

Figures

Figure 1

Study Schema.

Figure 2

Varenicline Effects on Lapse Cigarette Ratings.

Figure 3

CO-Verified Days to Lapse by Medication Phase and Treatment Order.