Varenicline improves mood and cognition during smoking abstinence.
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.
Department of Psychiatry, University of Pennsylvania, University of Pittsburgh Medical Center, 3811 O'Hara St., Pittsburgh, PA 15213, USA.
Freda
F
Patterson
Christopher
C
Jepson
Andrew A
AA
Strasser
James
J
Loughead
Kenneth A
KA
Perkins
Ruben C
RC
Gur
Joseph M
JM
Frey
Steven
S
Siegel
Caryn
C
Lerman
D000328:Adult; D000339:Affect / Q000187:drug effects*; D001288:Attention / Q000187:drug effects; D001552:Benzazepines / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects; D008875:Middle Aged; D018722:Nicotinic Agonists / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology*; D011930:Reaction Time / Q000187:drug effects; D016540:Smoking Cessation; D013375:Substance Withdrawal Syndrome / Q000517:prevention & control*; D000068580:Varenicline
D001552:Benzazepines; D018722:Nicotinic Agonists; D011810:Quinoxalines; D000068580:Varenicline