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.
Patterson
Freda
F
Department of Psychiatry, University of Pennsylvania, University of Pittsburgh Medical Center, 3811 O'Hara St., Pittsburgh, PA 15213, USA.
Jepson
Christopher
C
Strasser
Andrew A
AA
Loughead
James
J
Perkins
Kenneth A
KA
Gur
Ruben C
RC
Frey
Joseph M
JM
Siegel
Steven
S
Lerman
Caryn
C
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