Dose-dependent effects of Varenicline on tobacco craving and withdrawal in tobacco smokers with and without schizophrenia.

Abstract

People with schizophrenia (SCZ) have significantly higher tobacco smoking rates and lower quit rates than the general population. Varenicline, a partial agonist at α4β2 nicotinic acetylcholine receptors (nAChRs) is an effective smoking cessation pharmacotherapy, however, investigation into its effects in SCZ are less well-studied and mechanisms may differ from non-psychiatric controls due to dysregulation in nAChR neurotransmission associated with SCZ. Here, we investigate whether Varenicline attenuates acute abstinence-induced increases in craving and withdrawal in participants with and without SCZ. Following biochemically-verified overnight abstinence and subsequent smoking reinstatement, individuals with nicotine-dependence (n = 13 SCZ or schizoaffective; n = 12 controls) were assessed on the Minnesota Nicotine Withdrawal Scale (MNWS) and Tiffany Questionnaire for Smoking Urges (TQSU). Participants were pretreated in a double-blind, counterbalanced manner with Varenicline (0, 1 or 2 mg/day x 3 days) over three separate weeks. Data were analyzed using linear mixed-effects modelling and estimated marginal means. Robust effects of smoking abstinence were observed on TQSU and MNWS scores in SCZ and control participants. Relative to 1 mg, 2 mg/day of Varenicline attenuated abstinence-induced increases in craving (TQSU Factor 1 d=-0.47, p = .006; TQSU Factor 2 d=-0.42, p = .008) and withdrawal (MNWS d=-0.35, p = .03) in both groups. Our preliminary findings suggest that subacute Varenicline treatment reduces abstinence-induced craving and withdrawal in participants with and without SCZ. The efficacy of Varenicline on tobacco withdrawal and craving requires further study.