Effects of the Nicotinic Partial Agonist Varenicline on Smoking Lapse Behaviour in Schizophrenia

Abstract

Résumé Background: Varenicline, a nicotinic receptor partial agonist, is a first-line smoking cessation pharmacotherapy that may reduce smoking relapse in smokers with schizophrenia (SWS). The use of human laboratory models may allow the determination of potential mechanisms to improve treatment outcomes. The first instance of smoking during a quit attempt (a “smoking lapse”) is one of the best predictors of relapse. The aim of this study was to investigate effects of varenicline on smoking lapse in SWS and controls using a validated model of smoking lapse behaviours. Methods: Varenicline was titrated up to 2 mg/d over 4 days and continued for a total of 6 days using a randomized, double-blind, placebo-controlled cross-over human laboratory lapse study design in SWS (n = 14) and nonpsychiatric control (n = 14) smokers. Results: Varenicline nonsignificantly increased time to lapse in both SWS and control groups. However, these effects were most pronounced in SWS compared to controls with higher levels of nicotine dependence (Fagerström Test for Nicotine Dependence score ≥6; Cohen's d = 0.47 SWS; d = 0.24 controls). There were no medication effects related to cognitive function, withdrawal, craving, or smoking topography outcomes. Conclusions: Our preliminary findings lack evidence in supporting the potential efficacy of varenicline on smoking relapse, particularly in SWS that may in part relate to our small sample size. Larger studies to further delineate the specific mechanisms by which varenicline ameliorates smoking relapse in SWS are needed, possibly in combination with adjunctive treatments to enhance overall relapse-prevention outcomes. Contexte: La varénicline, sevrage partiel des récepteurs nicotiniques, est une pharmacothérapie de premier plan susceptible de réduire les rechutes du tabagisme chez les fumeurs atteints de schizophrénie (SWS). L’utilisation de modèles humains en laboratoire peut permettre de déterminer les mécanismes potentiels pour améliorer les résultats du traitement. La première occurrence de tabagisme au cours d’une tentative d’arrêt du tabac (un «manque de nicotine») est l’un des meilleurs annonciateurs de rechute. Le but de cette étude était d’étudier les effets de la varénicline sur les rechutes de tabagisme chez les patients SWS et les contrôles à l’aide d’un modèle validé de comportements lors de rechute de tabagisme. Méthodes: La varénicline a été administrée jusqu’à 2 mg / jour sur 4 jours et poursuivie pendant 6 jours lors d’une étude aléatoire, ainsi qu’à double insu de contrôle placebo, en laboratoire, chez des patients atteints de schizophrénie (n = 14), ainsi que chez des sujets sous aucun contrôle psychiatrique (n = 14) fumeurs. Résultats: La varénicline a démontré un effet non-significatif dans le temps de rechute chez les sujets des deux groupes. Toutefois les effets étaient plus prononcés chez les enfants SWS que chez les témoins présentant des niveaux plus élevés de dépendance à la nicotine (score FTND > 6; d Cohen = d 0,47, schizophrénie; d = 0,24). Aucun effet médicamenteux lié aux fonctions cognitives, au sevrage, à l’état de manque ou à la topographie du tabagisme n’a été observé. Conclusions: Les résultats préliminaires n’ont démontré aucune efficacité significative de la varénicline dans la suppression des rechutes au tabagisme, surtout chez les sujets souffrants de schizophrénie. Cependant, ces résultats peuvent dépendre en partie du faible nombre de sujets. Des études plus vastes visant à définir plus précisément les mécanismes spécifiques par lesquels la varénicline améliore la rechute du tabagisme dans la schizophrénie sont nécessaires, éventuellement en association avec des traitements d’appoint pour améliorer les résultats globaux en matière de prévention des rechutes.

Effects of varenicline and bupropion on laboratory smoking outcomes: Meta‐analysis of randomized, placebo‐controlled human laboratory studies

“…Ad libitum smoking comprised mean cigarettes smoked during laboratory smoking breaks 36 and 1‐, 20,30 3‐ 37 or 4‐h 38 self‐administration phases. Time to lapse data comprised one varenicline study using McKee and colleagues' smoking lapse paradigm 20 comprising post‐treatment mean time to lapse after overnight abstinence 28 . Smoking topography data comprised average change in full cigarette puff count, time smoking and latency to begin smoking (reverse coded) 6 and average change in puff count, puff volume and puff duration 25 from pretreatment to end of pharmacotherapy.…”

“…Means and standard errors were measured and extracted from graphs when necessary for effect size calculation. Effect sizes of the same outcome derived from multiple participant subgroups or similar measures/indices within a single study were averaged such that each study contributed only one effect size to each meta‐analysis, including averaging across sex, 18 multiple factors of craving or withdrawal, 6,19–22 smoking topography measures, 6,23–25 craving instruction sets 26 and subgroups of participants defined based on intention to quit smoking 23,27 or psychiatric diagnosis 28 …”

“…Time to lapse data comprised one varenicline study using McKee and colleagues' smoking lapse paradigm 20 comprising post-treatment mean time to lapse after overnight abstinence. 28 Smoking topography data comprised average change in full cigarette puff count, time smoking and latency to begin smoking (reverse coded) 6 and average change in puff count, puff volume and puff duration 25 from pretreatment to end of pharmacotherapy. Smoking topography data also represented posttreatment average puff count, puff volume and carbon monoxide (CO) boost 23 and average puff count, puff volume, puff duration, puff velocity and inter-puff interval (reverse coded).…”

“…20,34 effect size to each meta-analysis, including averaging across sex, 18 multiple factors of craving or withdrawal, 6,[19][20][21][22] smoking topography measures, 6,[23][24][25] craving instruction sets 26 and subgroups of participants defined based on intention to quit smoking 23,27 or psychiatric diagnosis. 28 Data also were extracted to explore potential moderators of effect size estimates. Sample characteristics extracted included proportion of men (coded to assume binary classifications if not specified and to include data reported as 'sex' if descriptions were inconclusive) and mean participant age.…”