Varenicline

Abstract

Varenicline (Chantix, Champix) is an orally administered alpha4beta2 nicotinic acetylcholine receptor partial agonist that is indicated as an aid to smoking cessation. Well designed clinical trials indicate that varenicline is an effective aid to smoking cessation. During the last 4 weeks of treatment, carbon monoxide-confirmed continuous abstinence rates were generally significantly higher with varenicline than with placebo, bupropion sustained release (SR) or nicotine replacement therapy. Varenicline also reduced cravings, the reinforcing effects of smoking and some withdrawal symptoms. Another well designed trial demonstrated that extending varenicline therapy by an additional 12 weeks helped maintain abstinence in individuals who had quit smoking. Varenicline was generally well tolerated in clinical trials; nausea, the most commonly occurring adverse event, diminished over time. More data are needed regarding the potential for neuropsychiatric events in varenicline recipients. Some of these events may be associated with nicotine withdrawal, rather than varenicline, although neuropsychiatric events have been observed in individuals who continued to smoke whilst receiving varenicline. In modelled cost-effectiveness analyses based on data from clinical trials in participants receiving smoking cessation therapy, 12 weeks' treatment with varenicline was predicted to be cost effective from a healthcare payer perspective in numerous countries. With regard to the incremental costs per QALY or life-year gained, 12 weeks' treatment with varenicline consistently dominated bupropion SR and nicotine replacement therapy and was dominant over or considered cost effective relative to unaided cessation, regular brief counselling or nortriptyline in analyses based on Markov models. In additional modelled analyses from a healthcare payer perspective, administering varenicline for an additional 12 weeks in participants who had successfully quit smoking was estimated to have acceptable incremental costs per QALY gained relative to varenicline for 12 weeks and to dominate other smoking cessation options. Moreover, in Swedish analyses that also included societal costs for production and consumption, the incremental cost per QALY gained for varenicline versus bupropion SR, and for an additional 12 weeks of varenicline therapy versus varenicline for 12 weeks only, was below commonly accepted thresholds of cost effectiveness. A US decision-analytic model from the perspective of various US health insurance plans demonstrated that, after 2 years, varenicline was predicted to dominate bupropion SR, in terms of the incremental cost per additional smoking cessation. Varenicline was also dominant or cost effective versus nicotine replacement therapy, and cost effective versus unaided cessation. Sensitivity analyses demonstrated that the results of cost-effectiveness studies were generally robust to plausible variations in key parameters. In conclusion, varenicline is an effective aid to smoking cessation. Varenicline was generally well tole...

Substance Abuse Among Older Adults

“…132,133 It has also recently been applied to alcohol dependence in a similar fashion as naltrexone. 134 Although there are relatively few studies on varenicline with alcohol, existing studies demonstrate a reduction in drinking overall 135 or a reduction in heavy drinking 134 among a general population.…”

Effects of the combination of metyrapone and oxazepam on intravenous nicotine self-administration in rats

“…The 25:5 mg/kg combination of metyrapone and oxazepam also reduced nicotine self-administration maintained under a PR schedule of reinforcement, suggesting that the combination of metyrapone and oxazepam reduces the motivation to seek and take nicotine. Finally, the effects of the combination of metyrapone and oxazepam were comparable to those of the α4β2 nicotinic acetylcholine receptor partial agonist varenicline in this specific model of intravenous nicotine self-administration (George et al 2011; Keating and Lyseng-Williamson 2010; O’Connor et al 2010). Since varenicline is effective in reducing cigarette smoking in humans (Keating and Lyseng-Williamson 2010) and appears to be more beneficial than either bupropion (Cahill et al 2009; Gonzales et al 2006; Jorenby et al 2006) or nicotine replacement therapy (Aubin et al 2008; Cahill et al 2009), these data suggest that the combination of metyrapone and oxazepam may also be effective in reducing smoking (O’Dell and Khroyan 2009).…”

“…The chances of quitting increase significantly when individuals employ pharmacological approaches such as nicotine replacement therapy (Moore et al 2009; Ray et al 2007) and the antidepressant bupropion (Paterson 2009; Wilkes 2008). More recently, the α4β2 nicotinic acetylcholine receptor partial agonist varenicline (Keating and Lyseng-Williamson 2010) has been reported to increase efficacy for smoking cessation compared to either bupropion (Cahill et al 2009; Gonzales et al 2006; Jorenby et al 2006) or nicotine replacement therapy (Aubin et al 2008; Cahill et al 2009). However, there are reports of adverse events with varenicline (McNeil et al 2010) including suicidal ideation and behavior (Harrison-Woolrych 2009; Moore and Furberg 2009).…”

Smoking Cessation After Brain Damage Does Not Lead to Increased Depression

“…9, 11, 19, 48, 49 One large-scale study 50 analyzed medical records from more than 80,000 people who were trying to stop smoking—more than 10,000 of whom were using varenicline—and could not link varenicline to an increased risk of depression, suicidal thoughts, or fatal or non-fatal self-harm. Still, a 2-fold increased risk of self-harm with varenicline could not be ruled out on statistical grounds.…”