Nicotine receptor partial agonists for smoking cessation

Abstract

Background Nicotine receptor partial agonists may help people to stop smoking by a combination of maintaining moderate levels of dopamine to counteract withdrawal symptoms (acting as an agonist) and reducing smoking satisfaction (acting as an antagonist). This is an update of a Cochrane Review first published in 2007. Objectives To assess the effectiveness of nicotine receptor partial agonists, including varenicline and cytisine, for smoking cessation. Search methods We searched the Cochrane Tobacco Addiction Group's Specialised Register in April 2022 for trials, using relevant terms in the title or abstract, or as keywords. The register is compiled from searches of CENTRAL, MEDLINE, Embase, and PsycINFO. Selection criteria We included randomised controlled trials that compared the treatment drug with placebo, another smoking cessation drug, e‐cigarettes, or no medication. We excluded trials that did not report a minimum follow‐up period of six months from baseline. Data collection and analysis We followed standard Cochrane methods. Our main outcome was abstinence from smoking at longest follow‐up using the most rigorous definition of abstinence, preferring biochemically validated rates where reported. We pooled risk ratios (RRs), using the Mantel‐Haenszel fixed‐effect model. We also reported the number of people reporting serious adverse events (SAEs). Main results We included 75 trials of 45,049 people; 45 were new for this update. We rated 22 at low risk of bias, 18 at high risk, and 35 at unclear risk. We found moderate‐certainty evidence (limited by heterogeneity) that cytisine helps more people to quit smoking than placebo (RR 1.30, 95% confidence interval (CI) 1.15 to 1.47; I 2 = 83%; 4 studies, 4623 participants), and no evidence of a difference in the number reporting SAEs (RR 1.04, 95% CI 0.78 to 1.37; I 2 = 0%; 3 studies, 3781 participants; low‐certainty evidence). SAE evidence was limited by imprecision. We found no data on neuropsychiatric or cardiac SAEs. We found high‐certainty evidence that varenicline helps more people to quit than placebo (RR 2.32, 95% CI 2.15 to 2.51; I 2 = 60%, 41 studies, 17,395 participants), and moderate‐certainty evidence that people taking varenicline are more likely to report SAEs than those not taking it (RR 1.23, 95% CI 1.01 to 1.48; I 2 = 0%; 26 studies, 14,356 participants). While point estimates suggested increased risk of cardiac SAEs (RR 1.20, 95% CI 0.79 to 1.84; I 2 = 0%; 18 studies, 7151 participants; low‐certainty evidence), and decreased risk of neuropsychiatric SAEs (RR 0.89, 95% CI 0.61 to 1.29; I 2 = 0%; 22 studies, 7846 participants; low‐certainty evidence), in both cases evidence was limited ...

Cytisinicline for Smoking Cessation

“…The effect size and absolute level of tobacco abstinence achieved with cytisinicline at 6-month follow-up in this trial were larger than the continuous 6-month abstinence rate in a previous placebo-controlled trial that used the drug’s traditional dosing and in a recent systematic review of cytisinicline clinical trials . This supports the hypothesis that a higher dose and longer treatment duration increases cytisinicline’s efficacy while maintaining acceptable tolerability.…”

Cytisinicline for Vaping Cessation in Adults Using Nicotine E-Cigarettes

“…Cytisinicline’s low adverse effect profile (especially nausea) may lead to high treatment adherence and facilitate successful quit attempts. Furthermore, the efficacy of cytisinicline for smoking cessation suggests that it might be a treatment option for individuals seeking to quit both smoking and vaping (dual users).…”

“…Cytisinicline, a partial agonist at α4β2 nicotinic acetylcholine receptors that mediate nicotine dependence, has shown efficacy for cigarette smoking cessation . Because cytisinicline use is associated with reduced nicotine dependence, we hypothesized that the medication would also help adults to quit vaping nicotine.…”

Predictive Insights Into Exocrine Pancreatic Insufficiency in Chronic Pancreatitis and Autoimmune Pancreatitis

“…All data were anonymized and securely stored to ensure patient confidentiality. Brinkman Index, homeostatic model assessment of β-cell function (HOMA-β), homeostatic model assessment of insulin resistance (HOMA-IR), fibrosis-4 index (FIB-4), and aspartate aminotransferase (AST)–to–platelet ratio index (APRI) were all calculated according to established formulae 15–17 …”