Nicotine receptor partial agonists for smoking cessation.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of randomized controlled trials
PubMed 27158893 · doi:10.1002/14651858.CD006103.pub7
What was done
The authors systematically reviewed randomized controlled trials from the Cochrane Tobacco Addiction Group register, MEDLINE, EMBASE, PsycINFO, and clinical trials databases through May 2015 (plus subsequent key trials) evaluating nicotine receptor partial agonists (varenicline, cytisine, dianicline) for smoking cessation. Eligible trials required a minimum 6-month follow-up. The primary outcome was continuous or sustained smoking abstinence at longest follow-up (preferring biochemically validated rates), pooled using Mantel-Haenszel fixed-effect risk ratios (RRs).
What was found
- Cytisine vs placebo: RR 3.98 (95% CI 2.01 to 7.87; 2 trials, 937 participants; low-quality evidence). - Cytisine vs NRT: RR 1.43 (95% CI 1.13 to 1.80; 1 trial, 1310 participants at 6 months). - Dianicline vs placebo: RR 1.20 (95% CI 0.82 to 1.75; 1 trial, 602 participants; development discontinued). - Varenicline (standard dose) vs placebo: RR 2.24 (95% CI 2.06 to 2.43; 27 trials, 12,625 participants; high-quality evidence; number needed to treat = 11, 95% CI 9 to 13). Lower/variable doses were also effective (RR 2.08, 95% CI 1.56 to 2.78; 4 trials, 1266 participants). - Varenicline vs bupropion: RR 1.39 (95% CI 1.25 to 1.54; 5 trials, 5877 participants; high-quality evidence). - Varenicline vs NRT: RR 1.25 (95% CI 1.14 to 1.37; 8 trials, 6264 participants at 24 weeks; moderate-quality evidence). - Adverse events: Nausea was the most common side effect of varenicline. Serious adverse events showed a small increase with varenicline (RR 1.25, 95% CI 1.04 to 1.49; 29 trials, 15,370 participants), though most were judged unrelated to treatment and control group loss to follow-up was higher.
Why it matters
Varenicline is an effective pharmacotherapy that outperforms bupropion and nicotine replacement therapy for long-term smoking cessation. Cytisine also demonstrates clear efficacy and provides an alternative partial agonist option.
Limits
Cytisine evidence was limited to few trials and rated as low-quality for placebo comparison. Differential loss to follow-up between study arms likely led to underascertainment of serious adverse events in control groups. The evidence was not conclusive regarding neuropsychiatric safety in individuals with past or current psychiatric disorders, and cardiovascular safety in high-risk groups remains unresolved pending dedicated trial data.
Cited by
- supports Varenicline yields a 20% to 30% abstinence rate for smoking cessation.