Smoking cessation - Emerging treatments

Cytisinicline (cytisine)

A plant derivative, cytisinicline (also known as cytisine) is a partial agonist at the alpha-4 beta-2 nicotinic acetylcholine receptor, with a similar mechanism of action to varenicline. Evidence for cytisinicline looks very promising, and suggests that it may be more effective than single-agent nicotine replacement therapy (NRT) as well as placebo.[127][197][198] Results from one phase 3 randomised controlled trial (RCT) suggest that 32.6% of people randomised to receive 12 weeks of cytisinicline were abstinent during weeks 9-12 of treatment (compared with 7.0% in the placebo group), and 21.1% were abstinent during weeks 9-24 (compared with 4.8% in the placebo control group).[198] Adverse effects included nausea, headache, and insomnia, with 2.9% of study participants discontinuing the drug due to tolerability problems. One Cochrane review found cytisinicline to be similar in efficacy to varenicline.[125] Cytisinicline has a long history of use in Eastern Europe, but its use is limited across most of Europe, and it has not received US Food and Drug Administration (FDA) or European Medicines Agency (EMA) approval, although the FDA has granted breakthrough designation to the drug in order to expedite its review and approval. However, it is approved for use in the UK by the Medicines and Healthcare products Regulatory Agency (MHRA), and is recommended by the National Institute for Health and Care Excellence (NICE) in the UK as one of a number of options for smoking cessation when combined with behavioural support. Healthcare professionals are encouraged to discuss the available options with patients to determine the most suitable treatment based on individual needs and preferences. Regarding the decision to recommend cytisinicline, the NICE committee states that, despite moderate to very low-quality evidence, cytisinicline appears to be effective for smoking cessation with behavioural support, outperforming placebo and NRT, and demonstrating similar effectiveness to varenicline. Cytisinicline is only recommended for those between the ages of 18 and 65 years, and is not recommended during pregnancy or breastfeeding. NICE advises setting a stopping date within the first 5 days of treatment.[63]

Pharmacogenetics

Association studies on genetic polymorphisms and smoking cessation following NRT and/or bupropion therapy have been carried out, but only a few candidate genes or regions were analysed, requiring further research.[54][199] Evidence to support the use of pharmacogenetic tests in routine smoking cessation therapy is still lacking, though continuously growing.[200]

Nicotine vaccine

Antibodies formed against nicotine may prevent this molecule from crossing to the reward centres of the brain, and thereby prevent the positive reinforcing effects of smoking. To be effective, high antibody levels would need to be achieved and maintained. Early studies suggested that three vaccines in testing were safe and well tolerated. In a randomised trial, nicotine-Q beta has been shown to increase 12-month cessation rates in smokers in the highest tertile of antibody response compared with those who received placebo.[201] However, overall cessation rates were not different between vaccinated and placebo groups.[201] To date, no nicotine vaccines have enhanced long-term smoking cessation. There has been no further development in recent years, and it may be that nicotine vaccines are no longer under active investigation.

Transcranial magnetic stimulation

Animal models have shown that repeated transcranial magnetic stimulation (TMS) of the dorsal prefrontal cortex can cause lasting reductions in drug craving and consumption. One small study suggested that application of high-frequency TMS treatment reduced nicotine consumption and dependence, yielding a 33% abstinence rate at 6-month follow-up.[202] One larger multicentre, double-blind RCT suggested that abstinence was achieved in 28% of participants compared with 11.7% in the sham group.[203] The FDA has given marketing clearance to one particular device using TMS as an aid for short-term smoking cessation in adults. It is currently unclear whether there is a particular subsection of people who are more likely to benefit from treatment.[204]

Alternative therapies

Several alternative therapies have been advertised for smoking cessation, most in an anecdotal fashion. One Cochrane database review for hypnotherapy, for example, reviewed 14 studies and suggested that there is insufficient evidence to determine whether hypnotherapy is more effective for smoking cessation than other forms of behavioural support or unassisted stopping.[205] One meta-analysis of 24 trials looking at acupuncture for smoking cessation suggested a statistically significant abstinence rate with acupuncture versus no intervention, but there was no statistically significant comparison between real acupuncture and sham acupuncture, suggesting a placebo effect.[206] One RCT using 8 weeks of yoga therapy compared with general wellness classes as controls showed a statistically significant improvement in abstinence rates up to 6 months later in a dose-response manner, presenting an interesting potential adjunct to treatment.[207] However, one systematic review found no clear benefit or harm of yoga on stopping rates.[208]