Pharmacological interventions for smoking cessation: an overview and network meta-analysis.

Background Smoking is a main cause of early death throughout the world. There are a number of medications which can help people to quit smoking. Three of these, nicotine replacement therapy (NRT), bupropion and varenicline, are licensed for this purpose in the USA and Europe. Cytisine (similar to varenicline) is licensed for use in Russia and Eastern Europe. We reviewed studies of these and other treatments, including nortriptyline, to compare their benefits and risks. Methods We found 12 Cochrane reviews of different treatments. The treatments include nicotine replacement therapy (NRT); antidepressants (bupropion and nortriptyline); nicotine receptor partial agonists (varenicline and cytisine); anxiolytics; selective type 1 cannabinoid receptor antagonists (rimonabant); clonidine; lobeline; dianicline; mecamylamine; Nicobrevin; opioid antagonists; nicotine vaccines; and silver acetate. The reviews were conducted between 2008 and 2012, and analysed 267 trials, covering more than 101,000 smokers. All the reviews used randomised controlled trials, and compared the active treatment with a placebo, and sometimes with other treatments. The outcomes were measured at least six months from the start of treatment, and the results were usually checked by testing breath, blood or urine. We also assessed the risk of harms from each treatment. We then compared NRT, bupropion and varenicline with each other, using a network meta-analysis. Results NRT and bupropion helped about 80% more people to quit than placebo; this means that for every 10 people who quit with placebo about 18 could be expected to quit with NRT or with bupropion. Varenicline more than doubled the chances of quitting compared with placebo, so that for every 10 who quit with placebo about 28 could be expected to quit with varenicline. Varenicline helped about 50% more people to quit than nicotine patch and 'other' NRT (tablets, sprays, lozenges and inhalers), and about 70% more people than nicotine gum. So for every 10 people who quit with NRT patch or with 'other' NRT, about 15 could be expected to quit with varenicline, and for every 10 who quit with NRT gum about 17 could be expected to quit with varenicline. Combining two type of NRT was as effective as using varenicline, and helped more people to quit than single types of NRT. There was little to choose between different types of NRT, apart from 'other' NRT, which helped slightly more people than nicotine gum; for every 10 people who quit with NRT gum, about 12 could be expected to quit with 'other' NRT. NRT combined with nortriptyline or with bupropion was not more effective than NRT alone. Both cytisine and nortriptyline compared with placebo improved the chances of quitting, with minimal risk of harms. Bupropion carries a known risk of seizures (about 1 per 1000 users), but we found fewer than expected in the included and excluded trials, at about 1 in 1500. Although there may be a marginal increase in the likelihood of any serious adverse event while taking bupropion, we did not find increased risks of neuropsychiatric or heart and circulatory problems in the bupropion studies. The evidence for the safety of varenicline is still under investigation; we found no evidence from the trials that it is linked to an increase in neuropsychiatric problems, or with increased heart and circulatory problems. Clonidine helped people to quit, but caused side effects. It is not clear whether or not mecamylamine used with NRT helps people to quit. Other treatments did not seem to help. So far, nicotine vaccines are not licensed for use anywhere in the world. Nicobrevin is no longer available in the UK, and rimonabant, taranabant and dianicline have all been withdrawn from the market. Conclusions • NRT, bupropion and varenicline all improve the chances of quitting, with a low risk of harms. • Combination use of NRT is as effective as varenicline, and more effective than single types of NRT. • Cytisine has potential as a safe, effective and affordable treatment. • Nortriptyline improves the chances of quitting, with little evidence of harmful events. • We need continued monitoring of the safety of varenicline. • More research into NRT versus placebo is unlikely to change our understanding of the treatment.

Pharmacotherapy of Tobacco Use Disorder

Nicotine replacement therapy (NRT) aims to temporarily replace much of the nicotine from cigarettes to reduce motivation to smoke and nicotine withdrawal symptoms, thus easing the transition from cigarette smoking to complete abstinence. To determine the effectiveness and safety of nicotine replacement therapy (NRT), including gum, transdermal patch, intranasal spray and inhaled and oral preparations, for achieving long-term smoking cessation, compared to placebo or 'no NRT' interventions. We searched the Cochrane Tobacco Addiction Group trials register for papers mentioning 'NRT' or any type of nicotine replacement therapy in the title, abstract or keywords. Date of most recent search is July 2017. Randomized trials in people motivated to quit which compared NRT to placebo or to no treatment. We excluded trials that did not report cessation rates, and those with follow-up of less than six months, except for those in pregnancy (where less than six months, these were excluded from the main analysis). We recorded adverse events from included and excluded studies that compared NRT with placebo. Studies comparing different types, durations, and doses of NRT, and studies comparing NRT to other pharmacotherapies, are covered in separate reviews. Screening, data extraction and 'Risk of bias' assessment followed standard Cochrane methods. The main outcome measure was abstinence from smoking after at least six months of follow-up. We used the most rigorous definition of abstinence for each trial, and biochemically validated rates if available. We calculated the risk ratio (RR) for each study. Where appropriate, we performed meta-analysis using a Mantel-Haenszel fixed-effect model. We identified 136 studies; 133 with 64,640 participants contributed to the primary comparison between any type of NRT and a placebo or non-NRT control group. The majority of studies were conducted in adults and had similar numbers of men and women. People enrolled in the studies typically smoked at least 15 cigarettes a day at the start of the studies. We judged the evidence to be of high quality; we judged most studies to be at high or unclear risk of bias but restricting the analysis to only those studies at low risk of bias did not significantly alter the result. The RR of abstinence for any form of NRT relative to control was 1.55 (95% confidence interval (CI) 1.49 to 1.61). The pooled RRs for each type were 1.49 (95% CI 1.40 to 1.60, 56 trials, 22,581 participants) for nicotine gum; 1.64 (95% CI 1.53 to 1.75, 51 trials, 25,754 participants) for nicotine patch; 1.52 (95% CI 1.32 to 1.74, 8 trials, 4439 participants) for oral tablets/lozenges; 1.90 (95% CI 1.36 to 2.67, 4 trials, 976 participants) for nicotine inhalator; and 2.02 (95% CI 1.49 to 2.73, 4 trials, 887 participants) for nicotine nasal spray. The effects were largely independent of the definition of abstinence, the intensity of additional support provided or the setting in which the NRT was offered. A subset of six trials conducted in pregnant women found a statistically significant benefit of NRT on abstinence close to the time of delivery (RR 1.32, 95% CI 1.04 to 1.69; 2129 participants); in the four trials that followed up participants post-partum the result was no longer statistically significant (RR 1.29, 95% CI 0.90 to 1.86; 1675 participants). Adverse events from using NRT were related to the type of product, and include skin irritation from patches and irritation to the inside of the mouth from gum and tablets. Attempts to quantitatively synthesize the incidence of various adverse effects were hindered by extensive variation in reporting the nature, timing and duration of symptoms. The odds ratio (OR) of chest pains or palpitations for any form of NRT relative to control was 1.88 (95% CI 1.37 to 2.57, 15 included and excluded trials, 11,074 participants). However, chest pains and palpitations were rare in both groups and serious adverse events were extremely rare. There is high-quality evidence that all of the licensed forms of NRT (gum, transdermal patch, nasal spray, inhalator and sublingual tablets/lozenges) can help people who make a quit attempt to increase their chances of successfully stopping smoking. NRTs increase the rate of quitting by 50% to 60%, regardless of setting, and further research is very unlikely to change our confidence in the estimate of the effect. The relative effectiveness of NRT appears to be largely independent of the intensity of additional support provided to the individual. Provision of more intense levels of support, although beneficial in facilitating the likelihood of quitting, is not essential to the success of NRT. NRT often causes minor irritation of the site through which it is administered, and in rare cases can cause non-ischaemic chest pain and palpitations.

There is high-certainty evidence that using combination NRT versus single-form NRT, and 4 mg versus 2 mg nicotine gum, can increase the chances of successfully stopping smoking. For patch dose comparisons, evidence was of moderate certainty, due to imprecision. Twenty-one mg patches resulted in higher quit rates than 14 mg (24-hour) patches, and using 25 mg patches resulted in higher quit rates than using 15 mg (16-hour) patches, although in the latter case the CI included one. There was no clear evidence of superiority for 42/44 mg over 21/22 mg (24-hour) patches. Using a fast-acting form of NRT, such as gum or lozenge, resulted in similar quit rates to nicotine patches. There is moderate-certainty evidence that using NRT prior to quitting may improve quit rates versus using it from quit date only; however, further research is needed to ensure the robustness of this finding. Evidence for the comparative safety and tolerability of different types of NRT use is of low and very low certainty. New studies should ensure that AEs, SAEs and withdrawals due to treatment are both measured and reported.

Aim. This review compared the effect of high-dose nicotine replacement therapy (NRT) and combinations of NRT for increasing smoking abstinence rates compared to standard-dose NRT patch, varenicline, and bupropion on smoking abstinence.Methods. Ten electronic databases were searched (up to January 2012) for randomized controlled trials (RCT) of standard-dose (≤ 22 mg) or high-dose nicotine patch therapy (> 22 mg), combination NRT (e.g. nicotine patch + nicotine inhaler), bupropion, and varenicline. Analysis consisted of random-effects pairwise meta-analysis and a Bayesian multiple treatment comparison (MTC).Results. We identified 146 RCTs (65 standard-doses of the nicotine patch (≤ 22 mg); 6 high-dose NRT patch (> 22 mg); 5 high versus standard-dose NRT patch; 5 combination NRT versus inert controls; 6 combination versus single NRT patch; 48 bupropion; and 11 varenicline). The MTC found that all therapies offered treatment benefits at most time points over controls. Combination NRT and higher-dose NRT did not demonstrate consistent effects over other interventions. With the exception of varenicline, the benefits of treatments over standard-dose NRT were not retained in the long term.Conclusions. All pharmacologic treatments were significantly more effective than inert controls. Varenicline was the only treatment demonstrating effects over other options. These results should be considered in the development of clinical practice guidelines.

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). OBJECTIVES: To review the efficacy of nicotine receptor partial agonists, including varenicline and cytisine, for smoking cessation. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group's specialised register for trials, using the terms ('cytisine' or 'Tabex' or 'dianicline' or 'varenicline' or 'nicotine receptor partial agonist') in the title or abstract, or as keywords. The register is compiled from searches of MEDLINE, EMBASE, and PsycINFO using MeSH terms and free text to identify controlled trials of interventions for smoking cessation and prevention. We contacted authors of trial reports for additional information where necessary. The latest update of the specialised register was in May 2015, although we have included a few key trials published after this date. We also searched online clinical trials registers. SELECTION CRITERIA: We included randomised controlled trials which compared the treatment drug with placebo. We also included comparisons with bupropion and nicotine patches where available. We excluded trials which did not report a minimum follow-up period of six months from start of treatment. DATA COLLECTION AND ANALYSIS: We extracted data on the type of participants, the dose and duration of treatment, the outcome measures, the randomisation procedure, concealment of allocation, and completeness of follow-up.The main outcome measured was abstinence from smoking at longest follow-up. We used the most rigorous definition of abstinence, and preferred biochemically validated rates where they were reported. Where appropriate we pooled risk ratios (RRs), using the Mantel-Haenszel fixed-effect model. MAIN RESULTS: Two trials of cytisine (937 people) found that more participants taking cytisine stopped smoking compared with placebo at longest follow-up, with a pooled risk ratio (RR) of 3.98 (95% confidence interval (CI) 2.01 to 7.87; low-quality evidence). One recent trial comparing cytisine with NRT in 1310 people found a benefit for cytisine at six months (RR 1.43, 95% CI 1.13 to 1.80).One trial of dianicline (602 people) failed to find evidence that it was effective (RR 1.20, 95% CI 0.82 to 1.75). This drug is no longer in development.We identified 39 trials that tested varenicline, 27 of which contributed to the primary analysis (varenicline versus placebo). Five of these trials also included a bupropion treatment arm. Eight trials compared varenicline with nicotine replacement therapy (NRT). Nine studies tested variations in varenicline dosage, and 13 tested usage in disease-specific subgroups of patients. The included studies covered 25,290 participants, 11,801 of whom used varenicline.The pooled RR for continuous or sustained abstinence at six months or longer for varenicline at standard dosage versus placebo was 2.24 (95% CI 2.06 to 2.43; 27 trials, 12,625 people; high-quality evidence). Varenicline at lower or variable doses was also shown to be effective, with an RR of 2.08 (95% CI 1.56 to 2.78; 4 trials, 1266 people). The pooled RR for varenicline versus bupropion at six months was 1.39 (95% CI 1.25 to 1.54; 5 trials, 5877 people; high-quality evidence). The RR for varenicline versus NRT for abstinence at 24 weeks was 1.25 (95% CI 1.14 to 1.37; 8 trials, 6264 people; moderate-quality evidence). Four trials which tested the use of varenicline beyond the 12-week standard regimen found the drug to be well-tolerated during long-term use. The number needed to treat with varenicline for an additional beneficial outcome, based on the weighted mean control rate, is 11 (95% CI 9 to 13). The most commonly reported adverse effect of varenicline was nausea, which was mostly at mild to moderate levels and usually subsided over time. Our analysis of reported serious adverse events occurring during or after active treatment suggests there may be a 25% increase in the chance of SAEs among people using varenicline (RR 1.25; 95% CI 1.04 to 1.49; 29 trials, 15,370 people; high-quality evidence). These events include comorbidities such as infections, cancers and injuries, and most were considered by the trialists to be unrelated to the treatments. There is also evidence of higher losses to follow-up in the control groups compared with the intervention groups, leading to a likely underascertainment of the true rate of SAEs among the controls. Early concerns about a possible association between varenicline and depressed mood, agitation, and suicidal behaviour or ideation led to the addition of a boxed warning to the labelling in 2008. However, subsequent observational cohort studies and meta-analyses have not confirmed these fears, and the findings of the EAGLES trial do not support a causal link between varenicline and neuropsychiatric disorders, including suicidal ideation and suicidal behaviour. The evidence is not conclusive, however, in people with past or current psychiatric disorders. Concerns have also been raised that varenicline may slightly increase cardiovascular events in people already at increased risk of those illnesses. Current evidence neither supports nor refutes such an association, but we await the findings of the CATS trial, which should establish whether or not this is a valid concern. AUTHORS' CONCLUSIONS: Cytisine increases the chances of quitting, although absolute quit rates were modest in two recent trials. Varenicline at standard dose increased the chances of successful long-term smoking cessation between two- and three-fold compared with pharmacologically unassisted quit attempts. Lower dose regimens also conferred benefits for cessation, while reducing the incidence of adverse events. More participants quit successfully with varenicline than with bupropion or with NRT. Limited evidence suggests that varenicline may have a role to play in relapse prevention. The most frequently recorded adverse effect of varenicline is nausea, but mostly at mild to moderate levels and tending to subside over time. Early reports of possible links to suicidal ideation and behaviour have not been confirmed by current research.Future trials of cytisine may test extended regimens and more intensive behavioural support.

Objective To determine the effectiveness and safety of nicotine replacement therapy assisted reduction to stop smoking.Design Systematic review of randomised controlled trials.Data sources Cochrane Library, Medline, Embase, CINAHL, PsychINFO, Science...

Gender, smoking status, and risk behavior attitudes explain adolescents' patterns of nicotine replacement therapy use

Comparative efficacy and safety of pharmacological interventions for smoking cessation in healthy adults: A network meta-analysis

Background and objectiveRelative effectiveness of smoking cessation medications—varenicline, bupropion and nicotine replacement therapy (NRT)—remains unclear among smokers in real-world settings. Evidence in females and smokers with light/moderate nicotine dependence is particularly insufficient. This study compared the effectiveness of varenicline, bupropion or NRT gum relative to NRT patch, in achieving abstinence among recent quitters.MethodsIn a national smoking cessation program in Taiwan (2012–2015), a cohort of 11,968 participants received varenicline (n = 5,052), bupropion (n = 823), NRT gum (n = 1944) or NRT patch (n = 4,149). The 7-day, 1-month or 6-month point-prevalence was calculated based on self-reported last smoking event via telephone interview after 6 months. Logistic regression modellings estimated odds ratios (OR) and 95% confidence intervals (CI) for achieving abstinence using different modalities (NRT patch as referent). Models included age, sex, education, marital status, geographic region, smoke-years, nicotine-dependence level, medical institution, number of clinic visits and medication use duration. Analyses were further stratified by sex and dependence severity.ResultsParticipants were predominantly male (83%) with a mean age of 43.7±12.6 years. Varenicline users were more likely than NRT patch users to achieve abstinence, based on 7-day point-prevalence (OR = 1.30, CI: 1.19–1.44), 1-month point-prevalence (OR = 1.36, CI: 1.24–1.50) or 6-month point-prevalence (OR = 1.30, CI: 1.14–1.47). Compared with NRT patch, varenicline was associated with greater odds of being abstinent in women (OR = 1.29, CI: 1.01–1.65), men (OR = 1.31, CI: 1.18–1.46), those with light/moderate dependence (OR = 1.42, CI: 1.24–1.63) or smokers with severe dependence (OR = 1.19, CI: 1.04–1.37), based on 7-day point-prevalence. Differences in effectiveness were not observed between users of bupropion, NRT gum and NRT patch.ConclusionsIn smoking cessation clinics in Taiwan, varenicline users reported higher abstinence rates than NRT patch users after 6 months. Women and smokers with light/moderate nicotine dependence may also benefit from varenicline in actual clinical practice.

Cigarette smoking and risky alcohol consumption co-occur and are undertreated. Nicotine receptor partial agonists and nicotine replacement therapy (NRT) treat smoking but are unproven for alcohol, and clinical trials rarely include individuals with HIV, substance use, and mental health conditions. To compare the effects on drinking and smoking of nicotinic acetylcholine receptor partial agonists varenicline and cytisine with those of NRT. This 4-group randomized, double-blinded, placebo-controlled clinical trial was conducted from July 2017 to December 2020 in St Petersburg, Russia. Included participants were 400 individuals with HIV who engaged in risky drinking (≥5 prior-month heavy-drinking days [HDDs]) and daily smoking; they were followed up for 12 months after enrollment. Data were analyzed from May 2021 through June 2022. Participants received alcohol and tobacco counseling, 1 active medication, and 1 placebo in 1 of 4 groups: active varenicline and placebo NRT (group 1), placebo varenicline and active NRT (group 2), active cytisine and placebo NRT (group 3), or placebo cytisine and active NRT (group 4). The primary outcome was number of prior-month HDDs at 3 months. Secondary outcomes included biochemically validated abstinence from alcohol at 3 months and smoking at 6 months. Among 400 participants (263 [65.8%] men; mean [SD] age, 39 [6] years), 97 individuals (24.3%) used opioids and 156 individuals (39.1%) had depressive symptoms. These individuals had a mean (SD) CD4 count of 391 (257) cells/mm3, smoked a mean (SD) of 21 [8] cigarettes/d, and reported a mean (SD) of 9.3 (5.8) HDDs in the prior 30 days. At 3 months, the mean (SD) number of HDDs was decreased vs baseline across all groups (group 1: 2.0 [3.8] HDDs vs. 9.5 [6.1] HDDs; group 2: 2.1 [4.3] HDDs vs 9.3 [5.7] HDDs; group 3: 1.5 [3.3] HDDs vs 8.9 [5.0] HDDs; group 4: 2.4 [5.2] HDDs vs 9.6 [6.3] HDDs). There were no significant differences at 3 months between groups in mean (SD) HDDs, including group 1 vs 2 (incident rate ratio [IRR], 0.94; 95% CI, 0.49-1.79), 3 vs 4 (IRR, 0.60; 95% CI, 0.30-1.18), and 1 vs 3 (IRR, 1.29; 95% CI, 0.65-2.55). There were no significant differences at 6 months between groups in smoking abstinence, including group 1 vs 2 (15 of 100 individuals [15.0%] vs 17 of 99 individuals [17.2%]; odds ratio [OR],0.89; 95% CI, 0.38-2.08), 3 vs 4 (19 of 100 individuals [19.0%] vs 19 of 101 individuals [18.8%]; OR, 1.00; 95% CI, 0.46-2.17), and 1 vs 3 (OR, 0.79; 95% CI, 0.35-1.78). Post hoc analyses suggested lower mean (SD) HDDs (eg, at 3 months: 0.7 [1.8] HDDs vs 2.3 [4.6] HDDs) and higher alcohol abstinence (eg, at 3 months: 30 of 85 individuals [35.3%] vs 54 of 315 individuals [17.1%]) among those who quit vs continued smoking. This study found that among individuals with HIV who engaged in risky drinking and smoking, varenicline and cytisine were not more efficacious than NRT to treat risky drinking and smoking but that behavior change rates were high in all groups. ClinicalTrials.gov Identifier: NCT02797587.

Nicotine replacement therapy (NRT) has been used to ameliorate nicotine withdrawal in the intensive care unit (ICU). Previous cohort studies have suggested an increased mortality with NRT use: methodological problems may call into question the validity of these findings. We undertook a retrospective cohort study to determine if NRT use was associated with adverse outcomes. This retrospective cohort study was conducted in a 30-bed, university affiliated, teaching hospital ICU. We identified 423 smokers admitted over 2 years, of whom 73 received transdermal NRT. Cox proportional hazard regression models, with NRT modelled as a time-varying covariate, were used to test the hypothesis that NRT was associated with an altered ICU or hospital mortality. A second analysis utilized propensity scores. The unadjusted ICU and hospital mortalities were lower for the NRT group; although both differences were non-significant. The Cox models showed that, after adjustment for APACHE risk, age, sex and alcohol use, risk associated with NRT administration was not statistically different than non-administration for both ICU (hazard ratio 0.50, [95 % CI 0.20-1.24], p = 0.14) and hospital (hazard ratio 0.95, [95 % CI 0.52-1.75], p = 0.88) mortality. Similar findings occurred with the propensity matched analysis. We were unable to demonstrate any harm associated with NRT, with the ICU model actually trending towards benefit. We conclude that a randomised, blinded, placebo controlled trial is required to assess adequately the safety and efficacy of NRT as a treatment in critically ill smokers.

To assess whether combining nicotine replacement therapy (NRT) with varenicline improves long-term smoking cessation rates compared with varenicline or NRT alone. Systematic review and meta-analysis of randomized controlled trials (RCTs) or quasi-RCTs, conducted according to PRISMA guidelines. A comprehensive literature search of PubMed, MEDLINE, EMBASE, Web of Science and the Cochrane Central Register of Controlled Trials was conducted through June 2025. The primary outcome was smoking abstinence at the longest follow-up (≥6 months). Secondary outcomes included adverse events (AEs) and serious adverse events (SAEs). Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using random-effects meta-analyses. The certainty of evidence was assessed using the GRADE approach. Risk of bias was assessed using the Cochrane RoB 2.0 tool. The protocol was pre-registered in the PROSPERO (registration number CRD42024600510). Seven trials including 2631 participants met inclusion criteria. Compared with varenicline alone, combination therapy was associated with statistically significantly higher abstinence rates at the longest follow-up (RR = 1.33, 95% CI = 1.04-1.69; 5 studies; I2 = 51%). A sensitivity analysis including trials with ≥3months of follow-up yielded similar results (RR = 1.31, 95% CI = 1.06-1.62; 6 studies). However, when excluding the trial at high risk of bias, the result was not statistically significant (RR = 1.26, 95% CI = 0.94-1.68). Compared with NRT alone, only one RCT was included, and the effect of combination therapy on abstinence was not statistically significant (RR = 0.94, 95% CI = 0.51-1.72). AEs were more common with combination therapy compared with varenicline alone (RR = 1.11, 95% CI = 1.02-1.20). Specifically, skin reactions were significantly increased with NRT patch plus varenicline (RR = 1.67; 95% CI = 1.29-2.16). Compared with NRT alone, combination therapy was associated with increased AEs (RR = 1.23; 95% CI = 1.07-1.41). SAEs were infrequent and generally unrelated to treatment. Low-certainty evidence indicates that combining varenicline with nicotine replacement therapy may improve long-term smoking cessation rates compared with varenicline alone and is generally well tolerated.

A number of smoking cessation pharmacotherapies have led to increases in quitting and thus to significant benefits to public health. Among existing medications, nicotine replacement therapy (NRT) has been available the longest, has the largest literature base in support, and is the only option for over-the-counter access. While the short-term efficacy of NRT is well documented in clinical trials, long-term abstinence rates associated with using NRT are modest, as most smokers will relapse. This literature review examines emerging clinical strategies to improve NRT efficacy. After an initial overview of NRT and its FDA-approved indications for use, we review randomized trials in which clinical delivery of NRT was manipulated and tested, in an attempt to enhance efficacy, through (1) duration of use (pre-quit and extended use), (2) amount of use (high-dose and combination NRT), (3) tailoring to specific smoker groups (genotype and phenotype), or (4) use of NRT for novel purposes (relapse prevention, temporary abstinence, cessation induction). Outcomes vary within and across topic area, and we highlight areas that offer stronger promise. Combination NRT likely represents the most promising strategy moving forward; other clinical strategies offer conflicting evidence but deserve further testing (pre-quit NRT or tailored treatment) or offer potential utility but are in need of further, direct tests. Some areas, though based on a limited set of studies, do not offer great promise (high-dose and extended treatment NRT). We conclude with a brief discussion of emergent NRT products (e.g., oral nicotine spray, among others), which may ultimately offer greater efficacy than current formulations. In order to further lower the prevalence of smoking, novel strategies designed to optimize NRT efficacy are needed.

BackgroundGuidance in England and Wales recommends that nicotine replacement therapies (NRTs), varenicline or bupropion should be offered for smoking cessation support. Research on general practitioner (GP) NRT prescribing patterns for smoking cessation is lacking in the published literature.MethodsUK primary care electronic health records were retrospectively analysed to identify the most common GP initiated NRT prescribing patterns, characterise people who receive NRT and determine whether NRTs given in a first quit attempt are different from subsequent attempts.ResultsThe study population comprised 38,954 individuals in UK primary care data with a first ever NRT patch smoking cessation attempt for the period January 2008-December 2011. The majority (64.3%) received NRT patch monotherapy at first smoking cessation attempt, and the most common NRT was 21 mg/24 hours patch monotherapy (15.2%). Of the 35.7% first smoking cessation attempts which were NRT combination therapy, the most common combination was patch + inhalator (56.2%). The proportion of people who started a smoking cessation attempt with combination therapy increased from 25.7% in 2008 to 44.8% in 2011. The majority of the population had one recorded smoking cessation attempt but a significant minority (20.2% N = 7,868) started a second smoking cessation attempt. Second and third attempts, while predominantly patch monotherapy, also demonstrated an increasing use of NRT combinations over the study period (2ndepisode: 20.6%-38.2%; 3rdepisode: 20.0%-36.8%). However, a minority received only non-patch NRT during second and third NRT episodes. Taking into account the 39,068 people prescribed NRT patch during the study period with a history of NRT at baseline (excluded from the analysis), the total proportion of people prescribed NRT patch between 2008–2011 who had more than one NRT episode was 48.4% (46,936/96,986) and of 128,115 NRT users, only 14.7% (N = 18,838) were prescribed bupropion or varenicline prior to NRT use.ConclusionsThe study findings represent new data describing GP NRT prescription patterns in the UK. Given the predominance of NRT patch monotherapy observed, health policy makers and service commissioners should ensure that GPs provide equality of access to all recommended smoking cessation pharmacotherapies.