Nicotine replacement therapy versus control for smoking cessation

  • Review
  • Intervention




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.

Search methods

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.

Selection criteria

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.

Data collection and analysis

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.

Main results

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.

Authors' conclusions

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.

Plain language summary

Can nicotine replacement therapy (NRT) help people quit smoking?


We reviewed the evidence about whether NRT helps people who want to quit smoking to stop smoking at six months or longer. NRT aims to reduce withdrawal symptoms associated with stopping smoking by replacing the nicotine from cigarettes. NRT is available as skin patches that deliver nicotine slowly, and chewing gum, nasal and oral sprays, inhalators, and lozenges/tablets, all of which deliver nicotine to the brain more quickly than skin patches, but less rapidly than from smoking cigarettes.

Study characteristics

This review includes 136 trials of NRT, with 64,640 people in the main analysis. All studies were conducted in people who wanted to quit smoking. Most studies were conducted in adults and had similar numbers of men and women. Six studies were conducted in pregnant women. People enrolled in the studies typically smoked at least 15 cigarettes a day at the start of the studies. The evidence is current to July 2017. Trials lasted for at least six months, except for two in pregnant women which ended at the time of delivery.

Key results

We found evidence that all forms of NRT made it more likely that a person's attempt to quit smoking would succeed. The chances of stopping smoking were increased by 50% to 60%. NRT works with or without additional counselling, and does not need to be prescribed by a doctor. Side effects from using NRT are related to the type of product, and include skin irritation from patches and irritation to the inside of the mouth from gum and tablets. There is no evidence that NRT increases the risk of heart attacks. In pregnant women, evidence suggests that NRT can increase the chance of quitting at the time of delivery.

Quality of evidence

The overall quality of the evidence is high, meaning that further research is very unlikely to change our conclusions.

Ringkasan bahasa mudah

Bolehkah terapi penggantian nikotina (NRT) bantu perokok berhenti merokok?

Latar belakang

Kami mengkaji bukti sama ada NRT membantu perokok yang ingin berhenti merokok untuk berhenti merokok pada enam bulan atau lebih lama. NRT bertujuan untuk mengurangkan gejala sarak yang dikaitkan dengan pemberhentian merokok melalui penggantian nikotina daripada rokok. NRT boleh didapati dalam bentuk tampalan di kulit yang membekalkan nikotina secara perlahan, dan gula-gula getah, semburan hidung dan oral/mulut, sedutan, dan ‘lozenges’/biji-biji pil, kesemuanya membekalkan nikotina ke otak lebih cepat dari tampalan di kulit, tetapi lebih perlahan berbanding dari menghisap rokok.

Ciri-ciri kajian

Ulasan ini melibatkan 136 kajian NRT, dengan 64,640 orang di dalam analisis utama. Semua kajian dijalankan dalam orang yang ingin berhenti merokok. Kebanyakan kajian dijalankan dalam kalangan orang dewasa dan mempunyai bilangan lelaki dan wanita yang agak sama. Enam kajian dijalankan dalam wanita hamil. Orang yang didaftarkan dalam kajian kebiasaannya menghisap sekurang-kurangnya 15 batang rokok sehari pada permulaan kajian. Bukti adalah terkini sehingga Julai 2017. Kajian adalah selama sekurang-kurangnya enam bulan, kecuali untuk dua dalam wanita hamil yang berakhir pada masa kelahiran.

Keputusan-keputusan utama

Kami mendapati bukti bahawa kesemua bentuk NRT menjadikannya lebih berkemungkinan berjaya percubaan seseorang untuk berhenti merokok. Peluang untuk berhenti merokok telah meningkat sebanyak 50% hingga 60%. NRT berjaya dengan atau tanpa kaunseling tambahan, dan tidak perlu diberi preskripsi oleh doktor. Kesan-kesan sampingan daripada penggunaan NRT mempunyai kaitan dengan jenis produk, dan termasuk kerengsaan kulit daripada tampalan-tampalan dan kerengsaan pada bahagian dalam mulut daripada gula-gula getah dan tablet / biji-biji pil. Tiada bukti bahawa NRT meningkatkan risiko serangan jantung. Dalam kalangan wanita hamil, bukti mencadangkan NRT boleh meningkatkan peluang untuk pemberhentian pada masa kelahiran.

Kualiti bukti

Kualiti keseluruhan bukti adalah tinggi, bermakna penyelidikan selanjutnya tidak mungkin mengubah kesimpulan kami.

Catatan terjemahan

Diterjemahkan oleh Noor Salwah S Omar (Universiti Sains Malaysia). Disunting oleh Tuan Hairulnizam Tuan Kamauzaman (Universiti Sains Malaysia). Untuk sebarang pertanyaan berkaitan terjemahan sila hubungi