Background
Globally, in 2012, the prevalence of daily tobacco smoking among men and women aged 15 and over was 31.1% and 6.2%, respectively [
1]. Smoking seriously affects almost all organs in the body. Tobacco smoking can lead to many short- and long-term health effects including lung and other organ cancers, chronic bronchitis, emphysema, stroke, and heart attack [
2]. Tobacco smoking is responsible for 90% of all cases of lung cancer and 90% of all deaths due to chronic obstructive pulmonary disease (COPD) [
3]. According to the World Health Organization, tobacco smoking kills about six million people globally per annum [
4]. Second-hand smoke contains hundreds of chemicals responsible for diseases such as respiratory disorders, cancer, and cardiovascular disease. Combustible chemicals found in tobacco smoke are responsible for disorders such as cancer, cardiovascular, and pulmonary diseases, through mechanisms that involve DNA damage, inflammation, and oxidative stress [
5]. Globally, second-hand smoking affects women and children more than men [
6,
7]. Tobacco-related disability-adjusted life years (DALYs) account for 4% of the global burden with the burden significantly higher for developed nations [
8].
Tobacco contains about 4000 chemicals; nicotine is one of the chemicals contained in tobacco, and it is responsible for addictive behavior [
9]. During smoking, the nicotine components are absorbed through the mucous membrane and enter the brain through the bloodstream. Upon entering the brain, nicotine stimulates the release of epinephrine and dopamine which in turn increases blood pressure, heartbeat, and respiration rate and produces pleasurable feelings [
3,
9].
In the long term, smoking cessation can decrease the risk of cancer, stroke, and heart attacks and can also improve survival [
3,
10]. Smoking cessation can also decrease the risk of respiratory infections such as pneumonia, influenza, and chronic obstructive pulmonary disease. [
11]. Kahler et al. and Eddy et al. have shown that quitting smoking is associated with significant reductions in risk of COPD, myocardial infarctions, stroke, and coronary heart disease [
12,
13]. Moreover, smoking cessation can improve health-related quality of life (physical, psychological, and social functioning in relation to health) [
14].
A range of smoking cessation interventions is available which can be broadly categorized as motivational, behavioral/psychological, and pharmacological. The World Health Organization recommends that countries prioritize different smoking cessation strategies depending on their available resources, national health system, and political will to implement the cessation strategies [
15]. Treatment of tobacco smoking, like any other forms of substance dependence, necessitates pharmacological interventions to minimize cravings and the treatment of withdrawal symptoms associated with nicotine dependence [
9]. Nicotine replacement therapies (NRT) in different formulations such as inhalation, patches, gums, nasal sprays, and lozenges can be used for treatment of withdrawal symptoms after smoking cessation. Since the nicotine concentration in NRT is low compared to tobacco, it has a low addiction rate [
3].
Amfebutamone (bupropion) represents the first non-nicotine drug used for the treatment of nicotine dependence. Amfebutamone works by antagonizing nicotine receptors and inhibits the reuptake of epinephrine, dopamine, and serotonin, thus reducing withdrawal symptoms [
16‐
18]. Varenicline is a nicotine receptor partial agonist that blocks nicotine receptors by binding into α
4β
2 nicotinic acetylcholine receptors and moderately releases dopamine, thus reducing the craving and withdrawal symptoms associated with an absence of nicotine [
19].
The success of smoking cessation was associated with factors such as male gender, smoking frequency, alcohol dependence, a household ban on smoking, living with a smoker, and having close friends who smoke [
20,
21]. The most common adverse effects of NRT include insomnia, headache, vomiting, dizziness, palpitation, anxiety, and depression. Bupropion and varenicline are also associated with side effects like insomnia, dry mouth, agitation, and nausea [
22,
23]. A systematic review identified a positive relationship between weight gain and smoking cessation [
24]. Researchers have recommended the importance of weight management interventions along with smoking cessation interventions [
25]. There are enzymes produced as a result of cigarette smoking responsible for the metabolism of drugs like clozapine. Therefore, smoking cessation can lead to a toxic side effect as a result of an increase in drug plasma concentration and requires monitoring and reduction in the dose of drugs [
26].
Although most of the previous trials and systematic reviews confirmed the effectiveness of behavioral interventions [
27,
28] for smoking cessation, the findings are not consistent for pharmacological interventions. Therefore, the proposed umbrella review will provide a summary of the evidence on the effectiveness of different types of pharmacotherapy. To date, many trials and systematic reviews have been conducted to assess the effectiveness of pharmacotherapy for smoking cessation. The proposed umbrella review of existing systematic reviews will present evidence from previous systematic reviews to help inform decision-makers and clinicians.
Objectives
The proposed umbrella review will synthesize findings of previous reviews in order to evaluate the effects of different pharmacotherapies for smoking cessation and assess consistency of conclusions among previous systematic reviews. The proposed umbrella review will summarize the effects of pharmacological interventions reported by each review of smoking cessation, specifically addressing the following objectives:
-
To summarizing existing systematic reviews that assessed the effects of pharmacological interventions for smoking cessation
-
To assess the methodological quality of previously conducted systematic reviews
Discussion
Systematic reviews are considered as an important source of information for clinicians and policy makers because combining the findings from a series of studies can provide a more accurate and reliable evidence base through improved statistical power. Moreover, systematic reviews are an important tool for the development of guidelines and strategies for medical practice and suggesting directions for new research [
37,
38]. Clinicians and decision-makers need to assure themselves that the basic approaches and methods used to collect and combine the findings of individual studies are relevant and sound before using the evidence for patient care and policy development [
38,
39]. Review of systematic reviews help as a method to providing a higher level combination of evidence to wide public health problems [
40].
The World Health Organization recommends including treatment of tobacco dependence as one strategy of its comprehensive tobacco-control policy, along with measures such as taxation and price policies, advertising restrictions, dissemination of information, and establishment of smoke-free public places [
15]. Therefore, in the proposed review of reviews, we will be summarizing existing systematic reviews that assessed the effects of pharmacological interventions for smoking cessation and also conduct methodological quality of the included reviews. The findings of our review will improve clinical decision-making and will be used as a baseline for future studies.