Smoking Cessation Pharmacotherapy Research Articles

Investigating disparities in smoking cessation treatment for veterans with multiple sclerosis: A national analysis.

Smoking is a risk factor for multiple sclerosis (MS) development, symptom burden, decreased medication efficacy, and increased disease-related mortality. Veterans with MS (VwMS) smoke at critically high rates; however, treatment rates and possible disparities are unknown. To promote equitable treatment, we aim to investigate smoking cessation prescription practices for VwMS across social determinant factors. We extracted data from the national Veterans Health Administration electronic health records between October 1, 2017, and September 30, 2018. To derive marginal estimates of the association of MS with receipt of smoking-cessation pharmacotherapy, we used propensity score matching through the extreme gradient boosting machine learning model. VwMS who smoke were matched with veterans without MS who smoke on factors including age, race, depression, and healthcare visits. To assess the marginal association of MS with different cessation treatments, we used logistic regression and conducted stratified analyses by sex, race, and ethnicity. The matched sample achieved a good balance across most covariates, compared to the pre-match sample. VwMS (n=3320) had decreased odds of receiving prescriptions for nicotine patches ([Odds Ratio]OR=0.86, p<.01), non-patch nicotine replacement therapy (NRT; OR=0.81, p<.001), and standard practice dual NRT (OR=0.77, p<.01), compared to matches without MS (n=13,280). Men with MS had lower odds of receiving prescriptions for nicotine patches (OR=0.88, p=.05), non-patch NRT (OR=0.77, p<.001), and dual NRT (OR=0.72, p<.001). Similarly, Black VwMS had lower odds of receiving prescriptions for patches (OR=0.62, p<.001), non-patch NRT (OR=0.75, p<.05), and dual NRT (OR=0.52, p<.01). The odds of receiving prescriptions for bupropion or varenicline did not differ between VwMS and matches without MS. VwMS received significantly less smoking cessation treatment, compared to matched controls without MS, showing a critical gap in health services as VwMS are not receiving dual NRT as the standard of care. Prescription rates were especially lower for male and Black VwMS, suggesting that under-represented demographic groups outside of the white female category, most often considered as the "traditional MS" group, could be under-treated regarding smoking cessation support. This foundational work will help inform future work to promote equitable treatment and implementation of cessation interventions for people living with MS.

Nelotanserin, a selective 5-HT2A receptor inverse agonist, attenuates aspects of nicotine withdrawal but not reward in mice

Nicotine smoking contributes to many preventable disabilities, diseases and deaths. Targeting nicotine reward and withdrawal is a basis for the majority of smoking cessation pharmacotherapies. Due to the emergence of interest in 5-HT2A receptor modulators for numerous psychiatric disorders, we investigated the effect of nelotanserin, a 5-HT2A receptor inverse agonist, on nicotine reward and withdrawal in ICR mice. In nicotine-dependent mice, nelotanserin dose-dependently reduced somatic signs of nicotine withdrawal and thermal hyperalgesia as measured in the hot plate test. However, nelotanserin had no effect on anxiety-like behavior and failed to reduce nicotine reward as measured in the conditioned place preference test. Our results suggest that inverse agonism of the 5-HT2A receptor may be a feasible novel mechanism for smoking cessation by reducing both physical withdrawal and thermal hyperalgesia associated with nicotine abstinence but may require complementary pharmacotherapies targeting affective and reward-associated decrements to improve cessation outcomes.

Abstract 2154: Actívatexto:Feasibility and acceptability of a mobile intervention that promotes smoking cessation and physical activity among Latinos

Abstract The purpose of this study was to assess the feasibility and acceptability of a mobile intervention that promotes smoking cessation and physical activity among Latinos. Twenty Latino adults who smoked and did not meet recommended levels of physical activity were recruited using community-based recruitment strategies. Participants received Actívatexto, a theory-based, culturally accommodated, 12-week text messaging intervention (available in English and Spanish) that promotes both smoking cessation and physical activity. Actívatexto integrates four components: 1) a text messaging program that promotes both smoking cessation and physical activity, 2) a wearable device to monitor physical activity, 3) an online dashboard where the research team manages participants’ incoming and outgoing data from both the text messaging program and wearable devices, and 4) smoking cessation pharmacotherapy (i.e., nicotine replacement therapies). We assessed self-reported 7-day point prevalence smoking abstinence (not smoking any cigarettes in the past seven days) at Month 3, weekly minutes of moderate to vigorous physical activity (MVPA), pharmacotherapy adherence, self-efficacy, and satisfaction. At baseline, participants’ mean age was 47.3 years old (SD 16.0), 55% of participants were female, 80% had completed high school or lower educational level, and 60% indicated that Spanish was their language of preference. Most participants (75%) smoked 1-10 cigarettes daily, 35% smoked their first cigarette within five minutes after waking up, and 60% used menthol cigarettes. At Month 3, 14 participants (70%) self-reported 7-day point prevalence smoking abstinence (90% follow-up rate). Fitbit-assessed mean minutes of MVPA per week increased from 113 (SD 127; range 0-399) at Week 1 to 177 (SD 163; range 0-513) at Month 3, although the difference was not statistically significant (p=0.15). Sixteen participants (88.9%, 16/18) reported NRT use in the past 90 days. Mean scores of self-efficacy for smoking cessation increased from 31.2 (SD 10.6) at baseline to 47.8 (SD 13.0) at Month 3 (p&amp;lt;0.01). Mean scores of self-efficacy for physical activity increased from 12.3 (SD 3.9) at baseline to 14.6 (SD 4.4) at Month 3 (p=0.2). Most participants reported being satisfied or extremely satisfied with the intervention (88.9%, 16/18). In conclusion, Actívatexto resulted in a noteworthy cessation rate at Month 3 (70%), increased mean minutes of MVPA per week, produced high use of NRT, increased self-efficacy for smoking cessation and physical activity, and was well received by participants. Additional testing in a formal randomized clinical trial is warranted to assess the efficacy of the intervention. Citation Format: Daimarelys Lara, Edgar I. Alaniz-Cantu, Arlette Chávez-Iñiguez, Daniel Fuller, Scott McIntosh, Deborah J. Ossip, Ana Paula Cupertino, Francisco Cartujano-Barrera. Actívatexto:Feasibility and acceptability of a mobile intervention that promotes smoking cessation and physical activity among Latinos [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2154.

Efficacy of varenicline or bupropion and its association with nicotine metabolite ratio among smokers with COPD.

Nicotine metabolic ratio (NMR) has been associated with nicotine metabolism and smoking characteristics. However, there are few studies on the potential association between NMR and smoking cessation efficacy in smokers with chronic obstructive pulmonary disease (COPD) in China or elsewhere. This study was a stratified block randomized controlled trial for smoking cessation in Chinese smokers with COPD. NMR was used as a stratification factor; slow metabolizers were defined as those with NMR <0.31, and normal metabolizers as those with NMR ≥0.31. Participants were randomly assigned to the varenicline or bupropion group. Follow-up visits were conducted at 1, 2, 4, 6, 9, 12 and 24 weeks. Two hundred twenty-four participants were recruited and analysed from February 2019 to June 2022. In normal metabolizers, the 9-12 weeks continuous abstinence rate of varenicline (43.1%) was higher than in bupropion (23.5%) (OR = 2.47, 95% CI 1.05-5.78, p = 0.038). There was no significant difference in abstinence rates between treatment groups in slow metabolizers (54.1% vs. 45.9%, OR = 1.39, 95% CI 0.68-2.83, p = 0.366). For slow metabolizers, the total score of side effects in the varenicline group was significantly higher than the bupropion group (p = 0.048), while there was no significant difference in side effects between groups for normal metabolizers (p = 0.360). Varenicline showed better efficacy than bupropion in normal metabolizers, and bupropion showed equivalent efficacy in slow metabolizers with less side effects. According to our study, NMR provides a better justification for both scientific research and tailoring optimal pharmacotherapy for smoking cessation among smokers in COPD.

Patterns of Smoking Cessation Strategies and Perception of E-cigarette Harm Among Bladder Cancer Survivors1

BACKGROUND: Cigarette smoking is the leading preventable cause of bladder cancer (BC). Some proponents of e-cigarettes describe their use as a risk mitigation strategy despite potential carcinogen exposure and uncertain long-term risks. OBJECTIVE: We assessed smoking cessation strategies, including e-cigarette use, and harm perception among patients with BC. METHODS: We performed a cross-sectional study on a convenience sample of patients with BC at a single institution from August 2021 –October 2022. The survey instrument was sourced from the Cancer Patient Tobacco Use Questionnaire (C-TUQ) from the American Association for Cancer Research with standardized questions on tobacco use, cessation questions, and e-cigarette harm perceptions. RESULTS: Of the 104 surveyed BC patients (mean age: 72 years; 27% female; 55% with muscle-invasive disease), 20% were current smokers (median pack years: 40) and 51% were former smokers (median pack years: 20). A minority (9%) had quit smoking at the time of diagnosis. Pharmacotherapy for smoking cessation included nicotine patches (25%), gum (21%), lozenges (8%), e-cigarettes (8%), and Varenicline/Bupropion (4%). Notably, 43% of patients who continued to smoke expressed willingness to switch to e-cigarettes as a cessation aid. E-cigarette users (11%) more commonly perceived e-cigarettes as non-harmful compared to former (4%) and non-smokers (4%) (P = .048), though all groups regarded e-cigarettes as equally addictive as traditional cigarettes. CONCLUSIONS: Despite the prevalence of BC survivors who continue to smoke, a significant proportion perceive e-cigarettes as a viable and less harmful cessation aid. The infrequent use of FDA-approved pharmacotherapies underscores potential implementation gaps. These findings highlight the need for further research and targeted interventions in addressing smoking cessation among BC survivors.

Insomnia and parasomnia induced by validated smoking cessation pharmacotherapies and electronic cigarettes: a network meta-analysis.

We aim to assess the relationship between validated smoking cessation pharmacotherapies and electronic cigarettes (e-cigarettes) and insomnia and parasomnia using a systematic review and a network meta-analysis. A systematic search was performed until August 2022 in the following databases: PUBMED, COCHRANE, CLINICALTRIAL. Randomized controlled studies against placebo or validated therapeutic smoking cessation methods and e-cigarettes in adult smokers without unstable or psychiatric comorbidity were included. The primary outcome was the presence of "insomnia" and "parasomnia." A total of 1261 studies were selected. Thirty-seven studies were included in the quantitative analysis (34 for insomnia and 23 for parasomnia). The reported interventions were varenicline (23 studies), nicotine replacement therapy (NRT, 10 studies), bupropion (15 studies). No studies on e-cigarettes were included. Bayesian analyses found that insomnia and parasomnia are more frequent with smoking cessation therapies than placebo except for bupropion. Insomnia was less frequent with nicotine substitutes but more frequent with bupropion than the over pharmacotherapies. Parasomnia are less frequent with bupropion but more frequent with varenicline than the over pharmacotherapies. Validated smoking cessation pharmacotherapies can induce sleep disturbances with different degrees of frequency. Our network meta-analysis shows a more favorable profile of nicotine substitutes for insomnia and bupropion for parasomnia. It seems essential to systematize the assessment of sleep disturbances in the initiation of smoking cessation treatment. This could help professionals to personalize the choice of treatment according to sleep parameters of each patient. Considering co-addictions, broadening the populations studied and standardizing the measurement are additional avenues for future research.

The Role of Twice-Daily N-acetylcysteine (NAC) 2400 mg in Smoking Cessation: A Randomized, Placebo-Controlled Trial in Indonesia.

Tobacco smoking remains a health concern, especially in developing countries. Nicotine is significantly linked to many cancers and even second-hand exposure. Hence, smoking can increase the risk of lung and heart disease.This makes quitting smoking important and challenging. Success tends to rise by achieving abstinence with assisted pharmacology. These treatments aim to reduce symptoms of nicotine withdrawal. This is a preclinical trial on glutamate modulator in N-acetylcysteine (NAC) as a new potential treatment for smoking cessation.It is based on the administration of NAC related to elevated levels of dopamine in the central nervous system to accomplish successful smoking cessation. This study evaluated the efficacy and tolerability of NAC for smoking cessation. The primary outcome was abstinence rate and the secondary outcomes of the study were to assess carbon monoxide exhalation value (COexh), the withdrawal symptoms, craving score, safety, and tolerability associated with the administration of NAC. This is a randomized clinical trial. Eligible smokers were treated with NAC 2400 mg twice daily (BID) or placebo to obtain a potential effective abstinence rate.Subjects recruited from the smoking cessation clinic were screened for eligibility and wererandomized to either the NAC or placebo group. The trial consisted of a four-week treatment phase and participants were evaluated each week with a brief counseling. Intention to treat data analysis was performed from 2018 to 2019. Smoking cessation status was verified by measuring the amount of carbon monoxide exhaled and by documenting their smoking habits.Adverse events (AEs) have also been observed on each visit. A total of 90male smokers with a mean (SD) age of 38.7 (11) years were randomized into two groups to receive NAC (n=45) and placebo (n=45). The primary outcome revealed that the abstinence rate was significantly higher for the NACgroup than the placebo group (37.7% vs 6.6%; p=0.02). These findings were supported by data comparison between the NAC group and placebo group of COexh (ppm)(9.59±7.4 vs 13,4±6.1; p=0.04) and cigarette consumption/week (10 vs 46; p <0.001), which were statistically significant. Comparison of withdrawal with the Minnesota Nicotine Withdrawal Score between theNACgroup and the placebo group showed lower values (8 (1-31) vs 11 (0-43); p=0.178), respectively, even though not statistically significant. Compared to the placebo group, the craving score (6 (2-29) vs 12 (6-31); p=0.04) in the NAC group was significantly lower. The most common adverse event was mild gastrointestinal effects (28.9%) and arthralgia (2.2%). No serious adverse events were detected. Despite a small sample size, the data demonstrate the potential benefits of NAC that may help elevate abstinence rates and promote successful smoking cessation pharmacotherapy. Comprehensive treatment combining pharmacologic therapy and counseling increases smoking cessation success rates. It is essential to conduct a randomized multicenter study with a large population to support a sustained abstinence rate using NAC.

Assessing the Impact of Smoking Cessation Interventions on Periodontal Health and Gingival Inflammation in Smokers with Periodontitis

ABSTRACT Background: Smoking is a well-established risk factor for periodontitis, a chronic inflammatory disease of the oral cavity. While smoking cessation has been linked to improved overall health, its specific impact on periodontal health and gingival inflammation in individuals with periodontitis remains less explored Materials and Methods: We conducted a prospective cohort study involving 200 smokers diagnosed with periodontitis. Participants were divided into two groups: Group A received comprehensive smoking cessation interventions, including counseling and pharmacotherapy, while group B continued smoking without intervention. Periodontal health was assessed through clinical parameters, including probing depth (PD) and clinical attachment level (CAL), at baseline and 6 months post intervention. Gingival inflammation was evaluated using the Gingival Index (GI). Results: After 6 months, group A exhibited a significant reduction in mean PD (from 4.5 mm to 3.2 mm) and CAL (from 5.0 mm to 3.5 mm) compared to group B. Conversely, group B showed no significant change in these parameters. The GI score significantly decreased in group A (from 2.8 to 1.2) but remained unchanged in group B. Furthermore, group A demonstrated a higher rate of smoking cessation (72%) compared to group B (14%) Conclusion: Smoking cessation interventions play a crucial role in improving periodontal health and reducing gingival inflammation in smokers with periodontitis. The observed reductions in PD, CAL, and gingival inflammation highlight the potential benefits of smoking cessation on oral health outcomes in this high-risk population.

Unrestricted public coverage is needed for smoking cessation pharmacotherapies.

Unrestricted public coverage is needed for smoking cessation pharmacotherapies.

Obstructive Sleep Apnea and Smoking Increase the Risk of Cardiovascular Disease: Smoking Cessation Pharmacotherapy.

Tobacco smoking has been a recognized risk factor for cardiovascular diseases (CVD). Smoking is a chronic relapsing disease and pharmacotherapy is a main component of smoking cessation. Obstructive sleep apnea (OSA) and smoking both increase the risk of CVD and are associated with significant morbidity and mortality. There are few existing data examining how pharmacological treatment, such as nicotine replacement therapy (NRT), bupropion, and varenicline, affect smokers suffering with OSA and especially their cardiovascular effects. The aim of this review was to evaluate the effects of smoking cessation pharmacotherapy on OSA with a special emphasis on the cardiovascular system. Results: Only small studies have assessed the effect of NRTs on OSA. Nicotine gum administration showed an improvement in respiratory events but with no permanent results. No specific studies were found on the effect of bupropion on OSA, and a limited number evaluated varenicline's effects on sleep and specifically OSA. Varenicline administration in smokers suffering from OSA reduced the obstructive respiratory events, especially during REM. Studies on second-line medication (nortriptyline, clonidine, cytisine) are even more limited. There are still no studies evaluating the cardiovascular effects of smoking cessation medications on OSA patients. Conclusions: Sleep disturbances are common withdrawal effects during smoking cessation but could be also attributed to pharmacotherapy. Smokers should receive personalized treatment during their quitting attempts according to their individual needs and problems, including OSA. Future studies are needed in order to evaluate the efficacy and safety of smoking cessation medications in OSA patients.

A smoking cessation intervention for rural veterans tailored to individual risk factors: A multicenter randomized clinical trial

IntroductionRates of cigarette use remain elevated among those living in rural areas. Depressive symptoms, risky alcohol use, and weight concerns frequently accompany cigarette smoking and may adversely affect quitting. Whether treatment for tobacco use that simultaneously addresses these issues affects cessation outcomes is uncertain. MethodsThe study was a multicenter, two-group, randomized controlled trial involving mostly rural veterans who smoke (N = 358) receiving treatment at one of five Veterans Affairs Medical Centers. The study randomly assigned participants to a tailored telephone counseling intervention or referral to their state tobacco quitline. Both groups received guideline-recommended smoking cessation pharmacotherapy, selected using a shared decision-making approach. The primary outcome was self-reported seven-day point prevalence abstinence (PPA) at three and six months. The study used salivary cotinine to verify self-reported quitting at six months. ResultsSelf-reported PPA was significantly greater in participants assigned to Tailored Counseling at three (OR = 1.66; 95 % CI: 1.07–2.58) but not six (OR = 1.35; 95 % CI: 0.85–2.15) months. Post hoc subgroup analyses examining treatment group differences based on whether participants had a positive screen for elevated depressive symptoms, risky alcohol use, and/or concerns about weight gain indicated that the cessation benefit of Tailored Counseling at three months was limited to those with ≥1 accompanying concern (OR = 2.02, 95 % CI: 1.20–3.42). Biochemical verification suggested low rates of misreporting. ConclusionsA tailored smoking cessation intervention addressing concomitant risk factors enhanced short-term abstinence but did not significantly improve long-term quitting. Extending the duration of treatment may be necessary to sustain treatment effects.

Early Treatment Response in Black Smokers Undergoing Pharmacotherapy for Smoking Cessation

This secondary analysis of a randomized clinical trial investigates the association of early treatment response with smoking cessation among Black smokers.

Abstract PO-058: Piloting a novel strategy to rapidly implement smoking cessation treatment for newly-diagnosed head and neck cancer patients

Abstract Purpose The purpose of this study is to evaluate a novel, bimodal strategy to implement smoking cessation treatment prior to oncologic therapy in newly-diagnosed head and neck cancer (HNC) patients. Background Among the 65,000 people who develop HNC in the United States (US) annually, 20-30% smoke cigarettes and 50-80% will continue smoking throughout survivorship. Quitting smoking before oncologic therapy correlates with improved health outcomes. However, the window of opportunity to quit smoking is narrow since cancer treatment often begins 4-5 weeks after the first oncology visit. The failure to rapidly implement evidence-based smoking cessation treatment is a major cause of this problem. Offering both behavioral therapy and pharmacotherapy increases abstinence rates by 2-3-fold. Despite this, only 4-17% of cancer patients receive both therapies at any time. Methods We conducted a pragmatic, quasi-experimental, pilot study using a pre-post design to evaluate a strategy to rapidly implement behavioral therapy and pharmacotherapy. The pre-test period was from 1/21-3/22 and the strategy was deployed from 4/22-10/22. The population included newly-diagnosed patients with mucosal HNC or salivary gland cancer. The setting was an academic medical center with an established tobacco treatment program (TTP). The implementation strategy involved bimodal administration of the evidence-based Ask, Advise, Connect (AAC) approach before and at the first surgical oncology visit. First, a dedicated medical assistant (MA) used an electronic health record (EHR)-based tool to identify, ask, advise, and connect (i.e. refer) smokers to the TTP at the time of clinic referral, or ~1-2 weeks before the first surgical oncology visit. Second, the AAC strategy was delivered by the triage MA and nurse at the time of the first surgical oncology visit. Some surgeons opportunistically offered patients pharmacotherapy. Results Among the 383 eligible, newly-diagnosed HNC patients, and 48 (12.5%) were current smokers. Twelve smokers were diagnosed between 4/22-10/22 and were eligible for the bimodal AAC strategy. However, only six of 12 patients received the AAC strategy before the first oncology visit. Among the 48 smokers, 75% were male, the median age was 65.5-years, and cancer treatment was started a median 34 days after the first oncology visit. Within 30 days of the first surgical oncology visit, 67% were advised to quit, 25% were referred to the TTP, 6% completed a comprehensive TTP visit, 21% had pharmacotherapy ordered, and 17% received both behavioral therapy and pharmacotherapy. While there were otherwise no differences in outcomes between pre- and post-strategy groups, more bimodal AAC strategy-eligible patients received pharmacotherapy (42%) compared to pre-strategy patients (14%, p=0.040). Conclusions Our bimodal AAC strategy correlated with increased use of pharmacotherapy, despite suboptimal fidelity to the approach. Additional strategies to improve delivery of timely behavioral therapy and pharmacotherapy for smoking cessation are needed. Citation Format: Sahajveer Mann, Julia Casazza, Dalia Mitchell, Quynh-Chi Dang, Dequan Weston, Brette Harding, Baran D. Sumer, Brittny Tillman, Heather Kitzman, George Jackson, Robert Schnoll, Amit Singal, Andrew T. Day. Piloting a novel strategy to rapidly implement smoking cessation treatment for newly-diagnosed head and neck cancer patients [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr PO-058.

Pharmacological and electronic cigarette interventions for smoking cessation in adults: component network meta-analyses.

Tobacco smoking is the leading preventable cause of death and disease worldwide. Stopping smoking can reduce this harm and many people would like to stop. There are a number of medicines licenced to help people quit globally, and e-cigarettes are used for this purpose in many countries. Typically treatments work by reducing cravings to smoke, thus aiding initial abstinence and preventing relapse. More information on comparative effects of these treatments is needed to inform treatment decisions and policies. To investigate the comparative benefits, harms and tolerability of different smoking cessation pharmacotherapies and e-cigarettes, when used to help people stop smoking tobacco. We identified studies from recent updates of Cochrane Reviews investigating our interventions of interest. We updated the searches for each review using the Cochrane Tobacco Addiction Group (TAG) specialised register to 29 April 2022. We included randomised controlled trials (RCTs), cluster-RCTs and factorial RCTs, which measured smoking cessation at six months or longer, recruited adults who smoked combustible cigarettes at enrolment (excluding pregnant people) and randomised them to approved pharmacotherapies and technologies used for smoking cessation worldwide (varenicline, cytisine, nortriptyline, bupropion, nicotine replacement therapy (NRT) and e-cigarettes) versus no pharmacological intervention, placebo (control) or another approved pharmacotherapy. Studies providing co-interventions (e.g. behavioural support) were eligible if the co-intervention was provided equally to study arms. We followed standard Cochrane methods for screening, data extraction and risk of bias (RoB) assessment (using the RoB 1 tool). Primary outcome measures were smoking cessation at six months or longer, and the number of people reporting serious adverse events (SAEs). We also measured withdrawals due to treatment. We used Bayesian component network meta-analyses (cNMA) to examine intervention type, delivery mode, dose, duration, timing in relation to quit day and tapering of nicotine dose, using odds ratios (OR) and 95% credibility intervals (CrIs). We calculated an effect estimate for combination NRT using an additive model. We evaluated the influence of population and study characteristics, provision of behavioural support and control arm rates using meta-regression. We evaluated certainty using GRADE. Of our 332 eligible RCTs, 319 (835 study arms, 157,179 participants) provided sufficient data to be included in our cNMA. Of these, we judged 51 to be at low risk of bias overall, 104 at high risk and 164 at unclear risk, and 118 reported pharmaceutical or e-cigarette/tobacco industry funding. Removing studies at high risk of bias did not change our interpretation of the results. Benefits We found high-certainty evidence that nicotine e-cigarettes (OR 2.37, 95% CrI 1.73 to 3.24; 16 RCTs, 3828 participants), varenicline (OR 2.33, 95% CrI 2.02 to 2.68; 67 RCTs, 16,430 participants) and cytisine (OR 2.21, 95% CrI 1.66 to 2.97; 7 RCTs, 3848 participants) were associated with higher quit rates than control. In absolute terms, this might lead to an additional eight (95% CrI 4 to 13), eight (95% CrI 6 to 10) and seven additional quitters per 100 (95% CrI 4 to 12), respectively. These interventions appeared to be more effective than the other interventions apart from combination NRT (patch and a fast-acting form of NRT), which had a lower point estimate (calculated additive effect) but overlapping 95% CrIs (OR 1.93, 95% CrI 1.61 to 2.34). There was also high-certainty evidence that nicotine patch alone (OR 1.37, 95% CrI 1.20 to 1.56; 105 RCTs, 37,319 participants), fast-acting NRT alone (OR 1.41, 95% CrI 1.29 to 1.55; 120 RCTs, 31,756 participants) and bupropion (OR 1.43, 95% CrI 1.26 to 1.62; 71 RCTs, 14,759 participants) were more effective than control, resulting in two (95% CrI 1 to 3), three (95% CrI 2 to 3) and three (95% CrI 2 to 4) additional quitters per 100 respectively. Nortriptyline is probably associated with higher quit rates than control (OR 1.35, 95% CrI 1.02 to 1.81; 10 RCTs, 1290 participants; moderate-certainty evidence), resulting in two (CrI 0 to 5) additional quitters per 100. Non-nicotine/placebo e-cigarettes (OR 1.16, 95% CrI 0.74 to 1.80; 8 RCTs, 1094 participants; low-certainty evidence), equating to one additional quitter (95% CrI -2 to 5), had point estimates favouring the intervention over control, but CrIs encompassed the potential for no difference and harm. There was low-certainty evidence that tapering the dose of NRT prior to stopping treatment may improve effectiveness; however, 95% CrIs also incorporated the null (OR 1.14, 95% CrI 1.00 to 1.29; 111 RCTs, 33,156 participants). This might lead to an additional one quitter per 100 (95% CrI 0 to 2). Harms There were insufficient data to include nortriptyline and non-nicotine EC in the final SAE model. Overall rates of SAEs for the remaining treatments were low (average 3%). Low-certainty evidence did not show a clear difference in the number of people reporting SAEs for nicotine e-cigarettes, varenicline, cytisine or NRT when compared to no pharmacotherapy/e-cigarettes or placebo. Bupropion may slightly increase rates of SAEs, although the CrI also incorporated no difference (moderate certainty). In absolute terms bupropion may cause one more person in 100 to experience an SAE (95% CrI 0 to 2). The most effective interventions were nicotine e-cigarettes, varenicline and cytisine (all high certainty), as well as combination NRT (additive effect, certainty not rated). There was also high-certainty evidence for the effectiveness of nicotine patch, fast-acting NRT and bupropion. Less certain evidence of benefit was present for nortriptyline (moderate certainty), non-nicotine e-cigarettes and tapering of nicotine dose (both low certainty). There was moderate-certainty evidence that bupropion may slightly increase the frequency of SAEs, although there was also the possibility of no increased risk. There was no clear evidence that any other tested interventions increased SAEs. Overall, SAE data were sparse with very low numbers of SAEs, and so further evidence may change our interpretation and certainty. Future studies should report SAEs to strengthen certainty in this outcome. More head-to-head comparisons of the most effective interventions are needed, as are tests of combinations of these. Future work should unify data from behavioural and pharmacological interventions to inform approaches to combined support for smoking cessation.

Integrated approach to pharmacotherapy in smoking cessation: the role of varenicline, bupropion, cytisine, and nicotine replacement therapy

Introduction: Smoking tobacco is a significant global health issue, contributing to various diseases, including heart disease, cancer, and respiratory disorders. Quitting smoking is not only a beneficial decision for an individual's health but also for society as a whole. Pharmacological therapy plays a crucial role in the smoking cessation process by supporting and increasing the chances of success. Aim: To compare four medications used in smoking cessation: varenicline, bupropion, cytisine, and nicotine replacement therapy, in terms of their characteristics, mechanism of action, efficacy, and adverse effects. Materials and Methods: A review of available data in the PubMed database regarding medications registered in Poland for the treatment of nicotine addiction. Key Results: The efficacy of all four medications in smoking cessation was demonstrated. Individuals using varenicline, bupropion, cytisine, or nicotine replacement therapy had higher chances of quitting smoking compared to placebo groups. Specifically, varenicline showed the highest efficacy among all the medications studied. Despite a high level of safety profile, each therapy can cause various adverse effects, with the most serious being the risk of seizures associated with bupropion. Conclusions: Varenicline, bupropion, cytisine, and nicotine replacement therapy are valuable tools in the process of smoking cessation and increase the chances of successfully quitting the addiction. The choice of a specific medication may depend on individual patient preferences and clinical factors. These findings should be taken into consideration when making therapeutic decisions in the field of smoking cessation.

Multiple Pharmacotherapy Adaptations for Smoking Cessation Based on Treatment Response in Black Adults Who Smoke

Adapting to different smoking cessation medications when an individual has not stopped smoking has shown promise, but efficacy has not been tested in racial and ethnic minority individuals who smoke and tend to have less success in quitting and bear a disproportionate share of tobacco-related morbidity and mortality. To evaluate efficacy of multiple smoking cessation pharmacotherapy adaptations based on treatment response in Black adults who smoke daily. This randomized clinical trial of adapted therapy (ADT) or enhanced usual care (UC) included non-Hispanic Black adults who smoke and was conducted from May 2019 to January 2022 at a federally qualified health center in Kansas City, Missouri. Data analysis took place from March 2022 to January 2023. Both groups received 18 weeks of pharmacotherapy with long-term follow-up through week 26. The ADT group consisted of 196 individuals who received a nicotine patch (NP) and up to 2 pharmacotherapy adaptations, with a first switch to varenicline at week 2 and, if needed, a second switch to bupropion plus NP (bupropion + NP) based on carbon monoxide (CO)-verified smoking status (CO ≥6 ppm) at week 6. The UC group consisted of 196 individuals who received NP throughout the duration of treatment. Anabasine-verified and anatabine-verified point-prevalence abstinence at week 12 (primary end point) and weeks 18 and 26 (secondary end points). The χ2 test was used to compare verified abstinence at week 12 (primary end point) and weeks 18 and 26 (secondary end points) between ADT and UC. A post hoc sensitivity analysis of smoking abstinence at week 12 was performed with multiple imputation using a monotone logistic regression with treatment and gender as covariates to impute the missing data. Among 392 participants who were enrolled (mean [SD] age, 53 [11.6] years; 224 [57%] female; 186 [47%] ≤ 100% federal poverty level; mean [SD] 13 [12.4] cigarettes per day), 324 (83%) completed the trial. Overall, 196 individuals were randomized to each study group. Using intent-to-treat and imputing missing data as participants who smoke, verified 7-day abstinence was not significantly different by treatment group at 12 weeks (ADT: 34 of 196 [17.4%]; UC: 23 of 196 [11.7%]; odds ratio [OR], 1.58; 95% CI, 0.89-2.80; P = .12), 18 weeks (ADT: 32 of 196 [16.3%]; UC: 31 of 196 [15.8%]; OR, 1.04; 95% CI, 0.61-1.78; P = .89), and 26 weeks (ADT: 24 of 196 [12.2%]; UC: 26 of 196 [13.3%]; OR, 0.91; 95% CI, 0.50-1.65; P = .76). Of the ADT participants who received pharmacotherapy adaptations (135/188 [71.8%]), 11 of 135 (8.1%) were abstinent at week 12. Controlling for treatment, individuals who responded to treatment and had CO-verified abstinence at week 2 had 4.6 times greater odds of being abstinent at week 12 (37 of 129 [28.7%] abstinence) than those who did not respond to treatment (19 of 245 [7.8%] abstinence; OR; 4.6; 95% CI, 2.5-8.6; P < .001). In this randomized clinical trial of adapted vs standard of care pharmacotherapy, adaptation to varenicline and/or bupropion + NP after failure of NP monotherapy did not significantly improve abstinence rates for Black adults who smoke relative to those who continued treatment with NP. Those who achieved abstinence in the first 2 weeks of the study were significantly more likely to achieve later abstinence, highlighting early treatment response as an important area for preemptive intervention. ClinicalTrials.gov Identifier: NCT03897439.

Smoking cessation pharmacotherapy use during index hospital admission following cystectomy for bladder cancer: A retrospective cohort study.

To identify gaps in urologic oncology quality and evidence-based smoking cessation care by assessing how often smoking cessation pharmacotherapy (SCP) is given in the inpatient setting following cystectomy. The Premier Healthcare Database (PHD), a deidentified all-payer dataset, was used to generate nationally representative estimates of SCP receipt during hospitalization following cystectomy for patients with bladder cancer who smoke. Regressions were used to model associations between SCP receipt and patient- and hospital-level factors. Of the 21,624 patients who underwent cystectomy for bladder cancer, 3,676 patients (17.0%) were identified as current smokers, representing a weighted estimate of 16,063 admissions. Among these admissions, 27.9% of patients received SCP, the vast majority of which (91.5%) received exclusively nicotine replacement therapy. Rates of SCP receipt varied substantially across hospitals (median: 25.0%, IQR: 20.0-33.3, range: 0.0-60.0). Older age and black race (aOR = 0.59, 95% CI: 0.42-0.82) were associated with lower odds of SCP receipt. Increased patient comorbidity score was associated with higher odds of SCP receipt (aOR = 1.02, 95% CI: 1.01-1.03); specifically, chronic pulmonary disease, alcohol abuse, and depression were independently associated with SCP receipt. Hospital teaching status, bed capacity, and mean annual cystectomy volume were not associated with SCP receipt. SCP receipt was not associated with hospital length of stay nor 90-day readmission or mortality following cystectomy. SCP is infrequently given to patients who smoke during their hospitalization following cystectomy for bladder cancer, representing a gap in quality urologic oncology care and a missed opportunity to effectively intervene with evidence-based treatment.

Effects of varenicline on the serum levels of olanzapine in male patients with Schizophrenia: a randomized controlled trial.

Smoking in patients with Schizophrenia is more common than in the general population. Varenicline, a partial agonist at α4β2 nicotinic acetylcholine receptors, is an effective smoking cessation pharmacotherapy in patients with Schizophrenia. However, its effects on the serum levels of antipsychotics in Schizophrenia are understudied. This study investigated the impact of smoking cessation with varenicline on the serum concentration of olanzapine in patients with Schizophrenia. Adult smokers with Schizophrenia were enrolled in a 12-week course of varenicline and placebo for smoking cessation. The serum concentration of olanzapine was measured at baseline and weeks 1, 2, 4, 8, and 12. Data were analyzed with the generalized additive mixed model. During the 12-week study, the results indicated that olanzapine concentrations increased nonlinearly in the varenicline and placebo groups. Threshold effect analysis suggested that the olanzapine concentrations increased over time until the turning point (week 4). However, there was no significant difference between the two treatment groups. Varenicline showed safety and efficacy in smoking cessation in people with Schizophrenia.

Prevalence and predictors of smoking cessation among smokers receiving smoking cessation intervention in primary care in Qatar: a 6-month follow-up study.

To estimate the rate and predictors of smoking cessation in smokers attending smoking cessation clinics in primary care settings in Qatar. A cross-sectional study was conducted among 759 smokers who had attended any of the 10 smoking cessation clinics in primary health care centers from January 2019 to June 2020. The sociodemographic, clinical, and smoking-related variables were assessed. Tailored behavioral and pharmacotherapy were delivered, and patients were interviewed at 6 months to estimate the 30-day point prevalence abstinence. To identify independent factors associated with smoking cessation, a multivariable logistic regression analysis was performed. The mean age of participants was 40.6 (±11.3), majority being married, Arab and employed, and having a tertiary education. Almost half of the smokers (48.7%) received varenicline alone, 42.6% received NRT, and 31.8% received a combination of both. The selection of drug therapy was based on preferences, experiences, and history of previously encountered adverse effects. The overall 30-day quit rate at 6 months follow-up was 32.4%. About three-quarters (72.5%) of participants had at least one quit attempt and 12.5% had 3 or more attempts. Later age at smoking initiation, lower cigarette consumption at baseline, lower CO concentration at baseline, use of smoking cessation pharmacotherapy, having made fewer quit attempts and non-exposure to secondhand smoke among friends were identified as significant predictors of successful quitting at 6 months. The 30-day quit rate at 6 months follow-up (32.4%) is comparable to the worldwide figure. However, further efforts should be made to plan cost-effective tobacco dependence treatment taking into account predictors and at-risk groups.

Promoting Evidence-Based Tobacco Cessation Treatment in Community Mental Health Clinics: Protocol for a Prepost Intervention Study.

Tobacco smoking is highly prevalent among persons with serious mental illness (SMI) and is the largest contributor to premature mortality in this population. Evidence-based smoking cessation therapy with medications and behavioral counseling is effective for persons with SMI, but few receive this treatment. Mental health providers have extensive experience working with clients with SMI and frequent treatment contacts, making them well positioned to deliver smoking cessation treatment. However, few mental health providers feel adequately trained to deliver this treatment, and many providers believe that smokers with SMI are not interested in quitting or have concerns about the safety of smoking cessation pharmacotherapy, despite substantial evidence to the contrary. We present the protocol for the pilot "IMPACT" (Implementing Action for Tobacco Smoking Cessation Treatment) study, which aims to pilot test a multicomponent implementation intervention to increase the delivery of evidence-based tobacco smoking cessation treatment in community mental health clinics. We are using a prepost observational design to examine the effects of an implementation intervention designed to improve mental health providers' delivery of the following four evidence-based practices related to smoking cessation treatment: (1) assessment of smoking status, (2) assessment of willingness to quit, (3) behavioral counseling, and (4) pharmacotherapy prescribing. To overcome key barriers related to providers' knowledge and self-efficacy of smoking cessation treatment, the study will leverage implementation strategies including (1) real-time and web-based training for mental health providers about evidence-based smoking cessation treatment and motivational interviewing, including an avatar practice module; (2) a tobacco smoking treatment protocol; (3) expert consultation; (4) coaching; and (5) organizational strategy meetings. We will use surveys and in-depth interviews to assess the implementation intervention's effects on providers' knowledge and self-efficacy, the mechanisms of change targeted by the intervention, as well as providers' perceptions of the acceptability, appropriateness, and feasibility of both the evidence-based practices and implementation strategies. We will use data on care delivery to assess providers' implementation of evidence-based smoking cessation practices. The IMPACT study is being conducted at 5 clinic sites. More than 50 providers have been enrolled, exceeding our recruitment target. The study is ongoing. In order for persons with SMI to realize the benefits of smoking cessation treatment, it is important for clinicians to implement evidence-based practices successfully. This pilot study will result in a set of training modules, implementation tools, and resources for clinicians working in community mental health clinics to address tobacco smoking with their clients. Trial Registration:ClinicalTrials.gov NCT04796961; https://clinicaltrials.gov/ct2/show/NCT04796961. ClinicalTrials.gov NCT04796961; https://clinicaltrials.gov/ct2/show/NCT04796961. DERR1-10.2196/44787.