Use Of Varenicline Research Articles

Varenicline: Efficacy, Precaution, and Safety in Smoking Cessation

Varenicline is a medication used to help people quit smoking when used in conjunction with education and counseling. It is the first-line treatment for smoking cessation and is available in 0.5 mg and 1 mg strength oral tablets. Varenicline is primarily eliminated via the kidney through glomerular filtration, and its excretion is via the renal route, so it is important to monitor renal function before and during treatment. Varenicline has been associated with an increased risk of new psychiatric conditions, anxiety, and mood disorders in some individuals. The use of Varenicline should be accompanied by close monitoring and careful consideration of individual patient factors. While Varenicline can be used in a wide range of patients, its use should be carefully considered in patients with heart or blood vessel disease, renal impairment, psychiatric disorder, or seizure.

8168 From Salt to the Sella- Discovering Empty Sella Syndrome as a Rare Cause of Severe Hyponatremia

Abstract Disclosure: P. Vemparala: None. S. Challagulla: None. Introduction: Hyponatremia is a common electrolyte disorder with potentially life-threatening consequences. Careful evaluation of hyponatremia can uncover significant underlying conditions. We present an interesting case of a patient who presented with symptoms of severe hyponatremia and a workup led us to the discovery of empty sella syndrome as the etiology. Case Presentation: A 54-year-old male with hypertension presented with 2 days of left-sided headache, blurred vision, generalized weakness, and vomiting. Pertinent medication history revealed the use of thiazide diuretic, bupropion and varenicline. Physical examination was unremarkable. Laboratory data showed severe hyponatremia with a serum sodium of 118 meq/L. Initial improvement with fluids was followed by a decline (106-112 meq/L). CT head without contrast showed a prominent empty sella turcica. Workup revealed urine osmolality and elevated urine sodium. A low AM cortisol level of 1.0 mcg/dl (reference range- AM- 7.0 - 25.0 mcg/dl), and decreased adrenocorticotropic hormone (ACTH) level of 5.2 pg/ml (reference range- 7.2 - 63.3 pg/ml) suggested secondary adrenal insufficiency. All other anterior pituitary hormones were normal. Brain magnetic resonance imaging (MRI) confirmed the diagnosis of partial empty sella. Treatment with hypertonic saline, fluid restriction, and steroids led to symptom resolution. Conclusion: Empty sella syndrome is a rare pituitary condition that can be primary- characterized by herniation of the subarachnoid space within the sella, or secondary- which occurs when the sella is empty due to damage to the pituitary gland by tumor, radiation, etc. It can cause potential hypopituitarism, be asymptomatic, or present with symptoms of raised intracranial pressure. In patients with hypopituitarism, deficiencies of ACTH and TSH are rarer and appear to be more common with a complete empty sella. This case emphasizes the need for a comprehensive hyponatremia workup, awareness of secondary adrenal insufficiency, and recognition of the life-threatening potential of even partial empty sella syndrome when untreated. Presentation: 6/1/2024

Effectiveness of smoking cessation interventions among adults: an overview of systematic reviews

BackgroundThis overview of reviews aims to identify evidence on the benefits (i.e. tobacco use abstinence and reduction in smoking frequency) and harms (i.e. possible adverse events/outcomes) of smoking cessation interventions among adults aged 18 years and older.MethodsWe searched Medline, Embase, PsycINFO, Cochrane Database of Systematic Reviews, Database of s of Reviews of Effects, the CADTH Health Technology Assessment Database and several other websites for grey literature. Searches were conducted on November 12, 2018, updated on September 24, 2020, with publication years 2008 to 2020. Two reviewers independently performed title-abstract and full-text screening considering pre-determined inclusion criteria. Data extraction and quality assessments were initially completed by two reviewers independently (i.e. 73% of included studies (n = 22)) using A Measurement Tool to Assess Systematic Reviews-2 (AMSTAR 2), and the remainder done by one reviewer and verified by another due to resources and feasibility. The application of Grading of Recommendations Assessment, Development and Evaluation (GRADE) was performed by one independent reviewer and verified by another.ResultsA total of 22 Cochrane systematic reviews evaluating the impact of smoking cessation interventions on outcomes such as tobacco use abstinence, reduction in smoking frequency, quality of life and possible adverse events were included. Pharmaceutical (i.e. varenicline, cytisine, nicotine replacement therapy (NRT), bupropion) and behavioural interventions (i.e. physician advice, non-tailored print-based self-help materials, stage-based individual counselling, etc.) showed to have increased smoking cessation; whereas, data for mobile phone-based interventions including text messaging, hypnotherapy, acupuncture, continuous auricular stimulation, laser therapy, electrostimulation, acupressure, St John’s wort, S-adenosyl-L-methionine (SAMe), interactive voice response systems and other combination treatments were unclear. Considering harms related to smoking cessation interventions, small/mild harms (i.e. increased palpitations, chest pain, nausea, insomnia, headache) were observed following NRT, varenicline and cytisine use. There were no data on harms related to behavioural therapies (i.e. individual or group counselling self-help materials, internet interventions), combination therapies or other therapies (i.e. laser therapy, electrostimulation, acupressure, St John’s wort, SAMe).ConclusionResults suggest that pharmacological and behavioural interventions may help the general smoking population quit smoking with observed small/mild harms following NRT or varenicline. Consequently, evidence regarding ideal intervention strategies and the long-term impact of these interventions for preventing smoking was unclear.Systematic review registrationPROSPERO CRD42018099691

A Pilot Study to Evaluate the Use of Automated Nicotine Metabolite Ratio Reporting Within Primary Care as an Implementation Strategy to Increase the Use of Tobacco Treatments.

Concerns about safety and effectiveness of tobacco treatments reduce their use. We explored integrating the nicotine metabolite ratio (NMR), and messaging about its potential for improving safety and effectiveness, as a strategy to increase the use of tobacco treatments within primary care. Through a prospective cohort design, we explored the effects of integrating NMR testing within primary care on the provision of tobacco treatment; 65 patients completed assessments including NMR before a clinic visit. At the clinic visit, patients' clinicians received an electronic health record (EHR) alert about the patient's NMR and personalized treatment recommendations to improve effectiveness and safety. Being asked about smoking and advised to quit, and a referral for tobacco treatment or medication prescription, were assessed within 30 days of the appointment and were compared to a usual care cohort (N = 85). The NMR and usual care cohorts reported similar rates of being asked about smoking (92.3% vs. 92.9%, p = 1.0), being advised to quit (72.3% vs. 74.1%, p = .85), being referred for tobacco treatment (23.1% vs. 36.5%, p = .11), and receiving tobacco use medications (20% vs. 27.1%, p = .34). In the NMR cohort, fast versus slow metabolizers were more likely to receive medication (26% vs. 0%, p = .003) and all patients who received varenicline (n = 8) were fast metabolizers. NMR results and treatment recommendations did not increase tobacco treatment rates in primary care, although it may increase treatment rates and the use of varenicline for fast metabolizers. Future studies could test ways to use the NMR to increase tobacco treatment rates in clinical settings. This study generated a novel implementation strategy, namely an EHR alert about patients' NMR and personalized treatment recommendations, in an effort to increase tobacco treatment rates in primary care. While the strategy did not increase tobacco treatment rates, it may have boosted the rate of varenicline prescription for patients who metabolize nicotine faster, aligning with evidence-based practice.

Impact of the disruption in supply of varenicline since 2021 on smoking cessation in England: A population study.

Varenicline is one of the most effective smoking cessation treatments. Its supply in England was disrupted in July 2021 due to nitrosamine impurities found by its supplier, Pfizer. This study measured the impact of this disruption on smoking cessation in England. The study used repeated cross-sectional surveys conducted monthly, from June 2018 to December 2022. Set in England, it comprised a total of 3024 adults who reported smoking during the past year and had made at least one serious attempt to quit in the past 6months. Generalized additive models analyzed the association of the varenicline supply disruption with the trend in self-reported varenicline use in the most recent quit attempt. We used these results to estimate the population-level impact of the disruption on smoking cessation. Before July 2021, the proportion of past 6-month quit attempts using varenicline was stable at approximately 3.9% [risk ratio (RR)trend = 1.034, 95% confidence interval (CI) = 0.823-1.298]. The trend in varenicline use has changed sharply since the supply disruption (RRΔtrend = 0.297, 95% CI = 0.120-0.738), with prevalence falling by 69.3% per year since; from 4.1% in June 2021 to 0.8% in December 2022. Convergently, National Health Service general practitioner prescribing data reported that just 0.1% of prescriptions for smoking cessation treatments in December 2022 were for varenicline. Assuming that varenicline does not return to the market, we estimate that this could result in ~8400 fewer people stopping smoking for at least 6months, ~4200 fewer long-term ex-smokers and ~1890 more avoidable deaths each year. In England, the disruption in supply of varenicline since 2021 has coincided with a substantial fall in the use of varenicline in attempts to quit smoking.

Economic Evaluation of Enhanced vs Standard Varenicline Treatment for Tobacco Cessation

Smoking is the leading preventable cause of death and illness in the US. Identifying cost-effective smoking cessation treatment may increase the likelihood that health systems deliver such treatment to their patients who smoke. To evaluate the cost-effectiveness of standard vs enhanced varenicline use (extended varenicline treatment or varenicline in combination with nicotine replacement therapy) among individuals trying to quit smoking. This economic evaluation assesses the Quitting Using Intensive Treatments Study (QUITS), which randomized 1251 study participants who smoked into 4 conditions: (1) 12-week varenicline monotherapy (n = 315); (2) 24-week varenicline monotherapy (n = 311); (3) 12-week varenicline combination treatment with nicotine replacement therapy patch (n = 314); or (4) 24-week varenicline combination treatment with nicotine replacement therapy patch (n = 311). Study enrollment occurred in Madison and Milwaukee, Wisconsin, between November 11, 2017, and July 2, 2020. Statistical analysis took place from May to October 2023. The primary outcome was 7-day point prevalence abstinence (biochemically confirmed with exhaled carbon monoxide level ≤5 ppm) at 52 weeks. The incremental cost-effectiveness ratio (ICER), or cost per additional person who quit smoking, was calculated using decision tree analysis based on abstinence and cost for each arm of the trial. Of the 1251 participants, mean (SD) age was 49.1 (11.9) years, 675 (54.0%) were women, and 881 (70.4%) completed the 52-week follow-up. Tobacco cessation at 52 weeks was 25.1% (79 of 315) for 12-week monotherapy, 24.4% (76 of 311) for 24-week monotherapy, 23.6% (74 of 314) for 12-week combination therapy, and 25.1% (78 of 311) for 24-week combination therapy, respectively. The total mean (SD) cost was $1175 ($365) for 12-week monotherapy, $1374 ($412) for 12-week combination therapy, $2022 ($813) for 24-week monotherapy, and $2118 ($1058) for 24-week combination therapy. The ICER for 12-week varenicline monotherapy was $4681 per individual who quit smoking and $4579 per quality-adjusted life-year (QALY) added. The ICER for 24-week varenicline combination therapy relative to 12-week monotherapy was $92 000 000 per additional individual who quit smoking and $90 000 000 (95% CI, $15 703 to dominated or more costly and less efficacious) per additional QALY. This economic evaluation of standard vs enhanced varenicline treatment for smoking cessation suggests that 12-week varenicline monotherapy was the most cost-effective treatment option at the commonly cited threshold of $100 000/QALY. This study provides patients, health care professionals, and other stakeholders with increased understanding of the health and economic impact of more intensive varenicline treatment options.

Trends in varenicline use for tobacco cessation, and their implications

BackgroundTobacco use remains a leading cause of death in the U.S. Varenicline is a preferred medication for tobacco cessation, and a prior report in the literature showed its use fell dramatically after the voluntary recall of Chantix (brand) varenicline (name) in July 2021. ObjectivesWorking with data on prescriptions for varenicline and nicotine-replacement therapy (NRT), we studied use from 2018 to 2023 to determine if varenicline use had recovered or if there had been a compensatory increase in NRT use. MethodsData are yearly from state employees and their dependents who were ≥18 years of age and were health-insurance beneficiaries of the Washington Public Employees Benefits Board from July 2018 through June 2023. Data include numbers of tobacco users and numbers of prescriptions filled. ResultsThe 5-year prevalence of tobacco use among 224,816 beneficiaries was 4.6%. The percentage of tobacco users who filled a prescription for varenicline fell from highs of 9.5% and 9.6% in the 2018–2019 and 2019–2020 years to lows of 5.3% and 6.4% in the 2021–2022 and 2022–2023 years. For nicotine replacement therapy, prescriptions rose modestly over the 5 years, from 4.5% in 2018–2019% to 6.0% in 2022–2023. DiscussionVarenicline use dropped after the voluntary recall of Chantix by Pfizer in mid-2021 and has not returned to prerecall levels. ConclusionPharmacists and other clinicians should address this drop, in addition to addressing longer-term challenges to increasing varenicline use; these include the requirement for a prescription and the black-box warning by the Food and Drug Administration, rescinded in 2016.

Varenicline and Maltodextrin Combination: A Promising Approach for Reducing Nitrosamine Impurities in Solid Dosage Forms

This research article investigates the use of varenicline and maltodextrin combination to reduce the nitrosamine impurities in varenicline tablets, a medication used to treat nicotine addiction. Nitrosamines are carcinogenic compounds that have been found in varenicline, raising concerns about its safety. Drug excipient compatibility was initially performed with all possible excipients, including maltodextrin, to identify potential approaches for reducing nitrosamine impurities. The results showed that maltodextrin was more effective than other excipients in reducing nitrosamines in the drug product. This finding provided an indication for the use of maltodextrin as a potential solution to the nitrosamine problem in varenicline tablets. The study involved preparing varenicline-maltodextrin formulations and analyzing the formulations for nitrosamine impurities. The finished formulation was prepared by simple mixing of varenicline, maltodextrin, disintegrant, filler, lubricant, and compression using suitable tooling, followed by aqueous film coating. The formulated tablets were tested for assay, content uniformity, dissolution in release media, and multimedia, and the results were found to be satisfactory. The results showed that the varenicline-maltodextrin combination significantly reduced nitrosamine content, and all other parameters were satisfactory. In addition, the nitrosamine impurity levels were significantly reduced to less than 3 ppm after 30 days of storage at 50±2°C/75±5 % RH. Moreover, more than 85% of drug release was observed in all tested release media, meeting the predefined specifications for BCS-based biowaiver. These findings suggest that the use of varenicline and maltodextrin combination is a promising approach to improve the safety of varenicline.

Cost-effectiveness of pharmaceutical smoking cessation intervention in China primary cancer prevention

Objectives: To evaluate the cost-effectiveness of typical pharmaceutical smoking cessation intervention strategies in China in the context of primary cancer prevention. Methods: Markov cohort simulation models were established to simulate the burden of 12 smoking caused cancer, including lung cancer, oral cancer, nasopharyngeal cancer, laryngeal cancer, esophageal cancer, gastric cancer, pancreatic cancer, liver cancer, kidney cancer, bladder cancer, cervical cancer, and acute myeloid leukemia. Taking incremental cost effectiveness ratio (ICER) as the main indicator, the model sets one year as the cycling period for 50 periods and simulates the cohort of 10 000 thirty-five-year-old current smokers with various smoking cessation strategies. To ensure the robustness of conclusion, univariate sensitivity analysis, probability sensitivity analysis, and age-group sensitivity analysis were conducted. Results: The results showed that varenicline intervention was the most cost-effective intervention. Compared to the next most effective option, incremental cost of each additional quality-adjusted life year is 11 140.28 yuan, which is below the threshold of willingness to pay (1 year GDP per capita). The value of ICER increased as the increasing age group of adopting intervention, but neither exceeded the threshold of willingness to pay. One-way sensitivity analysis showed that the value of discount rate, the hazard ratio and cost of intervention strategy had a greater impact on the result of ICER. Conclusion: In China, the use of varenicline to quit smoking is highly cost effective in the context of cancer primary prevention, especially for younger smokers.

Varenicline for smoking cessation in individuals who smoke cigarettes and use electronic cigarettes: a double-blind, randomised, placebo-controlled phase 3 trial

The efficacy and safety of varenicline for smoking cessation among individuals who smoke tobacco cigarettes and also use electronic cigarettes (known e-cigarettes or vapes) have not been studied. We aimed to address this knowledge gap and examine predictors for smoking abstinence. In this double-blind, placebo-controlled, single-centre randomised trial in Italy, we enrolled adults who had used an e-cigarette daily for at least 12 months and who also smoked at least one tobacco cigarette per day and had a willingness to quit smoking. 155 participants were randomly assigned to receive either varenicline (n=78) or matched placebo (n=77). Varenicline (1mg, administered twice daily for 12 weeks) was given in combination with smoking cessation counseling in dual users with an intention to quit smoking. Participants in both treatment groups received the same smoking cessation counselling throughout the whole duration of the study. The trial consisted of a 12-week treatment phase followed by a 12-week follow-up. The primary efficacy endpoint was continuous abstinence rate (CAR) in weeks 4-12. Secondary efficacy endpoints were the CAR in weeks 4-24 and 7-day point prevalence of smoking abstinence at weeks 12 and 24. This study is registered in EUDRACT, 2016-000339-42. Between November 2018, and February 2020, 114 participants (61 in the varenicline group and 53 in the placebo group) completed the intervention phase at week 12 and 88 participants (52 in the varenicline group and 36 in the placebo group) completed the follow-up phase at week 24. CARs were significantly higher for the varenicline vs placebo at each time-point: 50.0% vs 16.9% (OR=4.9; 95% CI, 2.3-10.4; P<0.0001) between weeks 4 and 12; and 48.7% vs 14.3% (OR=5.7; 95% CI, 2.6-12.3; P<0.0001) between weeks 4 and 24. The 7-day point prevalence of smoking abstinence was also higher for the varenicline than placebo at each time point. Adverse events were rated as mild or moderate and rarely led to treatment discontinuation. Our findings indicate that inclusion of varenicline in a cessation programme for adults who smoke and use e-cigarettes with an intention to quit smoking could result in smoking abstinence without serious adverse events. In the absence of evidence from other smoking cessation methods, it could be useful to suggest the use of varenicline in cessation programmes specifically designed to help dual users stop smoking. Further research in larger and more generalisable populations is required to strengthen such a suggestion. Global Research Award for Nicotine Dependence, an independently reviewed competitive grants programmeme funded by Pfizer.

Seeing Through the Blind: Belief About Treatment Randomization and Smoking Cessation Outcome Among People With Current or Past Major Depressive Disorder Who Smoke in a Placebo-Controlled Trial of Varenicline.

Blinding participants to randomization is a cornerstone of science. However, participant beliefs about their allocation can influence outcomes. We examined blind integrity, the association between trial arm belief and cessation, and potential mechanisms linking treatment arm and treatment arm belief among people with major depressive disorder (MDD) who smoke receiving varenicline in a placebo-controlled trial. 175 participants were asked at the end of treatment (EOT) if they thought they received placebo, varenicline, or were not sure. We assessed the relationship between treatment arm belief and actual treatment allocation, examined the association between treatment arm belief and EOT cessation, and evaluated changes in craving, withdrawal, side effects, depression symptoms, and smoking reward as mediators through which treatment arm was believed. Treatment arm belief was significantly associated with actual arm assignment (χ2(2) = 13.0, p = .002). Participants in the varenicline arm were >3 times as likely to believe they were taking varenicline, versus "not sure" (RR = 3.05 [1.41-6.60], p = .005). Participants in the placebo arm were just as likely to believe they were taking placebo versus "not sure" (χ2[2] = 0.75, p = .69). Controlling for treatment arm, belief that one received varenicline was significantly associated with an increase in cessation rate (OR = 5.91 [2.06-16.92], p = .001). Change in the rewarding experience of smoking may mediate participant ability to discern getting varenicline (B = 0.077 [0.002-0.192], p < .05). Participants receiving varenicline can discern that they received varenicline and this belief is associated with higher cessation rates. Research is needed to continue to examine how participants correctly identify their allocation to varenicline. Data come from the trial NCT02378714. The present study adds to the sparse literature on blind integrity, particularly in the field of tobacco cessation. Randomized clinical trial participants can discern their assignment to varenicline, and believing that one received varenicline was associated with significantly higher cessation rates. Identifying treatment arm allocation may be associated with changes in the rewarding aspects of smoking that have been well documented with varenicline use. Masking allocation to varenicline is challenging. The effects of this medication in clinical trials may represent both pharmacological effects and participants' abilities to recognize that they are receiving the medication.

Varenicline Combined With Oral Nicotine Replacement Therapy and Smartphone-Based Medication Reminders for Smoking Cessation: Feasibility Randomized Controlled Trial.

Varenicline and oral nicotine replacement therapy (NRT) have each been shown to increase the likelihood of smoking cessation, but their combination has not been studied. In addition, smoking cessation medication adherence is often poor, thus, challenging the ability to evaluate medication efficacy. This study examined the effects of combined varenicline and oral NRT and smartphone medication reminders on pharmacotherapy adherence and smoking abstinence among adults enrolled in smoking cessation treatment. A 2×2 factorial design was used. Participants (N=34) were randomized to (1) varenicline + oral NRT (VAR+NRT) or varenicline alone (VAR) and (2) smartphone medication reminder messages (REM) or no reminder messages (NREM) over 13 weeks. Participants assigned to VAR+REM received varenicline reminder prompts, and those assigned to VAR+NRT+REM also received reminders to use oral NRT. The other 2 groups (VAR+NREM and VAR+NRT+NREM) did not receive medication reminders. Participants were not blinded to intervention groups. All participants received tobacco cessation counseling. Smartphone assessments of smoking as well as varenicline and NRT use (if applicable) were prompted daily through the first 12 weeks after a scheduled quit date. Descriptive statistics were generated to characterize the relations between medication and reminder group assignments with daily smoking, daily varenicline adherence, and daily quantity of oral NRT used. Participants completed follow-up assessments for 26 weeks after the quit date. Participants were predominantly White (71%), and half were female (50%). On average, participants were 54.2 (SD 9.4) years of age, they smoked an average of 19.0 (SD 9.0) cigarettes per day and had smoked for 34.6 (SD 12.7) years. Descriptively, participants assigned to VAR+NRT reported more days of smoking abstinence compared to VAR (29.3 vs 26.3 days). Participants assigned to REM reported more days of smoking abstinence than those assigned to NREM (40.5 vs 21.8 days). Participants assigned to REM were adherent to varenicline on more days compared to those assigned to NREM (58.6 vs 40.5 days), and participants assigned to VAR were adherent to varenicline on more days than those assigned to VAR + NRT (50.7 vs 43.3 days). In the subsample of participants assigned to VAR+NRT, participants assigned to REM reported more days where ≥5 pieces of NRT were used than NREM (14.0 vs 7.4 days). Average overall medication adherence (assessed via the Medication Adherence Questionnaire) showed the same pattern as the daily smartphone-based adherence assessments. Preliminary findings indicated that smoking cessation interventions may benefit from incorporating medication reminders and combining varenicline with oral NRT, though combining medications may be associated with poorer adherence. Further study is warranted. ClinicalTrials.gov NCT03722966; https://classic.clinicaltrials.gov/ct2/show/NCT03722966.

Anti-smoking drugs cytisine and varenicline reduce cardiac reperfusion injury in rat model of myocardial ischemia

Evidence to date indicates that activation of nicotinic acetylcholine receptors (nAChRs) can reduce cardiac injury from ischemia and subsequent reperfusion. The use of nAChR agonists in various animal models leads to a reduction in reperfusion injury. Earlier this effect was shown for the agonists of α7 nAChR subtype. In this work, we demonstrated the expression of mRNA encoding α4, α6 and β2 nAChR subunits in the left ventricle of rat heart. In a rat model of myocardial ischemia, we studied the effect of α4β2 nAChR agonists cytisine and varenicline, medicines used for the treatment of nicotine addiction, and found them to significantly reduce myocardium ischemia-reperfusion injury, varenicline manifesting a higher protection. Dihydro-β-erythroidine, antagonist of α4β2 nAChR, as well as methyllycaconitine, antagonist of α7 and α6β2-containing nAChR, prevented protective effect of varenicline. This together with the presence of α4, α6 and β2 subunit mRNA in the left ventricule of rat heart raises the possibility that the varenicline effect is mediated by α4β2 as well as by α7 and/or α6β2-containing receptors. Our results point to a new way for the use of cytisine and varenicline as cardioprotective agents.

Varenicline and counseling for vaping cessation: a double-blind, randomized, parallel-group, placebo-controlled trial

BackgroundVaping cessation is virtually unexplored. The efficacy and safety of varenicline for vaping cessation has not been studied and rigorous research is required to advance best practice and outcomes for people who use electronic cigarettes (EC) and want to quit. The objective is to evaluate the efficacy and safety of varenicline (1 mg BID, administered for 12 weeks, with follow-up to week 24) combined with vaping cessation counseling in exclusive daily EC users intending to quit vaping.MethodsDesign: Double-blind, randomized, parallel-group, placebo-controlled trial.Setting: The study took place at a University-run smoking cessation center.Participants: People who exclusively use ECs daily and intend to quit vaping.Intervention: A total of 140 subjects were randomized to either varenicline (1 mg, administered twice daily for 12 weeks) plus counseling or placebo treatment (administered twice daily, for 12 weeks) plus counseling. The trial consisted of a 12-week treatment phase followed by a 12-week follow-up, nontreatment phase.Main outcomes and measures: The primary efficacy endpoint of the study was biochemically validated continuous abstinence rate (CAR) at weeks 4 to 12. Secondary efficacy end points were CAR at weeks 4 to 24 and 7-day point prevalence of vaping abstinence at weeks 12 and 24.ResultsCAR was significantly higher for varenicline vs placebo at each interval: weeks 4–12, 40.0% and 20.0%, respectively (OR = 2.67, 95% CI = [1.25–5.68], P = 0.011); weeks 4–24, 34.3% for varenicline with counseling and 17.2% for placebo with counseling (OR = 2.52, 95% CI = [1.14–5.58], P = 0.0224). The 7-day point prevalence of vaping abstinence was also higher for the varenicline than placebo at each time point. Serious adverse events were infrequent in both groups and not treatment-related.ConclusionsThe findings of the present RCT indicate that inclusion of varenicline in a vaping cessation program for people who use electronic cigarettes and intending to quit may result in prolonged abstinence. These positive findings establish a benchmark of intervention effectiveness, may support the use of varenicline combined with counseling in vaping cessation programs, and may also help guiding future recommendations by health authorities and healthcare providers.Trial registrationThe study has been registered in EUDRACT with Trial registration ID: 2016-000339-42.

Nonsmoking after simultaneous alcohol abstinence and smoking cessation program was associated with better drinking status outcome in Japanese alcohol-dependent men: A prospective follow-up study.

Growing evidence suggests that intervention for smoking cessation enhances alcohol abstinence in treatment settings for alcohol dependence. However, research in this field is rare in Asians. We prospectively investigated the association of smoking status with drinking status using 9 surveys mailed during a 12-month period in 198 Japanese alcohol-dependent men (70 never/ex-smokers and 128 smokers) who admitted for the first time and completed a 3-month inpatient program for simultaneous alcohol abstinence and smoking cessation. Nonsmoking during the first month after discharge and at the end of follow-up was reported in 28.9% and 25.0% of the baseline smokers, respectively. Kaplan-Meier estimates showed that a 12-month alcohol abstinence and heavy-drinking-free status were more frequent among never/ex-smokers (45.1% and 59.8%, respectively) and baseline smokers who quit smoking during the first month after discharge (59.0% and 60.8%, respectively), compared with sustained smokers (30.0% and 41.2%, respectively). Among the baseline smokers, the multivariate odds ratio (95% confidence interval) for smoking cessation during the first month were 2.77 (1.01-7.61) for alcohol abstinence during the period and 2.50 (1.00-6.25) for use of varenicline, a smoking cessation agent, during the inpatient program. After adjusting for age, drinking profile, lifestyle, family history of heavy or problem drinking, lifetime episodes of other major psychiatric disorders, and medications at discharge, the multivariate hazard ratios (HRs) for drinking lapse were 0.57 (0.37-0.89) for the never/ex-smoking and 0.41 (0.23-0.75) for new smoking cessation groups, respectively, compared with sustained smoking, while the corresponding HRs for heavy-drinking lapse were 0.55 (0.33-0.90) and 0.47 (0.25-0.88), respectively. The HR for drinking lapse was 0.63 (0.42-0.95) for the nonsmoking group (vs. smoking) during the observation period, while the HR for heavy-drinking lapse was 0.58 (0.37-0.91) for the nonsmoking group (vs. smoking) during the observation period. Other significant variables that worsened drinking outcomes were higher daily alcohol intake prior to hospitalization, family history of heavy or problem drinking and psychiatric medications at discharge. Nonsmoking was associated with better outcomes on the drinking status of Japanese alcohol-dependent men, and a smoking cessation program may be recommended to be integrated into alcohol abstinence programs.

Comparative effect of varenicline and nicotine patches on preventing repeat cardiovascular events

ObjectiveTo determine the comparative effectiveness of postdischarge use of varenicline versus prescription nicotine replacement therapy (NRT) patches for the prevention of recurrent cardiovascular events and mortality and whether this association...

Varenicline induced auditory hallucinations in a young female with bipolar disorder: a case report

IntroductionCreating appropriate and sustainable treatment plans for patients with concurrent disorders presents a challenge to psychiatrists and addiction medicine specialists alike. Although varenicline has been found to be one of the most effective medications for smoking cessation and abstinence, caution is needed when starting patients on this medication. In this case, a young female provisionally diagnosed with bipolar I disorder was hospitalized for a manic episode in the context of substance abuse and medical noncompliance. She also endorsed a long history of smoking, alcohol, cocaine, cannabis and ketamine use. In addition to being stabilized for bipolar disorder, the patient was started on varenicline for smoking cessation on Day 14 of admission.ObjectivesThis case report highlights the potential risk of de-stabilization in a vulnerable youth with newly diagnosed bipolar I disorder and precarious social circumstances, in attempts to further concurrent approaches to psychiatric care.MethodsIn addition to qualitative observations, the main objective exam used to track patient progress through the duration of her hospitalization was the mental status exam (MSE). This is standard practice for psychiatric care and qualitatively assessed factors related to a patient’s behavioral and cognitive functioning. Important factors assessed for this patient include appearance and behavior, speech, affect and mood, thought form, thought content, perceptual abnormalities, insight and cognition.ResultsPerceptual abnormalities, including auditory hallucinations, were not recorded at admission and the patient’s symptoms of mania were resolving clinically on Day 18. Two days after starting varenicline, the patient developed auditory hallucinations, paranoia and referential beliefs. However, her insight was intact, and she had minimal thought-form disorganization. The patient also reported hearing auditory hallucinations of a derogatory nature, with her mood appearing more distressed during varenicline use. Symptoms were found to be resolved shortly after the discontinuation of varenicline on Day 18 and the patient appeared to be less distressed on following days. In this case, these symptoms were not in keeping with her bipolar diagnosis and thought to be secondary to varenicline after the consideration of potential alternative contributors.ConclusionsThe occurrence of side effects as a result of varenicline use in patients with diagnosed mental health conditions is rare and underlying psychiatric illness is not labeled as an absolute contraindication in the prescription of varenicline. However, it is important to advocate for increased guidance and research on the treatment of substance use disorders in patients with bipolar I disorder.Disclosure of InterestNone Declared

A pragmatic review of varenicline prescribing practices

BackgroundSmoking is the leading preventable cause of illness and premature death worldwide. Most tobacco users desire to quit, but few are successful. Guidelines recommend varenicline as an initial treatment recommendation to support smoking cessation. ObjectivesDetermine whether historic warnings preclude the use of varenicline as an initial treatment recommendation in patients with and without certain comorbidities. Appendix 1 shows the questions asked in the survey. MethodsThis study was conducted in 2 parts. Part 1 of this study was a provider survey. Part 2 was a multicenter, retrospective chart review. Survey respondents were primary care providers (PCPs) or internal medicine residents within a large health system. Patients included in the chart review had a PCP appointment between January 1, 2017, and December 31, 2020, and a diagnosis of tobacco dependence or tobacco cessation therapy prescription. ResultsIn total, 352 providers were included in survey distribution and 56 responses were received, resulting in a response rate of 16%. Most providers (77%) indicated that they would be likely to use varenicline as an initial treatment recommendation in a patient with no comorbidities. Providers indicated they would be unlikely to use varenicline in a patient with certain mental health comorbidities (43%, 43%, and 55% for patients with bipolar disorder, schizophrenia, or history of suicide attempts, respectively, with 25%, 30%, and 27% having no opinion for each group). In addition, chart review yielded data for 25,128 patients. Notably, patients with schizophrenia were found to have an odds ratio of 0.55 (95% confidence interval [CI] 0.39–0.77) to receive varenicline at any point in therapy, and patients with diabetes had an odds ratio of 2.66 (95% CI 2.22–3.19) to receive no treatment. ConclusionsHistoric warnings for neuropsychiatric events with varenicline may still preclude usage in patients with serious psychiatric comorbidities such as schizophrenia. In addition, patients with diabetes were less likely to receive any form of tobacco cessation therapy.

Varenicline induced auditory hallucinations in a young female with bipolar disorder: a case report

BackgroundCreating appropriate and sustainable treatment plans for patients with concurrent disorders presents a challenge to psychiatrists and addiction medicine specialists alike. Although varenicline has been found to be the most effective medication for smoking cessation and abstinence when compared to results from placebo medications, nicotine patches and bupropion, caution is needed when starting patients on this medication. With the high prevalence of concurrent mental health and substance use disorders in vulnerably-housed populations in Canada, it becomes increasingly important to advocate for increased guidance and research into treating concurrent disorders.Case presentationIn this case, a young female patient provisionally diagnosed with bipolar I disorder was hospitalized for a manic episode in the context of substance use and medication noncompliance. She also endorsed a long history of tobacco, alcohol, cocaine, cannabis and ketamine use. Perceptual abnormalities, including auditory hallucinations, were not recorded at admission. In addition to being stabilized for bipolar diagnosis, the patient was started on nicotine replacement therapy on Day 7 of admission followed by initiation of varenicline for smoking cessation on Day 14 of admission. Soon after the varenicline treatment was started, the patient developed auditory hallucinations, paranoia and referential beliefs. However, her insight was intact, and she had minimal thought form disorganization. In this case, these symptoms were thought to be secondary to varenicline after the consideration of potential alternative contributors.ConclusionThe occurrence of side effects as a result of varenicline use in patients with diagnosed mental health conditions is rare and underlying psychiatric illness is not labeled as an absolute contraindication in the prescription of varenicline. However, it is important to advocate for increased guidance and research on the treatment of substance use disorders in patients with bipolar I disorder. Patients may also benefit from increased collaboration between psychiatric and addiction services as that may allow for earlier recognition and intervention of symptoms to minimize distress.

Evaluation of Youtube content regarding Varenicline and smoking cessation

Introduction. The use of varenicline, an effective way to quit smoking, has become a subject of discussion in the mainstream media, social media, and the internet due to the growing number of people trying to quit smoking. YouTube videos serve a significant purpose in the drive towards smoking cessation with the aid of the drug mentioned above. This study aimed to evaluate the content of videos related to varenicline on YouTube.&#x0D; Material and methods. Six different research terms were created for a search on YouTube. Two reviewers evaluated the videos for quality, reliability, and usefulness. After detecting useful and misleading videos, the factors affecting them as video parameters in these groups were compared.&#x0D; Results. Of the videos evaluated, 78% were classified as useful, while the remaining 22% were misleading. Video length, number of likes and the likes ratio showed no significant difference between these two groups (p=0.264; p=0.075; p=0.798). The DISCERN (DS) and Global Quality Scale (GQS) scores of misleading videos were significantly lower (p=0.001). The DS and GQS scores of the useful videos were 2.58±1.11 and 2.67±1.05, respectively.&#x0D; Conclusions. Misleading videos had a higher number of views and comments compared to useful videos. It was observed that independent YouTube users and media sources are producing more misleading videos. It is very concerning that cigarette quitters do not develop awareness in decision making about the misleading information from media and independent users. In contrast, health pages, physicians, and patient experiences can guide those trying to stop smoking.