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Mayo Clinic Proceedings. Innovations,... Oct 2022To evaluate the safety and effectiveness of combination varenicline with lorcaserin in preventing post-cessation weight gain.
OBJECTIVE
To evaluate the safety and effectiveness of combination varenicline with lorcaserin in preventing post-cessation weight gain.
PARTICIPANTS AND METHODS
We conducted a randomized (varenicline for 12 weeks + lorcaserin for 24 weeks vs varenicline for 12 weeks + placebo for 24 weeks) phase II clinical study to obtain preliminary data on the safety and effectiveness of combination varenicline and lorcaserin in preventing post-cessation weight gain in overweight and obese smokers. Eighty-four overweight and obese (body mass index [BMI], 27-40 kg/m) cigarette smokers were randomized before study termination (lorcaserin: n=40; placebo: n=44). The primary outcomes were weight and waist circumference (WC) changes at 12 and 24 weeks in smokers meeting criteria for prolonged smoking abstinence.
RESULTS
Thirty-nine participants met criteria for prolonged smoking abstinence at 12 weeks (46%) and 21 at 24 weeks (25%). No significant treatment effect was observed at 12 weeks with lorcaserin compared with placebo (weight difference, -0.7 kg; 90% CI, -2.6 to 1.1 kg; =.51; WC difference, -1.9 cm; 90% CI, -4.2 to 0.5 cm; =.18; or BMI difference, -0.4 kg/m; 90% CI, -1.1 to 0.3 kg/m; =.33). No significant treatment effect was observed between lorcaserin at 24 weeks compared with placebo (weight, 1.4 kg; 90% CI, -3.8 to 6.7 kg; =.65; WC, -0.9 cm; 90% CI, -5.8 to 4.0 cm; =.75; or BMI 0.29 kg/m; 90% CI, -1.5 to 2.12 kg/m; =.79).
CONCLUSION
Weight gain and WC increases after prolonged smoking abstinence were not reduced using combination varenicline and lorcaserin. The results do not support further research in the obese and weight-concerned smoking population using lorcaserin or similar drugs.
TRIAL REGISTRATION
clinicaltrials.gov Identifier: NCT02412631.
PubMed: 36160639
DOI: 10.1016/j.mayocpiqo.2022.01.004 -
Federal Practitioner : For the Health... Jul 2022Pharmacists are uniquely positioned to provide tobacco cessation interventions given their medication expertise and accessibility to the public. The purpose of this...
BACKGROUND
Pharmacists are uniquely positioned to provide tobacco cessation interventions given their medication expertise and accessibility to the public. The purpose of this study was to evaluate the efficacy and safety of management of varenicline by clinical pharmacy specialists (CPSs) compared with other clinicians.
METHODS
This retrospective chart review included patients with a varenicline prescription between July 1, 2019, and July 31, 2020. Primary outcomes were reduction in tobacco use at 12 weeks from baseline, continuous abstinence at 12 weeks, adherence to varenicline therapy, and time to first follow-up. For safety evaluation, charts were reviewed for documented adverse drug reactions.
RESULTS
Management by CPS compared with other clinicians was associated with similar mean (SD) reductions of tobacco use (-7.9 [10.4] vs -5.4 [9.8] cigarettes per day, respectively; = .15) and rates of complete abstinence (34% vs 38%, respectively; = .73) and higher adherence (42% vs 31%, respectively; = .01). Mean (SD) time to first follow-up was shorter for patients in the CPS group: 52 (66) vs 163 (110) days; < .001. Adverse events were more common in the CPS group compared with the other clinicians group (42% vs 23%; = .02).
CONCLUSIONS
These results suggest that CPS management of varenicline is as safe and effective as management by other clinicians. Additional research is needed to fully characterize the impact of pharmacist management of varenicline, justify expansion of CPS scope of practice, and ultimately enhance patient outcomes regarding tobacco cessation.
PubMed: 36425350
DOI: 10.12788/fp.0290 -
Nicotine & Tobacco Research : Official... Jan 2023Waterpipe smoking is increasing worldwide with no proven interventions for cessation. We compared abstinence rates with 12-week varenicline therapy versus placebo among... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Waterpipe smoking is increasing worldwide with no proven interventions for cessation. We compared abstinence rates with 12-week varenicline therapy versus placebo among habitual waterpipe smokers willing to quit.
METHODS
This double-blind placebo-controlled single-center trial, randomized waterpipe smokers from Lebanon who did not smoke other tobacco products to receive varenicline or placebo for 12 weeks. All participants also received three structured 30-minute individual behavioral intervention sessions. The primary outcome was repeated point prevalence abstinence assessed by self-report and verified by exhaled carbon monoxide three times during 12 weeks and analyzed with the intention to treat. End of treatment urine cotinine, weight, blood pressure, anxiety, depression, withdrawal, and adverse symptoms were also assessed.
RESULTS
In total, 152 waterpipe smokers (mean age 38 years [SD = 13], 39% females) willing to quit, who smoked waterpipe exclusively (average 2.3 per day [SD = 1.6] for 16.8 years [SD = 10.8]) were randomized. Seventy-nine participants (52%) with any missing abstinence assessment were considered to have relapsed. Repeat point prevalence abstinence rate was numerically higher among the varenicline group compared to placebo, but the difference did not reach statistical significance when assessed by self-report (16.9 vs. 13.6%, respectively, p = .6) and when further verified by exhaled carbon monoxide (14.1% vs. 9.9%, respectively, p = .4). Abstinence rates were similar in both groups when further verified by urine cotinine at end of treatment. No serious adverse events were reported, adverse symptoms and other outcomes were similar in the varenicline and placebo arms.
CONCLUSIONS
Varenicline for 12 weeks was not more effective than placebo to achieve abstinence among daily waterpipe smokers.
IMPLICATIONS
Varenicline in combination with a behavioral intervention did not significantly enhance the quit rate among exclusive waterpipe smokers compared to behavioral intervention plus placebo. We experienced difficulty enrolling exclusive waterpipe smokers willing to quit and observed high dropout rates among participants demonstrating the difficulties of waterpipe smoking cessation.
Topics: Female; Humans; Adult; Male; Varenicline; Smoking Cessation; Water Pipe Smoking; Carbon Monoxide; Cotinine; Nicotinic Agonists
PubMed: 35789389
DOI: 10.1093/ntr/ntac162 -
Journal of Addiction MedicineVarenicline is a partial agonist at the α2β4 and α6β2 nAChR receptors and a full agonist at α7 receptors. Both α7 and α6β2 receptors are implicated in the neural...
OBJECTIVES
Varenicline is a partial agonist at the α2β4 and α6β2 nAChR receptors and a full agonist at α7 receptors. Both α7 and α6β2 receptors are implicated in the neural reward circuitry activated by cocaine use. A preliminary clinical trial suggested that varenicline treatment reduced cocaine use. This trial was intended to replicate and extend the findings of the previous trial.
METHODS
This was a 12-week, double-blind, placebo-controlled clinical trial involving 156 subjects with DSM IV cocaine dependence. Subjects received up to 2 mg of varenicline or identical placebo daily along with weekly relapse prevention psychotherapy. The primary outcome measure was cocaine use measured by thrice-weekly urine drug screens. Additional outcome measures included end of study cocaine abstinence, cocaine craving, cocaine withdrawal symptom severity, cigarette use, and global improvement measure by the Clinical Global Improvement Scale.
RESULTS
End of study cocaine abstinence, measured by urine drug screens during the last 3 weeks of the trial, was not different between groups (8% in the varenicline treated subjects and versus 9% in placebo-treated subjects). Generalized estimating equations analysis of urine drug screen results showed no significant difference between groups in cocaine abstinence over the 12 weeks of the trial. There were no significant differences between the 2 groups in cocaine craving or cocaine withdrawal symptom severity. Varenicline was well-tolerated. There were no medication-associated serious adverse events.
CONCLUSIONS
Varenicline plus cognitive-behavioral therapy does not seem to be an efficacious treatment for cocaine dependence.
Topics: Cocaine-Related Disorders; Double-Blind Method; Humans; Nicotinic Agonists; Treatment Outcome; Varenicline
PubMed: 33840773
DOI: 10.1097/ADM.0000000000000842 -
Frontiers in Pharmacology 2022Compounds known to be successful in the treatment of alcohol use disorder include the aversive agent, Disulfiram, the glutamatergic NMDA receptor antagonist,... (Review)
Review
Compounds known to be successful in the treatment of alcohol use disorder include the aversive agent, Disulfiram, the glutamatergic NMDA receptor antagonist, Acamprosate, and the opioid receptor antagonists, Naltrexone and Nalmefene. Although all four are effective in maintaining abstinence or reduction of alcohol consumption, only a small percentage of patients receive pharmacological treatment. In addition, many other medications have been investigated for their therapeutic potential in the treatment of alcohol use disorder. In this review we summarize and compare Baclofen, Gabapentin, Topiramate, Ondansetron, Varenicline, Aripiprazole, Quetiapine, Clozapine, Antidepressants, Lithium, Neuropeptide Y, Neuropeptide S, Corticotropin-releasing factor antagonists, Oxytocin, PF-05190457, Memantine, Ifenprodil, Samidorphan, Ondelopran, ABT-436, SSR149415, Mifepristone, Ibudilast, Citicoline, Rimonabant, Surinabant, AM4113 and Gamma-hydroxybutyrate While some have shown promising results in the treatment of alcohol use disorder, others have disappointed and should be excluded from further investigation. Here we discuss the most promising results and highlight medications that deserve further preclinical or clinical study. Effective, patient-tailored treatment will require greater understanding provided by many more preclinical and clinical studies.
PubMed: 36263121
DOI: 10.3389/fphar.2022.927703 -
Journal of the American Pharmacists... 2021Electronic cigarettes (e-cigarettes) have been touted as a safer alternative to cigarettes and even as a smoking cessation aid. The health risks associated with smoking...
Electronic cigarettes (e-cigarettes) have been touted as a safer alternative to cigarettes and even as a smoking cessation aid. The health risks associated with smoking are well known, and smoking cessation has been studied extensively with options including behavioral therapy and pharmacotherapy (nicotine replacement therapy [NRT], varenicline, and bupropion). Several studies analyzed the effects of e-cigarettes as a smoking cessation aid. When used for smoking cessation, those who successfully abstain from cigarette smoking have a higher rate of continuation on e-cigarettes than NRT or pharmacotherapy. Other risks of e-cigarettes are highlighted including e-cigarette or vaping product use-associated lung injury. There is no approved pharmacotherapy for e-cigarette cessation. Two of the analyzed studies demonstrated the use of varenicline as a potential pharmacotherapy for e-cigarette cessation. The proposed benefits of e-cigarettes as a smoking cessation aid should be weighed against their probable detrimental effects. E-cigarette use should be discouraged as a whole and notably, as a smoking cessation aid.
Topics: Electronic Nicotine Delivery Systems; Humans; Smoking; Smoking Cessation; Tobacco Use Cessation Devices
PubMed: 34034964
DOI: 10.1016/j.japh.2021.05.001 -
Psychological Medicine Oct 2019Accumulating evidence shows that a propensity towards a pro-inflammatory status in the brain plays an important role in schizophrenia. Anti-inflammatory drugs might... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Accumulating evidence shows that a propensity towards a pro-inflammatory status in the brain plays an important role in schizophrenia. Anti-inflammatory drugs might compensate this propensity. This study provides an update regarding the efficacy of agents with some anti-inflammatory actions for schizophrenia symptoms tested in randomized controlled trials (RCTs).
METHODS
PubMed, Embase, the National Institutes of Health website (http://www.clinicaltrials.gov), and the Cochrane Database of Systematic Reviews were systematically searched for RCTs that investigated clinical outcomes.
RESULTS
Our search yielded 56 studies that provided information on the efficacy of the following components on symptom severity: aspirin, bexarotene, celecoxib, davunetide, dextromethorphan, estrogens, fatty acids, melatonin, minocycline, N-acetylcysteine (NAC), pioglitazone, piracetam, pregnenolone, statins, varenicline, and withania somnifera extract. The results of aspirin [mean weighted effect size (ES): 0.30; n = 270; 95% CI (CI) 0.06-0.54], estrogens (ES: 0.78; n = 723; CI 0.36-1.19), minocycline (ES: 0.40; n = 946; CI 0.11-0.68), and NAC (ES: 1.00; n = 442; CI 0.60-1.41) were significant in meta-analysis of at least two studies. Subgroup analysis yielded larger positive effects for first-episode psychosis (FEP) or early-phase schizophrenia studies. Bexarotene, celecoxib, davunetide, dextromethorphan, fatty acids, pregnenolone, statins, and varenicline showed no significant effect.
CONCLUSIONS
Some, but not all agents with anti-inflammatory properties showed efficacy. Effective agents were aspirin, estrogens, minocycline, and NAC. We observed greater beneficial results on symptom severity in FEP or early-phase schizophrenia.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Humans; Schizophrenia
PubMed: 31439071
DOI: 10.1017/S0033291719001995 -
Nicotine & Tobacco Research : Official... Aug 2023A smoking-cessation program was implemented as a randomized non-inferiority trial in primary care practices in Croatia and Slovenia to investigate whether a standard... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
A smoking-cessation program was implemented as a randomized non-inferiority trial in primary care practices in Croatia and Slovenia to investigate whether a standard 4-week treatment with cytisine was at least as effective and feasible as a standard 12-week treatment with varenicline in helping smokers quit.
AIMS AND METHODS
Out of 982 surveyed smokers, 377 were recruited to the non-inferiority trial: 186 were randomly assigned to cytisine and 191 to varenicline treatment. The primary cessation outcome was 7-day abstinence after 24 weeks, while the primary feasibility outcome was defined by adherence to the treatment plan. We also compared the rates of adverse events between the two treatment groups.
RESULTS
The cessation rate after 24 weeks was 32.46% (62/191) in the varenicline group and 23.12% (43/186) in the cytisine group (odds ratio [OR]: 95%, credible interval [CI]: 0.39 to 0.98). Of 191 participants assigned to varenicline treatment 59.16% (113) were adherent, while 70.43% (131 of 186) were adherent in the cytisine group (OR: 1.65, 95% CI: 1.07 to 2.56). Participants assigned to cytisine experienced fewer total (incidence rate ratio [IRR]: 0.59, 95% CI: 0.43 to 0.81) and fewer severe or more extreme adverse events (IRR: 0.72, 95% CI: 0.35 to 1.47).
CONCLUSIONS
This randomized non-inferiority trial (n = 377) found the standard 4-week cytisine treatment to be less effective than the standard 12-week varenicline treatment for smoking cessation. However, adherence to the treatment plan, ie, feasibility, was higher, and the rate of adverse events was lower among participants assigned to cytisine treatment.
IMPLICATIONS
The present study found the standard 12 weeks of varenicline treatment to be more effective than the standard 4 weeks of cytisine treatment for smoking cessation in a primary care setting in Croatia and Slovenia. Participants assigned to cytisine, however, had a higher adherence to the treatment plan and a lower rate of adverse events. Estimates from the present study may be especially suitable for generalizations to high-smoking prevalence populations in Europe. Given the much lower cost of cytisine treatment, its lower rate of adverse events, and higher feasibility (but its likely lower effectiveness with the standard dosage regimen), future analyses should assess the cost-effectiveness of the two treatments for health policy considerations.
Topics: Humans; Alkaloids; Azocines; Benzazepines; Nicotine; Nicotinic Agonists; Primary Health Care; Quinolizines; Smoking Cessation; Treatment Outcome; Varenicline
PubMed: 37291049
DOI: 10.1093/ntr/ntad065 -
The Medical Letter on Drugs and... Jul 2019
Review
Topics: Bupropion; Humans; Randomized Controlled Trials as Topic; Smoking Cessation; Smoking Cessation Agents; Tobacco Use Cessation Devices; Varenicline
PubMed: 31381546
DOI: No ID Found -
Journal of Comparative Effectiveness... Jun 2023Herein, we report safety outcomes for varenicline solution nasal spray (VNS) within the context of clinical trial discontinuation, contrasting those with... (Randomized Controlled Trial)
Randomized Controlled Trial
Herein, we report safety outcomes for varenicline solution nasal spray (VNS) within the context of clinical trial discontinuation, contrasting those with discontinuation outcomes from topical cyclosporine and lifitegrast clinical trials. 1061 subjects were randomized across three clinical trials to receive either VNS 0.06 mg, VNS 0.03 mg, VNS 0.006 mg or vehicle control. Subjects who discontinued from treatment were noted and assigned to their appropriate categories. Despite treatment emergent adverse events, 93.5% of subjects receiving VNS completed the treatment period. By comparison, only 80% of subjects in the integrated clinical trials for cyclosporine ophthalmic emulsion and 91% of subjects in the integrated trials for lifitegrast ophthalmic solution completed the full treatment period, respectively. In clinical trials, VNS demonstrated improvements in dry eye disease signs and symptoms, was well-tolerated, and had an overall completion rate >93%. Conventional dry eye treatments (e.g., cyclosporine and lifitegrast) noted considerably higher discontinuation rates in their clinical trials.
Topics: Humans; Nasal Sprays; Varenicline; Ophthalmic Solutions; Dry Eye Syndromes; Cyclosporine; Treatment Outcome
PubMed: 37096956
DOI: 10.57264/cer-2022-0215