Varenicline In Patients Research Articles

Efficacy and Safety of Varenicline for Smoking Cessation in Patients With Type 2 Diabetes

Evidence of effective smoking cessation interventions in patients with diabetes is limited. The unique behavioral and metabolic characteristics of smokers with type 2 diabetes warrants a randomized clinical trial of the smoking cessation drug varenicline. To evaluate the efficacy and safety of varenicline in patients with type 2 diabetes with an intention to quit smoking. This multicenter, double-blind, placebo-controlled randomized clinical trial recruited patients from 6 outpatient clinics in 5 hospitals in Catania, Italy. Patients with type 2 diabetes, who were smoking at least 10 cigarettes a day, and who intended to quit smoking were screened for eligibility. Eligible patients were randomized to either varenicline or placebo treatment. The trial consisted of a 12-week treatment phase followed by a 40-week follow-up, nontreatment phase. Intention-to-treat data analysis was performed from December 2020 to April 2021. Varenicline, 1 mg, twice daily or matched placebo administered for 12 weeks. Patients in both treatment groups also received smoking cessation counseling. The primary efficacy end point of the study was the continuous abstinence rate (CAR) at weeks 9 to 24. Secondary efficacy end points were the CAR at weeks 9 to 12 and weeks 9 to 52 as well as 7-day point prevalence of abstinence at weeks 12, 24, and 52. A total of 300 patients (mean [SD] age, 57.4 [0.8] years; 117 men [78.0%] in varenicline group and 119 men [79.3%] in placebo group) were randomized to receive varenicline (n = 150) or placebo (n = 150). The CAR at weeks 9 to 24 was significantly higher for the varenicline than placebo group (24.0% vs 6.0%; odds ratio [OR], 4.95; 95% CI, 2.29-10.70; P < .001). The CARs at weeks 9 to 12 (31.3% vs 7.3%; OR, 5.77; 95% CI, 2.85-11.66; P < .001) and weeks 9 to 52 (18.7% vs 5.3%; OR, 4.07; 95% CI, 1.79-9.27; P < .001) as well as the 7-day point prevalence of abstinence at weeks 12, 24, and 52 were also significantly higher for the varenicline vs placebo group. The most frequent adverse events occurring in the varenicline group compared with the placebo group were nausea (41 [27.3%] vs 17 [11.4%]), insomnia (29 [19.4%] vs 19 [12.7%]), abnormal dreams (19 [12.7%] vs 5 [3.4%]), anxiety (17 [11.4%] vs 11 [7.3%]), and irritability (14 [9.4%] vs 8 [5.4%]). Serious adverse events were infrequent in both groups and not treatment-related. Results of this trial showed that inclusion of varenicline in a smoking cessation program is efficacious in achieving long-term abstinence without serious adverse events. Varenicline should be routinely used in diabetes education programs to help patients with type 2 diabetes stop smoking. ClinicalTrials.gov Identifier: NCT01387425.

Disappointing varenicline results offer important guidance for alcohol research

While showing disappointing results for the drug varenicline in patients with alcohol use disorder (AUD), a new study offers yet another recent confirmation that results observed in human laboratory analyses reflect participants' everyday behavior outside the lab.

Efficacy of Varenicline in Patients With Severe Alcohol Dependence: A Pilot Double-Blind Randomized and Controlled Study.

Varenicline has proven its efficacy in the treatment of nicotine dependence, and there is also evidence that it could be helpful in the treatment of alcohol dependence. In our pilot study, we investigated the feasibility and acceptability of varenicline for the treatment of a population of patients with severe alcohol dependence and multiple somatic comorbidities after alcohol detoxification. We conducted a phase II, double-blind, placebo-controlled randomized trial of daily oral varenicline versus a placebo in alcohol-dependent men and women after alcohol detoxification (n = 28). Following our study protocol, somatic conditions and adverse events were thoroughly monitored and several study end points were investigated (percentage of abstinent days for both alcohol and nicotine, number of standardized drinks and cigarettes per day, days of heavy drinking). Compared with the placebo, varenicline did not have more side effects and did not provoke more adverse events. Patients in the varenicline group did not show a significantly higher percentage of alcohol abstinent days or fewer heavy drinking days. A trend significance was found for a reduced number of standard drinks per day (P = 0.06) in the varenicline group. In this pilot trial, varenicline was shown to be well tolerated by our study population of severely alcohol-dependent patients with somatic conditions. Varenicline did not sustain alcohol abstinence or reduce the number of heavy drinking days, but it did reduce the daily amount of alcohol consumed.

The first results nicotine dependence treatment by varenicline in patients with tuberculosis

абакокурение не только способствует инфицированию туберкулезом, но и ухудшает эффективность лечения, увеличивая риски рецидивов туберкулеза, формирования множественной и широкой лекарственной устойчивости. Материалы и методы. Всего было обследовано 44 больных туберкулезом легких (от 21 до 60 лет). 17 больных согласились на включение в комплексную терапию туберкулеза варениклина (основная группа), 27 больных получили только индивидуальное телефонное консультирование (контрольная группа). При поступлении больных интервьюировали по статусу курения, степени никотиновой зависимости (тест Фагерстрома), опроснику «Адаптивность». Статистическая обработка данных проведена с помощью пакета прикладных программ SPSS. Результаты исследования. При отказе от табакокурения (ТК) у больных были зарегистрированы проявления синдрома отмены никотина: желание курить, раздражительность, ухудшение настроение, головная боль. В группе лечения варениклином тошнота встречалась чаще (на 3-й день приема в 29% случаев против 7,4% в контрольной группе; на 7-й день приема — в 24 и 15% соответственно; р&gt;0,05). Отказ от ТК состоялся на 7-й день приема препарата у 6 человек, 8 больных туберкулезом легких снизили (в 2 и более раз) число выкуриваемых в день сигарет. На 9-й день приема препарата не курили 8 человек, на 10-й день — 11 больных, на 12-й день не курили 14 человек из 17 (82%). В контрольной группе все больные назначили день отказа от табака и не курили в 84% случаев в день отказа от табакокурения. Через 30 дней в основной группе больных туберкулезом оставались некурящими в 41% случаев, в контрольной группе больных — 37 % (р&gt;0,05). Остальные больные и в основной, и в контрольной группах снизили число выкуриваемых в день сигарет не менее чем в два раза. Несмотря на некоторые проявления синдрома отмены, только 3 больных отказались от приема варениклина из-за тошноты, хотя надо отметить, что даже в контрольной группе, пациенты которой получали только стандартное лечение туберкулеза и индивидуальное консультирование при отказе от табака, тошнота отмечалась в 7,4–15% случаев. Это свидетельствует о том, что тошнота в некоторых случаях обусловлена проведением химиотерапевтического лечения туберкулеза, а не лечением синдрома зависимости от никотина. Заключение. Исследование показало, что большинство курящих больных туберкулезом легких нуждаются в помощи в отказе от табака и лечении никотиновой зависимости при отказе от табака, так как имеют среднюю и высокую степени никотиновой зависимости и выраженный синдром отмены при отказе от потребления табака. Лечение варениклином и индивидуальное телефонное консультирование являются эффективными вмешательствами для отказа от табакокурения больных туберкулезом. Варениклин в большинстве случаев (85%) хорошо переносился больными туберкулезом, получающими лечение основного заболевания.

Multimodal treatment for smoking cessation with varenicline in alcoholic, methadone-maintained, and psychotic patients: A one-year follow-up.

INTRODUCTIONNumerous studies have evaluated the efficacy and safety of varenicline for smoking cessation in smokers in the general population and, to a lesser extent, among the psychiatric population. However, few studies have evaluated varenicline in patients with other addictions. The present study was conducted to assess outcomes of a multimodal treatment for smoking cessation intervention with varenicline in a sample of alcohol and substance use disorders and patients with psychotic disorders.METHODSThis was a prospective, multicenter study. The patient sample comprised alcoholics in remission, methadone-maintained patients, and patients with psychotic disorders, all of whom wanted to stop smoking. All participants received multimodal treatment for smoking cessation therapy (psychological therapy plus varenicline). Smoking abstinence and changes in the psychopathological state of patients were assessed at predefined time points during a 12-month follow-up. The probability of tobacco abstinence after one year of treatment was computed using Kaplan-Meier life tables.RESULTSThe probability of abstinence at one year was 0.225 (95% CI: 0.1430-0.319). By group, the probabilities were as follows: patients with psychotic disorders 0.254 (95% CI: 0.118-0.415); alcoholics 0.237 (95% CI: 0.098-0.409); and methadone-maintained patients 0.177 (95% CI: 0.065-0.335). Patients with previous quit attempts had a higher probability of achieving abstinence at one year (p<0.01).CONCLUSIONSThe results of this study support the use of multimodal treatment with varenicline in patients with alcohol addiction in remission, patients on methadone maintenance, and patients with stable psychotic disorders. Previous smoking cessation attempts were predictive of smoking cessation success in these patients.

Budgetary Impact Analysis of Reimbursement Varenicline for the Smoking-Cessation Treatment in Patients with Cardiovascular Diseases, Chronic Obstructive Pulmonary Disease or Type-2 Diabetes Mellitus: A National Health System Perspective

Aims: The study aimed to assess the budgetary impact (BI) of reimbursing varenicline in patients with chronic obstructive pulmonary disease (COPD), type-2 diabetes mellitus (t2-DM) or cardiovascular diseases (CVD). Methods: The BI was estimated comparing the current non-reimbursed scenario versus a projected reimbursed scenario using the Spanish National Health System (SNHS) perspective. A hybrid model was developed using epidemiological data and Markov chains to estimate smoking cessation rates with varenicline during a 5-year horizon. Costs of cessation were considered in the reimbursement scenario only. Efficacy, expressed as a 1-year continuous abstinence rate, was derived from clinical trials. Cost savings due to smoking cessation were extracted from local cost-of-illness studies. Results are shown as incremental cost savings. Univariate sensitivity analysis was also applied. Results: A total of 68,684 patients stopped smoking in the reimbursed scenario compared with 15,208 without reimbursement. In the reimbursed scenario, total savings accounted for €36.3 million, showing 14.6 million accumulated additional savings compared with the scenario without reimbursement. Sensitivity analyses showed results to be robust with monetary savings starting in the third year of modeling. Conclusion: Reimbursement of varenicline in smoking cessation is a cost-effective health policy in the SNHS in COPD, t2-DM or CVD, and could produce cost savings starting in the third year of implementation.

Pharmacotherapy of Tobacco Use Disorder

Pharmacotherapy of Tobacco Use Disorder

Safety of Varenicline in Patients With Cardiovascular Disease

Smoking cessation lowers the risk of death substantially in patients with cardiovascular disease. Although varenicline is an effective medication for smoking cessation, its safety in this population has been questioned and evaluated in several studies. In 2 randomized controlled trials of patients with cardiovascular disease, the rates of serious cardiovascular events were up to 2% higher in patients receiving varenicline than placebo, though the differences were not statistically significant. In the first meta-analysis of mostly trials involving patients with a history of cardiovascular disease, varenicline was found to significantly increase the risk of cardiovascular events by 72%; however, a second meta-analysis did not find a significant increased risk. In an observational study, varenicline was not associated with an increased risk of events when compared to bupropion in a subgroup analysis of patients with a history of cardiovascular disease. Because the evidence on the safety of varenicline in this population is limited and conflicting, additional data are needed to formulate stronger conclusions. In the meantime, health care professionals should consider individual smoking patterns, concomitant medical conditions, and cost when recommending smoking cessation pharmacotherapy for patients with cardiovascular disease.

Neuropsychiatric Adverse Events of Varenicline

Over the past years, the impact of varenicline in patients with mental illness has been debated as serious neuropsychiatric adverse events (AEs) have been reported with varenicline use. To identify and summarize published case reports of neuropsychiatric AEs ascribed to varenicline and to determine potential risk factors for these AEs. A literature search of MEDLINE, the Cochrane Library, EMBASE, and PsychInfo database was conducted for case reports concerning the neuropsychiatric AEs of varenicline published in English from 2006 (approval year by the US Food and Drug Administration and the Dutch Medicines Evaluation Board) to January 1, 2012. We identified 25 published cases. In most reports, patients had been admitted to psychiatric hospitals with serious neuropsychiatric AEs due to varenicline. The average patient age was 46.4 years, and 56% were men; 68% of patients had a psychiatric history. The onset of symptoms started 2 days to 3 months after the initiation of varenicline. One report described completed suicide in a man with no psychiatric history. In most cases (84%), the neuropsychiatric symptoms resolved after the discontinuation of varenicline. Analysis of all reports using the Naranjo causality scale, a method for estimating the probability of adverse drug reactions, indicated probable causality in 76% of the cases and definite causality in 12% of cases. Varenicline is associated with an increased risk of serious neuropsychiatric AEs, especially in patients with a psychiatric illness. It is strongly recommended that varenicline be administered only to mentally stable patients and under close monitoring.

Does Varenicline Worsen Psychiatric Symptoms in Patients With Schizophrenia or Schizoaffective Disorder?

To review published cases and prospective studies describing the use of varenicline in patients with schizophrenia and schizoaffective disorder. PubMed, PsychINFO, and the Cochrane Database were searched in July 2011 using the key words schizophrenia, schizoaffective disorder, psychosis, positive symptoms, negative symptoms, aggression, hostility, suicidal ideation AND varenicline to identify reports published between January 2006 and July 2011 in English. Five case reports, 1 case series, 1 retrospective study, 10 prospective studies (17 publications), and 1 meeting abstract describing the use of varenicline in patients with schizophrenia or schizoaffective disorder were identified. Review articles and articles describing findings other than the use of varenicline in patients with schizophrenia or schizoaffective disorder were excluded. Thirteen reports were included in the final analysis. Information on each study's patient population, age, diagnosis, medication treatment, tobacco use history, adverse effects, and outcome was collected from the published reports. Of the 260 patients with schizophrenia or schizoaffective disorder who received varenicline in these published reports, 13 patients (5%) experienced the onset or worsening of any psychiatric symptom, although 3 of the 13 patients experienced a very brief negative effect after 1 dose. No patients experienced suicidal ideation or suicidal behaviors. Published reports suggest that, in most stable, closely monitored patients with schizophrenia or schizoaffective disorder, varenicline treatment is not associated with worsening of psychiatric symptoms. Current, prospective studies are assessing effectiveness and further assessing safety in this population.

Varenicline for smoking cessation intervention in chronic obstructive pulmonary disease

Introduction:In smoking-related chronic obstructive pulmonary disease (COPD), smoking cessation was previously demonstrated to reduce lung function decline and disease morbidity if it resulted in a sustained tobacco abstinence. Varenicline is a newer pharmacologic therapeutic agent able to reduce withdrawal symptoms in smokers, and this makes it particularly valuable in inducing abstinence in patients with significant addiction.Areas covered:This paper discusses the results of a randomized, placebo-controlled study evaluating the effects of a smoking cessation intervention including varenicline in patients with COPD.Expert opinion:Varenicline can be an appropriate aid to maintaining smoking abstinence in patients with COPD and heavier nicotine addiction, and the documentation of the long-term effects of a smoking cessation intervention that includes this pharmacologic therapeutic agent is necessary.

Response to Letter Regarding Article, “Efficacy and Safety of Varenicline for Smoking Cessation in Patients With Cardiovascular Disease: A Randomized Trial”

In their letter, Drs Smolderen and Pelle correctly point out that patients with cardiovascular disease (CVD) have a high rate of comorbid depression, that depressed patients have less success when they attempt to stop smoking, and that the exclusion of smokers with comorbid depression from our trial of varenicline in patients with CVD limits our ability to generalize the results of our study to all smokers with CVD, as we had noted in the original article.1 As they request, we clarify here why our trial excluded CVD patients with comorbid depression. According to standard methodology used in testing new drugs, medications not specifically intended for psychiatric indications are …

Varenicline use in patients with mental illness: an update of the evidence

Importance of the field: Patients with a psychiatric diagnosis have a higher prevalence of smoking compared to the general population. Varenicline is a first-line pharmacotherapy option to assist in smoking cessation. Clinical trials during drug development excluded patients with active psychiatric illnesses leaving the risks associated with varenicline use in this patient population unknown.Areas covered in this review: Literature published in English up to December 2009 were identified and include neuropsychiatric adverse drug events reported in pre-marketing trials and post-marketing surveillance, varenicline case reports, evidence surrounding the use of varenicline in patients with psychiatric diagnoses, and varenicline and suicidality.What the reader will gain: Although the risk of potential neuropsychiatric events is evident through voluntary reporting systems and reported cases in the literature, multiple studies and case reports support the use of varenicline in the mental health population. Reviewing the literature will enable clinicians to optimize patient care by weighing the risks and benefits associated with varenicline use against the risk of continued smoking.Take home message: Cautious treatment initiation, patient education, and close follow-up, monitoring for mood and behavior changes during therapy are recommended, especially in the psychiatric setting.

Psychiatric, Suicide Risks Lead to Warning on Smoking-Cessation Drugs

Back to table of contents Previous article Next article Government NewsFull AccessPsychiatric, Suicide Risks Lead to Warning on Smoking-Cessation DrugsJun YanJun YanSearch for more papers by this authorPublished Online:7 Aug 2009https://doi.org/10.1176/pn.44.15.0006aAfter reviewing postmarketing reports, the Food and Drug Administration (FDA) has ordered a boxed warning for two smoking-cessation drugs, varenicline and bupropion, regarding the risks of neuropsychiatric adverse reactions and suicide. Credit: iStockphoto ©Lukasz WitczakIn addition to the boxed warning in the product labels, the drugs' manufacturers are required to develop medication guides to inform patients about these risks. Buproprion already carries another boxed warning about suicidality risk in children, adolescents, and young adults that is standard for all antidepressants.In the July 1 announcement of the new safety alert, the FDA urged health care professionals to explain the neuropsychiatric risks to patients receiving treatment for smoking cessation. Patients should be told to “stop taking varenicline or bupropion and contact a health care provider immediately if they experience agitation, depressed mood, and any changes in behavior that are not typical of nicotine withdrawal, or if they experience suicidal thoughts or behaviors,” the agency stated.The FDA analyzed hundreds of postmarketing case reports of neuropsychiatric symptoms and suicidal thoughts or behaviors suspected of being connected to the use of smoking-cessation aids. Between its approval in 2006 and November 2007, varenicline was linked to 116 cases of suicidal ideation and 37 suicidal behaviors, including 19 deaths, according to a review published in FDA Drug Safety Newsletter (volume 2, number 1). For bupropion, 46 cases of suicidal ideation and 29 of suicidal behaviors, including 10 deaths, were associated with the drug since 1997, when it was approved for smoking cessation as Zyban.In the review, suicidal behaviors referred to reports that included the phrases “completed suicide,” “attempted suicide,”“ intentional self-injury,” “self-injurious behavior,”“ suicidal behavior,” “multiple drug overdose,”“ gun-shot wound,” “intentional misuse,” and“ overdose.”Half of the patients with varenicline-linked suicidal ideation and behaviors had a known history of psychiatric disorders, a quarter had no psychiatric history, and psychiatric-disorder history was unknown for the rest.FDA reviewers also considered adverse-event reports associated with nicotine-replacement patches such as Nicoderm, Habitrol, and Prostep, but found no clear link to suicidal ideation or behaviors.Because the FDA's adverse-event reporting system relies on spontaneous, voluntary reports from health care professionals and the public, the case numbers probably have underestimated the true frequency of suicidal ideation and behaviors. Both drugs have been sold in millions of units since receiving approval, according to the agency.At a press briefing on July 1, Curtis Rosebraugh, M.D., director of the FDA's Office of Drug Evaluation II, acknowledged that nicotine withdrawal itself can cause psychiatric symptoms similar to those suspected with varenicline and bupropion, and this overlap makes it difficult to analyze the true effects of the drugs. He also emphasized that neither drug has been deemed contraindicated in any patient population and that the risks must be weighed carefully with the health benefits of smoking cessation.“The question for clinicians to consider is what the relative risks are between drug-related adverse events and the consequences of smoking,” John Newcomer, M.D., told Psychiatric News. Newcomer is the Gregory B. Couch Professor of Psychiatry and a professor of psychology and medicine at Washington University in St. Louis School of Medicine.“ The risk of failing to achieve smoking cessation is clear and large. The FDA warning is nicely phrased to point out the need for careful clinical evaluation of the risks and benefits of these drugs.” He pointed out that smoking cessation has been shown to result in rapid and substantial reduction in the risk of cardiovascular and pulmonary diseases.Smoking cessation may have particularly high priority in psychiatry because certain psychiatric disorders, such as schizophrenia, are associated with much higher rates of smoking than are found among the general population. Meanwhile, psychiatric patients taking antipsychotic and other medications are already facing elevated risks of metabolic and cardiovascular diseases, with smoking potentially multiplying those risks.“Psychiatric populations may or may not be more susceptible to the neuropsychiatric effects of the [smoking-cessation] drugs, but we do not have the answer now,” said Newcomer. An ongoing clinical trial of varenicline in patients with schizophrenia may eventually provide data on this question.Monitoring for psychiatric symptoms emerging while a person is taking smoking-cessation medications is important. “The [drug-related] adverse events are very difficult to disentangle from smoking cessation itself,” said Newcomer. He pointed out that, for the average patient, the side effects of varenicline or bupropion appear to be incremental above the side effects of nicotine withdrawal, which should be monitored regardless of the smoking-cessation method.For now, clinicians should “sit down with the patient and make careful decisions together,” Newcomer recommended.The FDA alert is posted at<www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm169986.htm>. The agency's postmarketing review of suicidal ideation and behaviors is posted at<www.fda.gov/downloads/Drugs/DrugSafety/DrugSafetyNewsletter/UCM107318.pdf>.▪ ISSUES NewArchived

Cognitive and antismoking effects of varenicline in patients with schizophrenia or schizoaffective disorder

Objective Varenicline has been shown to be an effective anti-smoking treatment in smokers without identified psychiatric illness, and the drug's pharmacology suggests possibilities of pro-cognitive effects. However, recent reports suggest varenicline may have the potential for important psychiatric side-effects in some people. We present the first prospective quantitative data on the effects of varenicline on cognitive function, cigarette smoking, and psychopathology in a small sample of schizophrenic patients. Method Fourteen schizophrenic smokers were enrolled in an open-label study of varenicline with a pre-post design. Measures of cognitive function (RBANS, Virtual Water-Maze Task), cigarette smoking (cotinine levels, CO levels, self-reported smoking and smoking urges), and psychopathology (PANSS) were evaluated prior to and during treatment with varenicline. Data on psychopathology changes among schizophrenic smokers in another drug study, in which patients were not receiving varenicline, were used for comparison. Results 12 patients completed the study, and 2 patients terminated in the first two weeks of active varenicline because of complaints of nausea or shaking. Varenicline produced significant improvements in some cognitive test scores, primarily associated with verbal learning and memory, but not in scores on visual-spatial learning or memory, or attention. Varenicline significantly decreased all indices of smoking, but did not produce complete smoking abstinence in most patients. During treatment with varenicline there were no significant increases in psychopathology scores and no patient developed signs of clinical depression or suicidal ideation. Conclusions Our small prospective study suggests that treatment with varenicline appears to have some beneficial cognitive effects which need to be confirmed in larger studies with additional neuropsychological tests. Varenicline appears to have some anti-smoking efficacy in schizophrenia but longer studies are needed to determine whether it will produce rates of smoking abstinence similar to those found in control smokers. Treatment with varenicline may not increase psychopathology or depression in most patients with schizophrenia, but we cannot accurately estimate the absolute risk of a potentially rare side-effect from this small sample.

Varenicline may trigger severe hypoglycaemia in Type 1 diabetes

Varenicline is a new drug indicated for smoking cessation. It has primarily been investigated in healthy adults. The commonest side-effects are nausea, headache, sleep disturbance, constipation, flatulence and vomiting. Hypoglycaemia has not been reported. As smoking cessation is important to reduce risk of cardiovascular morbidity, especially in diabetes, use of effective drugs indicated for smoking cessation is rational. We report multiple episodes of severe hypoglycaemia after starting varenicline in a 53-year-old woman with Type 1 diabetes. Since onset of diabetes at age 25 years and until start of varenicline therapy, she had only experienced one episode of severe hypoglycaemia and hypoglycaemia awareness was not impaired. The severe hypoglycaemic episodes disappeared after withdrawal of varenicline. We recommend cautious prescription of varenicline, intensified blood glucose monitoring and careful education of patients with diabetes treated with varenicline. Further investigation of the use of varenicline in patients with diabetes is warranted.