A preliminary benefit-risk assessment of varenicline in smoking cessation.

Cochrane Tobacco Addiction Group, Department of Primary Health Care, Oxford University, Oxford, UK.
Drug Safety (Impact Factor: 2.62). 02/2009; 32(2):119-35. DOI: 10.2165/00002018-200932020-00005
Source: PubMed

ABSTRACT Varenicline is a recently developed medication for smoking cessation, which has been available on prescription since 2006. It is a selective nicotinic acetylcholine receptor partial agonist, and is designed to reduce withdrawal symptoms and to lessen the rewards of continued smoking. Our objective in this article is to assess the efficacy of varenicline as an aid to smoking cessation and to weigh the potential benefits against the possible risks. We identified ten randomized controlled trials and one cohort study with historical controls. In total there were 7999 participants, 5112 of whom received varenicline. Eight of the trials compared varenicline with placebo for cessation, two compared it with nicotine replacement therapy and one tested extended use for relapse prevention. Three of the varenicline/placebo trials also included a bupropion arm. The recommended dosage of varenicline 1 mg twice daily more than doubled the chances of quitting at 6 months or longer, with a relative risk (RR) compared with placebo of 2.38 (95% CI 2.00, 2.84). It also outperformed bupropion (RR 1.52 [95% CI 1.22, 1.88]) and nicotine replacement (RR 1.31 [95% CI 1.01, 1.71]). A reduced dosage regimen of 1 mg daily also increased cessation (RR 1.88 [95% CI 1.35, 2.60]). In the trials, varenicline significantly reduced craving and other withdrawal symptoms. The most frequent adverse event was nausea, occurring in 30-40% of varenicline users. However, this was generally reported at mild to moderate levels, diminished over time and was associated with attributable discontinuation rates of between 0.6% and 7.6%. Other commonly occurring adverse events included insomnia, abnormal dreams and headache. Serious adverse events were rare, with no treatment-related deaths during the treatment or follow-up phases. Postmarketing surveillance has raised new questions about the safety of varenicline. In February 2008, the US FDA issued a public health advisory note, reporting a possible association between varenicline and an increased risk of behaviour change, agitation, depressed mood, and suicidal ideation and behaviour. They have required the manufacturers to revise the labelling of varenicline and the Summary of Product Characteristics, and to issue a medication guide. It is arguable that much of the reported behavioural and mood changes may be associated with nicotine withdrawal, although some effects occurred in people who continued to smoke while taking the medication. In view of the potential, if unproven, risk that varenicline may be associated with serious neuropsychiatric adverse outcomes, patients attempting to quit smoking with varenicline, and their families and caregivers, should be alerted about the need to monitor for neuropsychiatric symptoms, including changes in behaviour, agitation, depressed mood, suicidal ideation and suicidal behaviour, and to report such symptoms immediately to the patient's healthcare provider.

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    ABSTRACT: Introduction: Chronic diseases represent the greatest burden of disease in Colombia for which smoking is the major risk factor. Objectives: To provide clinical practice recommendations based upon efficacy and safety of smoking cessation therapies for Colombian adults. Materials and methods: An adaptation of clinical practice guidelines (CPG) based on the ADAPT methodology was performed. We searched CPG on Medline, EMBASE, CINAHL, LILACS, and Cochrane databases. Six months’ cessation rates were appraised for brief and intensive counseling, nicotine replacement therapy (NRT), bupropion, varenicline, clonidine, nortriptyline, acupuncture, hypnosis, homeopathy, and combined treatments. CPG were evaluated with DELBI and selected when having a score above 60% for methodological rigor of development and applicability to the Colombian health system. Formal consensus was performed for questions without strong evidence. Results: 925 references were found, 17 CPG were pre-selected and 5 selected for adaptation. Brief and intensive counseling, NRT, bupropion, nortriptyline, and varenicline are effective for smoking cessation (cessation rates augment 5.1%-22.7%). Alternative therapies have not demonstrated cessation efficacy. Concomitant use of different NRT is the only combination with demonstrated efficacy (OR 1.9, 95%CI 1.3-2.7). Conclusions: Several alternatives for giving up tobacco smoking have confirmed efficacy. The absolute difference in cessation rates is variable among therapies and duration of effect requires further research. Brief and intensive counseling necessitate standardized formats for their implementation in Colombia. Economic evaluations are required to assess costs and benefits and to select the most suitable interventions for Colombia.
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    ABSTRACT: To compare the risk of suicide, self harm, and depression in patients prescribed varenicline or bupropion with those prescribed nicotine replacement therapy. Prospective cohort study within the Clinical Practice Research Datalink. 349 general practices in England. 119 546 men and women aged 18 years and over who used a smoking cessation product between 1 September 2006 and 31 October 2011. There were 81 545 users of nicotine replacement products (68.2% of all users of smoking cessation medicines), 6741 bupropion (5.6%), and 31 260 varenicline (26.2%) users. Outcomes were treated depression and fatal and non-fatal self harm within three months of the first smoking cessation prescription, determined from linkage with mortality data from the Office for National Statistics (for suicide) and Hospital Episode Statistics data (for hospital admissions relating to non-fatal self harm). Hazard ratios or risk differences were estimated using Cox multivariable regression models, propensity score matching, and instrumental variable analysis using physicians' prescribing preferences as an instrument. Sensitivity analyses were performed for outcomes at six and nine months. We detected 92 cases of fatal and non-fatal self harm (326.5 events per 100 000 person years) and 1094 primary care records of treated depression (6963.3 per 100 000 person years). Cox regression analyses showed no evidence that patients prescribed varenicline had higher risks of fatal or non-fatal self harm (hazard ratio 0.88, 95% confidence interval 0.52 to 1.49) or treated depression (0.75, 0.65 to 0.87) compared with those prescribed nicotine replacement therapy. There was no evidence that patients prescribed bupropion had a higher risk of fatal or non-fatal self harm (0.83, 0.30 to 2.31) or of treated depression (0.63, 0.46 to 0.87) compared with patients prescribed nicotine replacement therapy. Similar findings were obtained using propensity score methods and instrumental variable analyses. There is no evidence of an increased risk of suicidal behaviour in patients prescribed varenicline or bupropion compared with those prescribed nicotine replacement therapy. These findings should be reassuring for users and prescribers of smoking cessation medicines.
    BMJ (online) 10/2013; 347:f5704. · 16.38 Impact Factor