Cessation Drugs Science News

Effect of Varenicline on Individual Nicotine Withdrawal Symptoms: A Combined Analysis of Eight Randomized, Placebo-Controlled Trials.

Nicotine Tob Res. 2013 May 21;

Authors: Foulds J, Russ C, Yu CR, Zou KH, Galaznik A, Franzon M, Berg A, Hughes JR

Abstract
INTRODUCTION: Concerns exist that varenicline may cause neuropsychiatric side effects. Some of these symptoms (e.g., depression, irritability) have been measured in clinical trials using nicotine withdrawal scales. This study assessed the effect of varenicline on neuropsychiatric and other symptoms, as measured by the Minnesota Nicotine Withdrawal Scale (MNWS). METHODS: We analyzed weekly individual MNWS symptom ratings in 8 randomized double-blind, placebo-controlled smoking cessation trials funded by Pfizer with similar methodology (n = 2,403 varenicline; n = 1,434 placebo). Ratings for the past 24hr were obtained prior to quitting and starting treatment and at Weeks 1-6 and 11 after the quit date. RESULTS: In repeated measures analyses controlling for baseline values, ratings for 5 neuropsychiatric symptoms (depressed mood, irritability, anxiety, difficulty concentrating, and restlessness) and urge to smoke were lower (p < .01) for varenicline than placebo at each timepoint. Worsening in scores from 0-2 (baseline) to 4 was less frequent on varenicline than placebo for all ratings except appetite- (significantly more frequent for varenicline, p < .0001) and sleep-related items. Repeated measures analysis for individuals with low levels of exhaled carbon monoxide revealed similar patterns except for a nonsignificant difference for increased appetite. CONCLUSIONS: Use of varenicline while trying to quit smoking reduces and does not increase neuropsychiatric symptoms such as depressed mood and irritability measured on the MNWS in smokers without current psychiatric disorders. It is associated with increases in sleep disturbance and appetite although the latter appears due to enabling more subjects to abstain from smoking.

PMID: 23694782 [PubMed - as supplied by publisher]

The pharmacist "toolbox" for smoking cessation: a review of methods, medicines, and novel means to help patients along the path of smoking reduction to smoking cessation.

J Pharm Pract. 2012 Dec;25(6):591-9

Authors: Wynn WP, Stroman RT, Almgren MM, Clark KJ

Abstract
Annually there are 500 000 preventable deaths in the United States caused by smoking; as health care professionals, pharmacists have a unique opportunity to advise, assess, and assist patients to quit smoking. This review article provides pharmacists with a "toolbox" containing an overview of pharmacologic and nonpharmacologic methods for smoking cessation. Currently approved over-the-counter (OTC) and prescription medications (nicotine replacement therapy, varenicline, and bupropion) are summarized, and nonpharmacologic therapies discussed include cognitive therapy and hypnosis. In addition to traditional therapies some potential approaches to smoking cessation are addressed, including nicotine immunizations and electronic cigarettes.

PMID: 23222855 [PubMed - indexed for MEDLINE]

An Unusual Pattern of Ligand-Receptor Interactions for the ?7 Nicotinic Acetylcholine Receptor, with Implications for the Binding of Varenicline.

Mol Pharmacol. 2013 May 16;

Authors: Van Arnam EB, Blythe EE, Lester HA, Dougherty DA

Abstract
The ?7 nicotinic acetylcholine receptor shows broad pharmacology, complicating the development of subtype-specific nicotinic receptor agonists. Here we use unnatural amino acid mutagenesis to characterize binding to ?7 by the smoking cessation drug varenicline (Chantix), an ?4?2-targeted agonist that shows full efficacy and modest potency at the ?7 receptor. We find that unlike binding to its target receptor, varenicline does not form a cation-? interaction with TrpB, further supporting a unique binding mode for the cationic amine of nicotinic agonists at the ?7 receptor. We also evaluate binding to the complementary face of the receptor's binding site by varenicline, the endogenous agonist acetylcholine, and the potent nicotine analog epibatidine. Interestingly, we find no evidence for functionally significant interactions involving backbone NH and CO groups thought to bind the canonical agonist hydrogen bond acceptor of the nicotinic pharmacophore, perhaps reflecting a lesser importance of this pharmacophore element for ?7 binding. We also show that the Trp55 and Leu119 side chains of the binding site's complementary face are important for the binding of the larger agonists epibatidine and varenicline, but dispensable for binding of the smaller, endogenous agonist acetylcholine.

PMID: 23680636 [PubMed - as supplied by publisher]

Effectiveness of varenicline as an aid to smoking cessation in primary care: an observational study.

Eur Addict Res. 2013;19(1):47-54

Authors: Andreas S, Chenot JF, Diebold R, Peachey S, Mann K

Abstract
AIMS: Although varenicline is commonly prescribed in primary care, information on smoking-related comorbidities and the effectiveness of varenicline in this context in Germany is scarce. This study assessed the efficacy and safety of varenicline in a large sample of patients seeking smoking cessation treatment through their general practitioners. The frequency of comorbidities was also evaluated.
METHODS: This was a 12-week, prospective, observational, non-comparative phase IV trial conducted in Germany. Abstinence rates at week 12 were evaluated by verbal reporting using the nicotine use inventory.
RESULTS: Overall, 1,391 subjects were enrolled; 1,177 received study medication and were evaluated for effectiveness and safety. At the end of the study, 71.1% (95% confidence interval 68.5-73.7) of subjects were abstinent. There were a total of 205 all-causality adverse events; 2.2% were classified as serious or severe. There were no fatal adverse events. At inclusion, 66.7% of participants had at least 1 concurrent comorbidity, with chronic obstructive pulmonary disease (35.5%), hypertension (29.6%) and depression (10.4%) being the most commonly reported.
CONCLUSION: These real-world data indicate that varenicline is an effective and well-tolerated smoking cessation treatment when used in the primary care setting including patients with smoking-related comorbidities.

PMID: 22987095 [PubMed - indexed for MEDLINE]

Fifty-two-week continuous abstinence rates of smokers being treated with varenicline versus nicotine replacement therapy.

Addiction. 2013 May 13;

Authors: Kralikova E, Kmetova A, Stepankova L, Zvolska K, Davis R, West R

Abstract
BACKGROUND AND AIMS: Cross-study comparisons of effect sizes suggest that varenicline is more effective than nicotine replacement therapy (NRT) in aiding smoking cessation, but evidence from direct comparisons is limited. This study compared biochemically verified 52-week sustained abstinence rates in smokers attending the same clinical service according to whether they used varenicline or NRT in their quit attempt. METHODS: This was a prospective cohort study of 855 smokers attending a large smoking cessation clinic who used their choice of NRT product or varenicline in their quit attempt. All received the same behavioural support programme and chose their medication option (n?=?519 varenicline; n?=?336 NRT). The primary outcome measure was self-report of 52 weeks' abstinence following the target quit date confirmed by expired air carbon monoxide concentration. Baseline measures included socio-demographic variables, mental health diagnoses, measures of smoking, cigarette dependence and past use of NRT or varenicline. RESULTS: The 52-week abstinence rates were 42.8% versus 31.0% in those using varenicline versus NRT, respectively (P?<?0.001). After adjusting for all baseline variables, the odds of remaining abstinent for 52 weeks were 2.03 (95% CI 1.46-2.82), P?<?0.001 times higher in those using varenicline than those using NRT. CONCLUSIONS: Smokers in the same behavioural support programme who use varenicline appear to have a greater probability of achieving long-term abstinence than those using their choice of nicotine replacement therapy options, even after adjusting for potentially confounding smoker characteristics.

PMID: 23668486 [PubMed - as supplied by publisher]

Commentary on "The Effectiveness of Varenicline Medication Guide for Conveying Safety Information to Patients: a REMS Assessment Survey" by Enger et al.

Pharmacoepidemiol Drug Saf. 2013 May 9;

Authors: Dal Pan GJ

PMID: 23661561 [PubMed - as supplied by publisher]

Neuropsychiatric Events with Varenicline: a Modified Prescription-Event Monitoring Study in General Practice in England.

Drug Saf. 2013 May 9;

Authors: Buggy Y, Cornelius V, Fogg C, Kasliwal R, Layton D, Shakir SA

Abstract
BACKGROUND: Varenicline (Champix(®)), launched in the UK in December 2006, is indicated for the treatment of smoking cessation in adults (?18 years of age). In 2008, the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK issued a warning suggesting that varenicline was associated with disparate neuropsychiatric symptoms, including depression, suicidal thoughts and behaviour. In response to this regulatory warning, the Drug Safety Research Unit conducted a modified prescription-event monitoring (M-PEM) study to monitor the safety of varenicline. OBJECTIVE: The aim of this study was to estimate the incidence and examine the pattern of neuropsychiatric events reported to general practitioners (GPs) in England during the immediate postmarketing period for varenicline. METHODS: A postmarketing surveillance study was conducted using the observational cohort technique of M-PEM. Patients were identified from dispensed prescriptions issued by primary care physicians between December 2006 and March 2007. Data on exposure, previous history of psychiatric illness and events reported during and after treatment were collected from questionnaires. In order to determine whether hazards for neuropsychiatric events of interest (depression, anxiety, aggression, suicidal ideation, non-fatal self-harm) were non-constant over time (which could indicate a possible association with the drug), the pattern of events was examined by plotting the smoothed hazard function estimate and then fitting a Weibull model. The Weibull model shape parameter (?) and 95 % confidence interval were used as a test for a non-constant hazard function (where a value of 1 indicates a constant hazard over time). In addition to this analysis, the difference in incidence densities (IDs) between month 1 and months 2-3 were calculated and compared. RESULTS: The cohort comprised of 12,159 patients (median age 47 years [interquartile range 19]; 56.9 % [n = 6924 female]). The number of events reported during treatment, reason for stopping, adverse drug reactions (ADRs), and the p-value for the Weibull shape parameter were as follows: depression (n = 94; 42; 19; p = 0.144); anxiety (n = 94; 49; 9; p = 0.009); aggression (n = 7; 4; 2; p = 0.465); suicidal ideation (n = 8; 4; 1; p = 0.989) and non-fatal self-harm (n = 5; 1; 0; p = 0.771). No differences in the IDs between months 1 and months 2-3 were found for any of the events. CONCLUSION: Whilst between 7 and 17 % of neuropsychiatric events were attributed to the drug by GPs and approximately 20-50 % were given as reasons for stopping, no signal was raised using the ID differences approach, and only anxiety was flagged as a potential signal for an ADR using the Weibull model. The signal for anxiety requires further evaluation to determine whether the drug plays a part in the development of anxiety or whether it is a withdrawal symptom caused by smoking cessation. Analysis methods will lack power when the numbers of events are low even when a large number of participants are included in the study.

PMID: 23657823 [PubMed - as supplied by publisher]

Adapting Smoking Cessation Treatment According to Initial Response to Precessation Nicotine Patch.

Am J Psychiatry. 2013 May 3;

Authors: Rose JE, Behm FM

Abstract
OBJECTIVE The authors evaluated an adaptive smoking cessation treatment strategy in which nicotine patch treatment was initiated before a quit date, and then, depending on initial therapeutic response, either the nicotine patch was continued or alternative pharmacotherapies were provided. METHOD The study was a double-blind, parallel-arm adaptive treatment trial. A total of 606 cigarette smokers started open-label nicotine patch treatment 2 weeks before the quit date. Those whose ad lib smoking did not decrease by &gt;50% after 1 week were randomly assigned to one of three double-blind treatments: nicotine patch alone (control condition); "rescue" treatment with bupropion augmentation of the patch; or rescue treatment with varenicline alone. Participants whose precessation smoking decreased &gt;50% but who lapsed after the quit date were also randomly assigned to the two rescue treatments or to nicotine patch alone. Logistic regression analyses compared each rescue treatment against the control condition in terms of abstinence at the end of treatment (weeks 8-11) and at 6 months. RESULTS Smokers who did not respond adequately to precessation nicotine patch benefited from bupropion augmentation; abstinence rates at end of treatment were 16% with nicotine patch alone and 28% with bupropion augmentation (odds ratio=2.04, 95% CI=1.03-4.01). Switching to varenicline produced less robust effects, but point abstinence at 6 months was 6.6% with the patch alone and 16.5% with a switch to varenicline (odds ratio=2.80, 95% CI=1.11-7.06). Postquit adaptive changes in treatment had no significant effects on any abstinence outcome. CONCLUSIONS It is possible to rescue a significant portion of smokers who would have failed to achieve abstinence if left on nicotine patch alone by identifying these smokers before their quit date and implementing adaptive changes in treatment.

PMID: 23640009 [PubMed - as supplied by publisher]

Neuronal nicotinic acetylcholine receptors: common molecular substrates of nicotine and alcohol dependence.

Front Psychiatry. 2013;4:29

Authors: Hendrickson LM, Guildford MJ, Tapper AR

Abstract
Alcohol and nicotine are often co-abused. As many as 80-95% of alcoholics are also smokers, suggesting that ethanol and nicotine, the primary addictive component of tobacco smoke, may functionally interact in the central nervous system and/or share a common mechanism of action. While nicotine initiates dependence by binding to and activating neuronal nicotinic acetylcholine receptors (nAChRs), ligand-gated cation channels normally activated by endogenous acetylcholine (ACh), ethanol is much less specific with the ability to modulate multiple gene products including those encoding voltage-gated ion channels, and excitatory/inhibitory neurotransmitter receptors. However, emerging data indicate that ethanol interacts with nAChRs, both directly and indirectly, in the mesocorticolimbic dopaminergic (DAergic) reward circuitry to affect brain reward systems. Like nicotine, ethanol activates DAergic neurons of the ventral tegmental area (VTA) which project to the nucleus accumbens (NAc). Blockade of VTA nAChRs reduces ethanol-mediated activation of DAergic neurons, NAc DA release, consumption, and operant responding for ethanol in rodents. Thus, ethanol may increase ACh release into the VTA driving activation of DAergic neurons through nAChRs. In addition, ethanol potentiates distinct nAChR subtype responses to ACh and nicotine in vitro and in DAergic neurons. The smoking cessation therapeutic and nAChR partial agonist, varenicline, reduces alcohol consumption in heavy drinking smokers and rodent models of alcohol consumption. Finally, single nucleotide polymorphisms in nAChR subunit genes are associated with alcohol dependence phenotypes and smoking behaviors in human populations. Together, results from pre-clinical, clinical, and genetic studies indicate that nAChRs may have an inherent role in the abusive properties of ethanol, as well as in nicotine and alcohol co-dependence.

PMID: 23641218 [PubMed - in process]

Adapting Smoking Cessation Treatment According to Initial Response to Precessation Nicotine Patch.

Am J Psychiatry. 2013 May 3;

Authors: Rose JE, Behm FM

Abstract
OBJECTIVE The authors evaluated an adaptive smoking cessation treatment strategy in which nicotine patch treatment was initiated before a quit date, and then, depending on initial therapeutic response, either the nicotine patch was continued or alternative pharmacotherapies were provided. METHOD The study was a double-blind, parallel-arm adaptive treatment trial. A total of 606 cigarette smokers started open-label nicotine patch treatment 2 weeks before the quit date. Those whose ad lib smoking did not decrease by &gt;50% after 1 week were randomly assigned to one of three double-blind treatments: nicotine patch alone (control condition); "rescue" treatment with bupropion augmentation of the patch; or rescue treatment with varenicline alone. Participants whose precessation smoking decreased &gt;50% but who lapsed after the quit date were also randomly assigned to the two rescue treatments or to nicotine patch alone. Logistic regression analyses compared each rescue treatment against the control condition in terms of abstinence at the end of treatment (weeks 8-11) and at 6 months. RESULTS Smokers who did not respond adequately to precessation nicotine patch benefited from bupropion augmentation; abstinence rates at end of treatment were 16% with nicotine patch alone and 28% with bupropion augmentation (odds ratio=2.04, 95% CI=1.03-4.01). Switching to varenicline produced less robust effects, but point abstinence at 6 months was 6.6% with the patch alone and 16.5% with a switch to varenicline (odds ratio=2.80, 95% CI=1.11-7.06). Postquit adaptive changes in treatment had no significant effects on any abstinence outcome. CONCLUSIONS It is possible to rescue a significant portion of smokers who would have failed to achieve abstinence if left on nicotine patch alone by identifying these smokers before their quit date and implementing adaptive changes in treatment.

PMID: 23640009 [PubMed - as supplied by publisher]

Therapeutic doses of antidepressants are projected not to inhibit human ?4?2 nicotinic acetylcholine receptors.

Neuropharmacology. 2013 Apr 29;

Authors: Weber ML, Hofland CM, Shaffer CL, Flik G, Cremers T, Hurst RS, Rollema H

Abstract
Inhibition of central ?4?2 nAChRs by antidepressants, proposed to contribute to their clinical efficacy, was assessed for monoamine reuptake inhibitors (amitriptyline, nortriptyline, fluoxetine, sertraline, paroxetine, citalopram) by comparing projected human unbound brain drug concentrations (Cu,b) at therapeutic doses with concentrations that inhibit human ?4?2 nAChRs in vitro. Inhibitory concentrations (IC50) were determined by patch clamp and ranged from 0.8-3.2 ?M, except for nortriptyline (IC50=100 nM). Cu,b values were calculated from human unbound plasma drug concentrations (Cu,p) and rat-derived brain-to-plasma and extracellular fluid-to-plasma ratios for the unbound drug, which are near unity, due to much higher brain tissue binding than plasma protein binding of these drugs. Accordingly in humans, antidepressant Cu,b are projected to essentially equal Cu,p, with average values from 3-87 nM, which are 30-to-250-fold below their IC50 concentrations. Based on our model, monoaminergic antidepressants minimally inhibit central nAChRs and it is unlikely that ?4?2 nAChR antagonism contributes to their antidepressant activity. Nortriptyline is an exception with a Cu,b that is 2-fold below its IC50, which is comparable to the nAChR antagonist (±)-mecamylamine, for which Cu,b is 4-fold below its IC50; both drugs will inhibit a substantial fraction of ?4?2 nAChRs. The Cu,b of the ?4?2 nAChR partial agonist varenicline, which has antidepressant-like activity in a murine model, is higher than its IC50 and varenicline is projected to cause ?70% inhibition of ?4?2 nAChRs. Taken together these data may help explain the negative outcome of recent antidepressant augmentation trials with mecamylamine and the partial agonist CP-601927.

PMID: 23639435 [PubMed - as supplied by publisher]

Varenicline plus healthy lifestyle intervention for smoking cessation in psychotic disorders.

Ann Clin Psychiatry. 2012 Nov;24(4):285-91

Authors: Castle D, Baker AL, Richmond R, Filia SL, Harris D, Pirola-Merlo AJ

Abstract
BACKGROUND: We were interested in exploring the efficacy and safety of varenicline as an adjunct to a healthy lifestyle intervention for smoking cessation among individuals with a severe mental illness.
METHODS: We used varenicline as an adjunct to a healthy lifestyle intervention in 14 smokers with a psychotic illness.
RESULTS: Overall, smoking cessation rates were 36% at 3 months and 42% at 6 months. The most commonly reported side effects were sleep disturbance and nausea. These tended to occur early in treatment, and patients responded to general measures of support and reassurance. Of the 14 participants, 1 dropped out because of psychiatric problems and 2 because of other side effects.
CONCLUSIONS: Varenicline appears to be an effective adjunct to a healthy lifestyle intervention for smokers with a psychotic illness. Although the results of this open study are encouraging, replication in an adequately powered, randomized controlled trial is required before definitive conclusions can be drawn.

PMID: 23145385 [PubMed - indexed for MEDLINE]

Cigarette craving and withdrawal symptoms during temporary abstinence and the effect of nicotine gum.

Psychopharmacology (Berl). 2013 May 2;

Authors: Brown J, Hajek P, McRobbie H, Locker J, Gillison F, McEwen A, Beard E, West R

Abstract
RATIONALE: It is widely believed that nicotine withdrawal symptoms appear within a few hours of stopping smoking, but few data exist documenting their emergence in naturalistic settings. In several countries, nicotine replacement products are licensed for relief of withdrawal symptoms during temporary abstinence, but again, there are no data supporting this from naturalistic settings. OBJECTIVES: To examine the emergence of cigarette craving and withdrawal symptoms during temporary abstinence in a naturalistic setting while using either nicotine or placebo gum. METHODS: Double-blind, randomised, placebo-controlled study in which 132 dependent smokers abstained for 6 h with the assistance of either nicotine (2 mg, n?=?42 or 4 mg, n?=?24) or placebo (n?=?66) gum while travelling on a non-smoking train. Outcome measures were ratings of craving and mood withdrawal symptoms prior to treatment and at regular intervals during abstinence. RESULTS: In a multivariate analysis of all symptoms, there was no interaction between treatment and time [F(21,110)?=?1.28, p?=?0.20, [Formula: see text]?=?0.20] nor an effect of treatment [F(7,124)?=?0.45, p?=?0.87, [Formula: see text]?=?0.03]. There was an effect of time [F(21,110)?=?11.59, p?<?0.001, [Formula: see text]?=?0.69) and univariate analyses revealed that the majority of symptoms increased linearly throughout the period of abstinence with detectable onsets typically between the first 60 and 180 min of abstinence. CONCLUSIONS: Smokers who temporarily abstain in naturalistic settings experience craving and withdrawal symptoms that emerge linearly over the first 6 h of abstinence. Changes in craving and several mood withdrawal symptoms can be detected within the first 3 h. Nicotine gum may not have an acute effect on the development of these symptoms.

PMID: 23636302 [PubMed - as supplied by publisher]

Molecules and circuits involved in nicotine addiction: the many faces of smoking.

Neuropharmacology. 2013 Apr 27;

Authors: Picciotto MR, Mineur YS

Abstract
Tobacco smoking in humans is one of the most persistent and widespread addictions and is driven by nicotine in tobacco smoke. Over the last several decades, understanding of the molecular and cellular basis for nicotine addiction has increased tremendously as a result of pharmacological, molecular genetic, electrophysiological and behavioral studies of nicotine reinforcement. Studies of the biological basis for nicotine reinforcement has helped in the design of new treatments for smoking cessation such as varenicline; however, smokers report that they smoke for many reasons, including the ability to control symptoms of anxiety and depression or the desire to control appetite. Further, developmental exposure to tobacco smoke increases the likelihood of adult smoking. Here we review what is known about the molecular and circuit basis for a number of behaviors related to tobacco smoking. Leveraging the knowledge from studies of different behaviors mediated by nicotine receptors in multiple brain circuits could provide points of convergence that will inform future therapeutic development for smoking cessation.

PMID: 23632083 [PubMed - as supplied by publisher]

[Intervention and assistance by doctor for smoking cessation].

Nihon Rinsho. 2013 Mar;71(3):506-10

Authors: Muramatsu H

Abstract
Patients with nicotine dependence require suitable intervention and assistance for smoking cessation. We should try to provide every patient with the appropriate way to quit smoking. I'm making the patient classification (motivation-confidence typing) with a questionnaire. When the patient has poor motivation, the motivational interviewing and intervention are required. If the patient has poor self-confidence, I will encourage him and admire his efforts. So varenicline significantly reduce smoking satisfaction, that I allow patients to smoke intentionally during two weeks after starting smoking cessation program. Smoking under the influence of varenicline may be useful to quit without regret.

PMID: 23631244 [PubMed - in process]

[Health insurance coverage for smoking cessation treatment in Japan: current status and future issues].

Nihon Rinsho. 2013 Mar;71(3):499-505

Authors: Nakamura M

Abstract
In Japan, nicotine dependence treatment service for outpatients at registered medical institutions has been started under health insurance coverage since 2006. The reimbursed treatment program consists of five treatment sessions over 12 week duration. Nicotine patch or varenicline can be prescribed under health insurance coverage during the treatment period. The surveys conducted in 2007 and 2009 have proved the effectiveness of the service. However, the accessibility and utilization of smoking cessation treatment are not sufficient, considering the fact that the percentage of smokers who underwent smoking cessation treatment in Japan remained low compared with other countries. Future challenges call for implementing effective measures to improve the accessibility and utilization of the service, while maintaining a satisfactory level of treatment quality.

PMID: 23631243 [PubMed - in process]

[On oral medications, especially varenicline].

Nihon Rinsho. 2013 Mar;71(3):487-92

Authors: Kurioka N

Abstract
Varenicline is an orally administered alpha4beta2 nicotinic acetylcholine receptor partial agonist. It has been widely used in smoking cessation therapy. It reduces craving and withdrawal symptoms during abstinence and lowers the reinforcing effects of nicotine. A third action of the drug is to blunt responses to smoking cues. Varenicline has higher abstinence rates than nicotine transdermal patches or bupropion. As serious neuro-psychiatric symptoms had been reported post market, including drowsiness, suicidal thoughts and suicide, clinicians are recommended to review the patient's psychiatric history and should monitor them for changes in mood and behavior when prescribing this medication. Studies on flexible dosing regimens, flexible quit dates, and an increased pre-quit medication period have indicated possible improvement to varenicline's effectiveness.

PMID: 23631241 [PubMed - in process]

Predictors of quit success in Belgian participants of a varenicline observational smoking cessation study.

Acta Clin Belg. 2013 Jan-Feb;68(1):37-42

Authors: Boudrez H, Hoengenaert JP, Nackaerts K, Messig M, Metcalfe M

Abstract
BACKGROUND: We evaluated efficacy, predictors of quitting success and the safety profile of varenicline for smoking cessation in the Belgian participants in an observational, "real world" study.
METHODS: In this post-hoc analysis of a prospective, observational, non-comparative study, participants were adult smokers who were motivated to quit and were prescribed varenicline in accordance with the recommendations of the European Summary of Product Characteristics. The 7-day point prevalence of abstinence at Weeks 12 and 24 was determined based on patient reporting, and these data were further analysed by time to first cigarette on waking and by the use of behavioural support. The safety profile of varenicline was also assessed.
RESULTS: Overall, 61.1% of participants (n= 226) successfully quit smoking by the end of Week 12. There was a significant association between abstinence and time to first cigarette on waking (Week 12: OR, 0.69 [95% CI, 0.50-0.94], p = 0.02; Week 24: OR, 0.70 [95% CI, 0.52-0.94], p=0.02) and the use of behavioural support (Week 12: OR, 6.18 [95% CI, 3.41-11.2], p<0.01; Week 24: OR, 5.37 [95% CI, 2.89-9.98], p<0.01). The most frequent treatment-emergent adverse event was nausea (9.3%).
CONCLUSIONS: In this post-hoc analysis, varenicline was an effective smoking cessation aid with an acceptable safety profile in real world clinical practice in Belgian smokers. Significant predictors of abstinence were time to first cigarette on waking and use of behavioural support.

PMID: 23627193 [PubMed - in process]

Developing and validating a human laboratory model to screen medications for smoking cessation.

Nicotine Tob Res. 2012 Nov;14(11):1362-71

Authors: McKee SA, Weinberger AH, Shi J, Tetrault J, Coppola S

Abstract
INTRODUCTION: To facilitate translational work in medications development for smoking cessation, we have developed a human laboratory analogue of smoking lapse behavior. Our paradigm models 2 critical features of smoking lapse: the ability to resist the first cigarette and subsequent ad libitum smoking. In this paper we present the results of 2 studies designed to develop and validate the effect of nicotine deprivation on smoking lapse behavior.
METHODS: Study 1 (n = 30) was designed to develop the model parameters by examining varying levels of nicotine deprivation (1, 6, and 18 hr; within-subject) and identifying optimum levels of monetary reinforcement to provide while modeling the ability to resist smoking. Study 2 was designed to validate the model by screening smoking cessation medications with known clinical efficacy. Subjects (n = 62) were randomized to either varenicline 2 mg/day, bupropion 300 mg/day, or placebo, and we then modeled their ability to resist smoking and subsequent ad libitum smoking.
RESULTS: In Study 1, increasing levels of nicotine deprivation and decreasing levels of monetary reinforcement decreased the ability to resist smoking. In Study 2, the lapse model was found to be sensitive to medication effects among smokers who demonstrated a pattern of heavy, uninterrupted, and automated smoking (i.e., smoked within 5 min of waking). Ratings of craving, mood, withdrawal, and subjective cigarette effects are presented as secondary outcomes with results mirroring clinical findings.
CONCLUSIONS: Our smoking lapse model demonstrates promise as a translational tool to screen novel smoking cessation medications. Next steps in this line of research will focus on evaluating predictive validity.

PMID: 22492085 [PubMed - indexed for MEDLINE]

Divergent Functional Effects of Sazetidine-A and Varenicline During Nicotine Withdrawal.

Neuropsychopharmacology. 2013 Apr 29;

Authors: Turner JR, Wilkinson D, Poole RL, Gould TJ, Carlson GC, Blendy JA

Abstract
Smoking is the largest preventable cause of death in the United States ADDIN EN.CITE <EndNote><Cite><Author>CDC</Author><Year>2007</Year><RecNum>286</RecNum><record><rec-number>286</rec-number><foreign-keys><key app="EN" db-id="epdr95affz2wsqeezr5pzrzofevvxxesexer">286</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>CDC</author></authors></contributors><titles><title>Cigarette smoking among adults--United States, 2006.</title><secondary-title>Morbid. Mortal. Wkly. Rep.</secondary-title></titles><periodical><full-title>Morbid. Mortal. Wkly. Rep.</full-title></periodical><pages>1157-61</pages><volume>56</volume><number>44</number><dates><year>2007</year></dates><urls></urls></record></Cite></EndNote>(CDC, 2007). Furthermore, a recent study found that less than 10% of quit attempts resulted in continuous abstinence for one yearADDIN EN.CITE ADDIN EN.CITE.DATA (Gonzales et al, 2006). With the introduction of pharmacotherapies like Chantix™ (varenicline), a selective ?4?2 nicotinic partial agonist, successful quit attempts have significantly increased. Therefore, novel subtype-specific nicotinic drugs, such as sazetidine-A, present a rich area for investigation of therapeutic potential in smoking cessation. The present studies examine the anxiety-related behavioral and functional effects of the nicotinic partial agonists varenicline and sazetidine-A during withdrawal from chronic nicotine in mice. Our studies indicate that ventral hippocampal-specific infusions of sazetidine-A, but not varenicline, are efficacious in reducing nicotine withdrawal-related anxiety-like phenotypes in the novelty-induced hypophagia (NIH) paradigm. To further investigate functional differences between these partial agonists, we utilized voltage-sensitive dye imaging (VSDi) in ventral hippocampal slices to determine the effects of sazetidine-A and varenicline in animals chronically treated with saline, nicotine, or undergoing 24?h withdrawal. These studies demonstrate a functional dissociation of varenicline and sazetidine-A on hippocampal network activity, which is directly related to previous drug exposure. Furthermore, the effects of the nicotinic partial agonists in VSDi assays are significantly correlated to their behavioral effects in the NIH test. These findings highlight the importance of drug history in understanding the mechanisms through which nicotinic compounds may be aiding smoking cessation in individuals experiencing withdrawal-associated anxiety.Neuropsychopharmacology accepted article preview online, 29 April 2013; doi:10.1038/npp.2013.105.

PMID: 23624742 [PubMed - as supplied by publisher]