Effects of Varenicline, Bupropion, Nicotine Patch, and Placebo on Treating Smoking Among Persons With Current or Past Major Depressive Disorder: Secondary Analysis of a Double-Blind, Randomized, Placebo-Controlled Trial.

Objective: The aim of this study was to compare the safety and efficacy of the leading smoking cessation medications among individuals with current versus past major depressive disorder (MDD).

Methods: This was a secondary analysis of a randomized, double-blind trial over 12 weeks with varenicline or bupropion, followed by a 12-week assessment, in participants ages 18-75 with past (N=2,174) or current (N=451) MDD or without psychiatric disorders (N=4,028). Interventions included 12 weeks of pharmacotherapy with placebo, nicotine replacement therapy (NRT; nicotine patch), bupropion, or varenicline, and brief counseling.

Do tobacco regulatory and economic factors influence smoking cessation outcomes? A post-hoc analysis of the multinational EAGLES randomised controlled trial.

Introduction: We previously reported global regional differences in smoking cessation outcomes, with smokers of US origin having lower quit rates than smokers from some other countries. This post-hoc analysis examined global regional differences in individual-level and country-level epidemiological, economic and tobacco regulatory factors that may affect cessation outcomes.

Methods: EAGLES (Evaluating Adverse Events in a Global Smoking Cessation Study) was a randomised controlled trial that evaluated first-line cessation medications and placebo in 8144 smokers with and without psychiatric disorders from 16 countries across seven regions.

Sex differences in alcohol's effects on fronto-amygdalar functional connectivity during processing of emotional stimuli.

Background: Amygdala function underlying emotion processing has been shown to vary with an individuals' biological sex. Expanding upon functional magnetic resonance imaging (fMRI) findings reported previously where a low level of response was the focus, we examined alcohol and sex effects on functional connectivity between the amygdala and other brain regions. The central hypothesis predicted that sex would influence alcohol's effects on frontal-limbic functional circuits underlying the processing of negative and positive facial emotions.

Combining varenicline preloading with Acceptance and Commitment Therapy (ACT) in persons with serious mental illness who smoke: The randomized ACTSLow pilot feasibility trial.

Background: People with serious mental illness (SMI; bipolar [BD] or schizophrenia spectrum disorders [SSD]) who smoke have 30-60% lower odds of quitting and are more prone to experience neuropsychiatric adverse events (NPSAEs) when quitting than smokers without SMI. We pilot-tested the feasibility of combining two different dosing strategies of varenicline preloading with Acceptance and Commitment Therapy (ACT) in persons with SMI in an attempt to bolster quit rates without increasing NPSAEs.

Methods: Twelve-week, single center, randomized, double-blind, pilot feasibility trial of low (0.

Sex effects in predictors of smoking abstinence and neuropsychiatric adverse events in the EAGLES trial.

Unlabelled: Significance There are sex effects in abstinence outcomes across all smoking cessation medications, but there is limited information regarding sex effects on cessation-related neuropsychiatric adverse events (NPSAEs) or interactions with psychiatric status.

Methods: Secondary analysis of data from EAGLES of 8144 adults who smoke cigarettes randomized to varenicline, bupropion, nicotine patch or placebo. Design characteristics included region (within/outside US), psychiatric cohort (absent/present), and treatment.

The effects of varenicline, bupropion, nicotine patch, and placebo on smoking cessation among smokers with major depression: A randomized clinical trial.

Importance: Improving treatment outcomes for smokers with major depressive disorder (MDD) can have significant public health implications.

Objective: To evaluate the safety and efficacy of smoking cessation pharmacotherapy among smokers with MDD.

Design: Secondary analysis of a randomized, double-blind, active- (nicotine patch) and placebo-controlled trial of 12 weeks of either varenicline or bupropion with a 12-week follow-up.

Topiramate decreases the salience of motivationally relevant visual cues among smokers with alcohol use disorder.

Background: There is preliminary evidence that the anticonvulsant topiramate increases the likelihood of both smoking and alcohol abstinence among smokers with alcohol use disorder (AUD), but its therapeutic mechanism has not been determined. We used event-related potentials (ERPs) to evaluate topiramate's effect on the salience of drug-related, emotional, and neutral pictorial cues to identify whether one of its potential therapeutic mechanisms involves reduction of the salience of motivationally relevant cues.

Methods: Participants enrolled in a multisite clinical trial treating smokers with AUD were randomly assigned to receive placebo, low-dose topiramate (up to 125 mg/day), or high-dose topiramate (up to 250 mg/day), along with brief behavioral compliance enhancement treatment.

Behavioral Economic Assessment of Alcohol and Cigarette Demand in Smokers With Alcohol Use Disorder.

Behavioral economic purchase tasks are widely used to assess drug demand in substance use disorder research. Comorbid alcohol use is common among cigarette smokers and associated with greater difficulty in quitting smoking. However, demand for alcohol and cigarettes in this population has not been fully characterized.

Relationship between level of response to alcohol and acute tolerance.

Background: A low level of response (low LR) to alcohol correlates with the later development of alcohol-related problems. Although some of the underpinnings of LR are understood, little is known about the potential relationship between LR and acute tolerance. The current analyses tested the hypothesis that a low LR will be explained in part by more intense acute tolerance to alcohol during a drinking session.

Estimation of risk of neuropsychiatric adverse events from varenicline, bupropion and nicotine patch versus placebo: secondary analysis of results from the EAGLES trial using Bayes factors.

Background And Aims: Analysed using classical frequentist hypothesis testing with alpha set to 0.05, the Evaluating Adverse Events in a Global Smoking Cessation Study (EAGLES) did not find enough evidence to reject the hypothesis of no difference in neuropsychiatric adverse events (NPSAEs) attributable to varenicline, bupropion, or nicotine patch compared with placebo. This might be because the null hypothesis was true or because the data were insensitive.

Psychiatric Comorbidity and Multimorbidity in the EAGLES Trial: Descriptive Correlates and Associations With Neuropsychiatric Adverse Events, Treatment Adherence, and Smoking Cessation.

Introduction: Psychiatric and substance use disorders represent barriers to smoking cessation. We sought to identify correlates of psychiatric comorbidity (CM; 2 diagnoses) and multimorbidity (MM; 3+ diagnoses) among smokers attempting to quit and to evaluate whether these conditions predicted neuropsychiatric adverse events (NPSAEs), treatment adherence, or cessation efficacy (CE).

Aims And Methods: Data were collected from November 2011 to January 2015 across sixteen countries and reflect the psychiatric cohort of the EAGLES trial.

Efficacy and Safety of Pharmacotherapeutic Smoking Cessation Aids in Schizophrenia Spectrum Disorders: Subgroup Analysis of EAGLES.

Objective: This study aimed to evaluate the efficacy and safety of varenicline, bupropion, and nicotine replacement therapy (NRT) among smokers with schizophrenia spectrum disorders in post hoc analyses of Evaluating Adverse Events in a Global Smoking Cessation Study data.

Methods: Smokers with schizophrenia spectrum disorder (N=390) and without a psychiatric illness (control group, N=4,028) were randomly assigned to receive varenicline, bupropion, NRT patch, or placebo for 12 weeks. Outcomes included abstinence rates during treatment and follow-up, number needed to treat (NNT) for abstinence, incidence of neuropsychiatric adverse events (NPSAEs), and temporal relationship between NPSAEs and abstinence status.

Efficacy and safety of pharmacotherapies for smoking cessation in anxiety disorders: Subgroup analysis of the randomized, active- and placebo-controlled EAGLES trial.

Background: Smoking rates are high in adults with anxiety disorders (ADs), yet little is known about the safety and efficacy of smoking-cessation pharmacotherapies in this group.

Methods: Post hoc analyses in 712 smokers with AD (posttraumatic stress disorder [PTSD], n = 192; generalized anxiety disorder [GAD], n = 243; panic disorder [PD], n = 277) and in a nonpsychiatric cohort (NPC; n = 4,028). Participants were randomly assigned to varenicline, bupropion, nicotine-replacement therapy (NRT), or placebo plus weekly smoking-cessation counseling for 12 weeks, with 12 weeks follow-up.

Safety and efficacy of first-line smoking cessation pharmacotherapies in bipolar disorders: Subgroup analysis of a randomized clinical trial.

Objectives: Post hoc analyses of EAGLES data to examine safety and efficacy of first-line smoking cessation pharmacotherapies in smokers with bipolar disorders (BD).

Methods: Smokers with BD I/II (n = 285; 81.4% with BD I) and a comparison nonpsychiatric cohort (NPC; n = 2794) were randomly assigned to varenicline, bupropion, nicotine replacement therapy (NRT), or placebo for 12 weeks, plus weekly counseling.

Predictors of Neuropsychiatric Adverse Events with Smoking Cessation Medications in the Randomized Controlled EAGLES Trial.

Background: Pre-treatment factors that increase smokers' risk of experiencing neuropsychiatric adverse events (NPSAEs) when quitting smoking are unknown.

Objective: To identify baseline smoker characteristics beyond the history of mental illness that predict which participants were more likely to experience moderate to severe NPSAEs in EAGLES.

Design: A prospective correlational cohort study in the context of a multinational, multicenter, double-blind, randomized trial.

Neuropsychiatric Safety and Efficacy of Varenicline, Bupropion, and Nicotine Patch in Smokers With Psychotic, Anxiety, and Mood Disorders in the EAGLES Trial.

Background: Neuropsychiatric safety and relative efficacy of varenicline, bupropion, and transdermal nicotine patch (NRT) in those with psychiatric disorders are of interest.

Methods: We performed secondary analyses of safety and efficacy outcomes by psychiatric diagnosis in EAGLES (Evaluating Adverse Events in a Global Smoking Cessation Study), a 12-week, randomized, double-blind, triple-dummy, placebo- and active (NRT)-controlled trial of varenicline and bupropion with 12-week follow-up, in a subset population, n = 4092, with a primary psychotic (n = 390), anxiety (n = 792), or mood (n = 2910) disorder. Primary end-point parameters were incidence of prespecified moderate and severe neuropsychiatric adverse events (NPSAEs) and weeks 9 to 12 continuous abstinence rates (9-12CAR).

Predictors of reduced smoking quantity among recovering alcohol dependent men in a smoking cessation trial.

Introduction: Adults with alcohol dependence (AD) have exceptionally high smoking rates and poor smoking cessation outcomes. Discovery of factors that predict reduced smoking among AD smokers may help improve treatment. This study examined baseline predictors of smoking quantity among AD smokers in a pharmacotherapy trial for smoking cessation.

Sex differences in the ACTH and cortisol response to pharmacological probes are stressor-specific and occur regardless of alcohol dependence history.

Women and men differ in their risk for developing stress-related conditions such as alcohol use and anxiety disorders and there are gender differences in the typical sequence in which these disorders co-occur. However, the neural systems underlying these gender-biased psychopathologies and clinical course modifiers in humans are poorly understood and may involve both central and peripheral mechanisms regulating the limbic-hypothalamic-pituitary-adrenal axis. In the present randomized, double blind, placebo-controlled, triple-dummy crossover study, we juxtaposed a centrally-acting, citalopram (2 mg/unit BMI) neuroendocrine stimulation test with a peripherally-acting, dexamethasone (Dex) (1.

Cardiovascular Safety of Varenicline, Bupropion, and Nicotine Patch in Smokers: A Randomized Clinical Trial.

Importance: Quitting smoking is enhanced by the use of pharmacotherapies, but concerns have been raised regarding the cardiovascular safety of such medications.

Objective: To compare the relative cardiovascular safety risk of smoking cessation treatments.

Design, Setting, And Participants: A double-blind, randomized, triple-dummy, placebo- and active-controlled trial (Evaluating Adverse Events in a Global Smoking Cessation Study [EAGLES]) and its nontreatment extension trial was conducted at 140 multinational centers.

Factors associated with the efficacy of smoking cessation treatments and predictors of smoking abstinence in EAGLES.

Aims: To assess (1) how far the efficacies of front-line smoking cessation pharmacotherapies vary as a function of smoker characteristics and (2) associations between these characteristics and success of smoking cessation attempts.

Design: Prospective correlational study in the context of a double-blind randomized trial. The outcome was regressed individually onto each covariate after adjusting for treatment, and then a forward stepwise model constructed.

Effects of Varenicline, Depressive Symptoms, and Region of Enrollment on Smoking Cessation in Depressed Smokers.

Introduction: Despite effective treatments, relapse to smoking remains a vexing global health problem. One predictor of relapse is depressive symptoms. Medications such as varenicline reduce withdrawal-related symptoms of depression, reducing relapse.

"I Smoke Like This to Suppress These Issues That Are Flaws of My Character": Challenges and Facilitators of Cessation Among Smokers With Bipolar Disorder.

Objective: Smokers with bipolar disorder (BD) have low rates of successful quitting, yet no prior studies have evaluated the process of quitting among these smokers in the context of a current quit attempt. To facilitate development of more effective interventions, we conducted a qualitative exploration of challenges and facilitators of quitting in an intervention study for smokers with BD.

Methods: Participants were adult daily smokers with BD (n = 10) who completed a 10-week smoking cessation intervention consisting of Acceptance and Commitment Therapy (ACT) and nicotine patch.

Metabotropic Glutamate Receptors 2 and 3 as Targets for Treating Nicotine Addiction.

Tobacco smoking, driven by the addictive properties of nicotine, continues to be a worldwide health problem. Based on the well-established role of glutamatergic neurotransmission in drug addiction, novel medication development strategies seek to halt nicotine consumption and prevent relapse to tobacco smoking by modulating glutamate transmission. The presynaptic inhibitory metabotropic glutamate receptors 2 and 3 (mGluR2/3) are key autoreceptors on glutamatergic terminals that maintain glutamate homeostasis.