David Kalman

Co-morbidity of smoking in patients with psychiatric and substance use disorders.

This article reviews cigarette smoking in patients with psychiatric disorders (PD) and substance use disorders (SUD). Rates of smoking are approximately 23% in the U.S. population but approximately two- to four-fold higher in patients with PD and SUD. Many remaining smokers have had repeated smoking cessation failures, possibly due to the presence of co-morbid PD and SUDs. There is modest, evidence-based support for effective treatment interventions for nicotine addiction in PD and SUD. Further research is needed to increase our understanding of nicotine addiction in PD and SUD and develop more effective treatment interventions.

Addressing tobacco use disorder in smokers in early remission from alcohol dependence: The case for integrating smoking cessation services in substance use disorder treatment programs

Despite the declining overall rate of cigarette smoking in the general population in the United States, the prevalence of smoking is estimated to be as high as 80% among treatment-seeking alcoholics. The serious adverse health effects of tobacco and heavy alcohol use are synergistic and recent evidence suggests that smoking slows the process of cognitive recovery following alcohol abstinence. In addition, substantial evidence shows that treatment for tobacco dependence does not jeopardize alcohol abstinence. In this paper, we focus on the impact and treatment implications of tobacco dependence among treatment-seeking alcoholics through a review of five areas of research. We begin with brief reviews of two areas of research: studies investigating the genetic and neurobiological vulnerability of comorbid tobacco and alcohol dependence and studies investigating the consequences of comorbid dependence on neurobiological and cognitive functioning. We then review literature on the effects of smoking cessation on drinking urges and alcohol use and the effectiveness of smoking cessation interventions with alcoholic smokers. Finally, we offer recommendations for research with an emphasis on clinical research for enhancing smoking cessation outcomes in this population.

Concurrent versus delayed smoking cessation treatment for persons in early alcohol recovery. A pilot study.

This pilot study investigated the efficacy of initiating a smoking cessation intervention early in inpatient treatment for alcohol dependence versus shortly after an inpatient stay. Thirty-six male smokers recruited from an inpatient substance abuse treatment program were randomly assigned to begin smoking cessation either two weeks (concurrent treatment) or six weeks (delayed treatment) after admission to the substance abuse program. Smoking cessation treatment involved three sessions of individual smoking cessation treatment plus eight weeks of transdermal nicotine replacement. Significantly fewer participants began the delayed treatment than the concurrent treatment. Few participants were smoking-abstinent at follow-up, and the timing of treatment onset did not have an impact on smoking outcome. Clinical trials with larger samples may be needed to better evaluate the efficacy of concurrent versus delayed treatment and to test the efficacy of more aggressive interventions with smokers in early alcohol recovery.

The subjective effects of nicotine: methodological issues, a review of experimental studies, and recommendations for future research.

This paper reviews findings from placebo-controlled human experimental studies of the effects of nicotine on subjective experience. Studies are grouped according to whether participants were smokers (significantly nicotine deprived, minimally nicotine deprived) or non-smokers. Within each category, studies are also grouped according to method of nicotine administration (e.g., smoked tobacco, nasal spray) and nicotine dose. This review of studies is preceded by a discussion of several methodological issues in studies of nicotine and mood. The principal findings of this review are: (1) there is a linear relationship between nicotine dose and measures of drug high (e.g., head rush, euphoria) in significantly nicotine-deprived smokers; (2) there appear to be few positive or negative main effects of nicotine on mood in minimally nicotine-deprived smokers; (3) nicotine has positive effects (e.g., increases head rush) and negative effects (e.g., increases tension) in non-smokers; (4) stronger effects of nicotine on mood emerge when individual difference variables (e.g., neuroticism) and situational contingencies (e.g., exposure to stressful stimuli) are examined. Additional studies with minimally nicotine-deprived smokers and non-smokers are needed to further specify the conditions under which nicotine affects mood and other subjective experience. The review concludes with a discussion of putative mechanisms that may mediate the interaction between nicotine and moderating variables on affect and with suggestions for future research.

Does Nicotine Do What we Think it Does? A Meta-Analytic Review of the Subjective Effects of Nicotine in Nasal Spray and Intravenous Studies with Smokers and Nonsmokers

We conducted a meta-analysis of placebo-controlled laboratory studies of the subjective effects of nicotine. A total of 15 studies (11 with nasal spray, four with intravenous administration) with smokers and six studies (all with nasal spray) with never-smokers were included. Studies of other routes of administration (e.g., smoked tobacco) were not included because of insufficient numbers of available effect sizes. Meta-analysis results indicated that nicotine increased vigor for smokers but increased fatigue for never-smokers. Nicotine increased head rush for both smokers and never-smokers. In studies of smokers only, nicotine also increased ratings of drug high and drug liking. Contrary to expectations, nicotine decreased relaxation and increased tension/jitteriness for both smokers and never-smokers. Dose-response relationships were most clearly observed for head rush and drug high. Considerable variability was found across studies for a given nicotine dose and route of administration. Implications of the current findings about the role of subjective effects in nicotine reinforcement and self-administration are discussed along with commentary on methodological issues and recommendations for future studies.

Effects of bupropion on simulated demand for cigarettes and the subjective effects of smoking

INTRODUCTION The biobehavioral mechanism(s) mediating bupropions efficacy are not well understood. Behavioral economic measures such as demand curves have proven useful in investigations of the reinforcing effects of drugs of abuse. Behavioral economic measures may also be used to measure the effect of pharmacotherapies on the reinforcing effects of drugs of abuse. METHODS The effects of bupropion on simulated demand for cigarettes were investigated in a placebo-controlled double-blind clinical trial. Participants reported the number of cigarettes they would purchase and consume in a single day at a range of prices. The effects of medication on the subjective effects of smoking were also explored. RESULTS Demand for cigarettes was well described by an exponential demand equation. Bupropion did not significantly decrease the maximum number of cigarettes that participants said they would smoke in a single day nor did it significantly alter the relation between price per cigarette and demand. Baseline demand elasticity did not predict smoking cessation, but changes in elasticity following 1 week of treatment did. Medication group had no effect on any subjective effects of smoking. DISCUSSION Bupropion had no significant effects on demand for cigarettes. The exponential demand equation, recently introduced in behavioral economics, proved amenable to human simulated demand and might be usefully employed in other pharmacotherapy studies as it provides a potentially useful measure of changes in the essential value of the drug as a reinforcer. Such changes may be useful in predicting the efficacy of medications designed to reduce drug consumption.

Twelve-week outcomes from an investigation of high-dose nicotine patch therapy for heavy smokers with a past history of alcohol dependence.

This study reports findings from an investigation of the efficacy of high-dose nicotine patch (NP) therapy for heavy smokers with a past history of alcohol dependence. One hundred thirty participants were randomly assigned to 42 mg or 21 mg of transdermal nicotine for 4 weeks, followed by an 8-week dose titration. Follow-up assessments were conducted at 4 and 12 weeks. Differences between dose conditions were nonsignificant, although unexpectedly, outcomes favored participants in the 21-mg NP condition. Nicotine abstinence at follow-up was related to longer length of alcohol abstinence at time of enrollment. Future research should investigate ways to improve smoking quit rates in this population, including more frequent counseling sessions and/or other pharmacotherapies. These investigations should focus primarily on smokers in early alcohol recovery.

Predictors of Relapse in a Bupropion Trial for Smoking Cessation in Recently-Abstinent Alcoholics: Preliminary Results Using an Aggregate Genetic Risk Score

Introduction Rates of smoking in the US population have decreased overall, but rates in some groups, including alcoholic smokers, remain high. Many newly sober alcoholics are concerned about their smoking and some attempt to quit. However, quit rates in this population are low. Prior studies suggest risk for relapse in this population may be genetically influenced and that genetic factors may moderate response to treatment. Methods In this exploratory study, we had two specific aims: (1) to investigate associations between genetic risk and outcome; (2) to investigate whether genetic risk moderates the efficacy of a medication intervention. Data are from a subsample of 90 participants from a clinical trial of smoking cessation treatment for smokers with between 2 and 12 months of alcohol abstinence. Subjects were randomly assigned to bupropion or placebo. All subjects received counseling and nicotine patches. To examine the possibility that bupropion may have been efficacious in participants with a specific genetic profile (ie, a pharmacogenetic approach), an aggregate genetic risk score was created by combining risk genotypes previously identified in bupropion treatment studies. Results Although medication efficacy was not moderated by the aggregate genetic risk score, there was an interaction between nicotine dependence and genetic risk in predicting smoking abstinence rates at the end of treatment (10 weeks). Conclusions Results suggest an aggregate genetic risk score approach may have utility in treatment trials of alcoholics who smoke. Additionally, these findings suggest a strategy for understanding and interpreting conflicting results for single genetic markers examined as moderators of smoking cessation treatment.

Do poor health behaviors affect health-related quality of life and healthcare utilization among veterans? The Veterans Health Study.

The impact of health behaviors on Health-Related Quality of Life (HRQoL) and HealthCare Utilization (HCU) was examined in a sample of male veterans. We examined the relationship between health behaviors (cigarette smoking, alcohol use, exercise, seat belt use, cholesterol level, and body mass index [BMI]), and HRQoL and HCU, among Veterans Health Study participants providing complete baseline (t0) and 12-month follow-up (t12) data. (Respective sample sizes were 1242 and 1397.) HRQoL measures were derived from the SF-36, expressed as physical component summary (PCS) and mental component summary (MCS) scores. Prospective 12-month outpatient and inpatient utilization data were obtained from a VA administrative database. Exercise and BMI were significant PCS predictors at t0 and t12, adjusting for age, social supports, education, employment status, and comorbidities. Smoker status was negatively associated with PCS only at t0. Nonproblem (no abuse) alcohol users had significantly higher t0 PCS scores than nonusers. Only current problem alcohol use was associated with lower MCS at t0 and t12 in multivariate analyses. Regarding HCU, current smokers had fewer medical visits than never smokers; alcohol nonusers had more medical visits than current alcohol users, current problem users, and former problem users. No behaviors were associated with mental health visits or inpatient stays. HRQoL is negatively affected by poor health behaviors. HRQoL and physical health may be improved by practitioners targeting these behaviors for preventive interventions. This study did not support an association between poor health behaviors and higher HCU. Future research should consider the effect of moderating variables on this relationship.

Telephone Smoking-Cessation Counseling for Smokers in Mental Health Clinics: A Patient-Randomized Controlled Trial.

INTRODUCTION People with a mental health diagnosis have high rates of tobacco use and encounter limited availability of tobacco treatment targeted to their needs. This study compared the effectiveness of a specialized telephone smoking-cessation intervention developed for mental health patients with standard state quit-line counseling. DESIGN RCT. SETTING/PARTICIPANTS The study was conducted at six Veterans Health Administration facilities in the Northeast U.S. Participants were 577 mental health clinic patients referred by their providers for smoking-cessation treatment. INTERVENTION From 2010 to 2012, the study implemented a telephone program that included patient referral from a mental health provider, mailed cessation medications, and telephone counseling. Participants were randomized to receive a specialized multisession telephone counseling protocol (n=270) or transfer to their states quit-line for counseling (n=307). MAIN OUTCOME MEASURES Participants completed telephone surveys at baseline, 2 months, and 6 months. The studys primary outcome was self-reported 30-day abstinence at 6 months. Secondary outcomes were self-reported 30-day abstinence, counseling satisfaction and counseling content at 2 months, and self-reported use of cessation treatment and quit attempts at 6 months. Logistic regression was used to compare treatment groups on outcomes, controlling for baseline cigarettes per day and site. Inverse probability weighting and multiple imputation were used to handle missing abstinence outcomes. Data were analyzed in 2014-2015. RESULTS At 6 months, participants in the specialized counseling arm were more likely to report 30-day abstinence (26% vs 18%, OR=1.62, 95% CI=1.24, 2.11). There was no significant group difference in abstinence at 2 months (18% vs 14%, OR=1.31, 95% CI=0.49, 3.49). Participants in the specialized arm were more likely to be assisted with developing a quit plan; receive follow-up calls after quitting; and receive counseling on several domains, including motivation, confidence, smoking triggers, coping with urges, and mental health symptoms (all p<0.05). Specialized counseling participants were more satisfied with treatment and more likely to find the counseling useful (p<0.05). CONCLUSIONS The specialized counseling intervention was more effective at helping patients quit than transfer to a state quit-line. Patients were more satisfied with the specialized counseling program. TRIAL REGISTRATION This study is registered at www.clinicaltrials.gov NCT00724308.