Maher Karam-Hage

A Randomized Double-Blind Pilot Trial of Gabapentin Versus Placebo to Treat Alcohol Dependence and Comorbid Insomnia

BACKGROUND Insomnia and other sleep disturbances are common, persistent, and associated with relapse in alcohol-dependent patients. The purpose of this pilot study was to compare gabapentin versus placebo for the treatment of insomnia and prevention of relapse in alcohol-dependent patients. METHODS Twenty-one subjects, including 10 women who met study criteria for alcohol dependence and insomnia and expressed a desire to abstain from alcohol, were recruited to the study. During a 1 to 2 week placebo lead-in and screening phase, a complete medical history, physical exam, blood tests, urine drug test, and structured interviews were performed to determine eligibility and patterns of alcohol use and sleep. Insomnia due to intoxication or acute withdrawal, psychiatric or medical illness, medications, and other sleep disorders were ruled out. Subjects were then randomized to either placebo (n = 11) or gabapentin (n = 10) for 6 weeks and titrated over a 10-day period to 1,500 mg or 5 pills at bedtime. After a 4-day taper, subjects were reassessed 6 weeks after ending treatment. RESULTS Gabapentin significantly delayed the onset to heavy drinking, an effect which persisted for 6 weeks after treatment ended. Insomnia improved in both treatment groups during the medication phase, but gabapentin had no differential effects on sleep as measured by either subjective report or polysomnography. CONCLUSION Because gabapentin is a short-acting medication that was taken only at nighttime in this study, it may possibly exert a nocturnal effect that prevents relapse to heavy drinking by a physiological mechanism not measured in this pilot study.

Effects of Varenicline and Bupropion Sustained-Release Use Plus Intensive Smoking Cessation Counseling on Prolonged Abstinence From Smoking and on Depression, Negative Affect, and Other Symptoms of Nicotine Withdrawal

IMPORTANCE Given the actions of varenicline tartrate and bupropion hydrochloride sustained-release (SR) on neurobiological targets related to affect and reward, it is thought that the modulation of nicotine withdrawal symptoms may contribute to their effectiveness. OBJECTIVE To assess the relative efficacy of varenicline and bupropion SR plus intensive counseling on smoking cessation and emotional functioning. DESIGN AND SETTING Placebo-controlled randomized clinical trial at a university medical center. PARTICIPANTS In total, 294 community volunteers who wanted to quit smoking. INTERVENTIONS Twelve weeks of varenicline, bupropion SR, or placebo plus intensive smoking cessation counseling (10 sessions, for a total of approximately 240 minutes of counseling). MAIN OUTCOME MEASURES Prolonged abstinence from smoking and weekly measures of depression, negative affect, and other symptoms of nicotine withdrawal. RESULTS Significant differences were found in abstinence at the end of treatment and through the 3-month postquit follow-up visit, favoring both active medications compared with placebo. At the 6-month postquit follow-up visit, only the varenicline vs placebo comparison remained significant. Varenicline use was also associated with a generalized suppression of depression and reduced smoking reward compared with the other treatments, while both active medications improved concentration, reduced craving, and decreased negative affect and sadness compared with placebo, while having little effect (increase or decrease) on anxiety and anger. No differences were noted in self-reported rates of neuropsychiatric adverse events. CONCLUSIONS AND RELEVANCE In a community sample, varenicline exerts a robust and favorable effect on smoking cessation relative to placebo and may have a favorable (suppressive) effect on symptoms of depression and other affective measures, with no clear unfavorable effect on neuropsychiatric adverse events. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00507728.

Effects of an intensive depression-focused intervention for smoking cessation in pregnancy.

OBJECTIVE The objective of this study was to evaluate a depression-focused treatment for smoking cessation in pregnant women versus a time and contact health education control. We hypothesized that the depression-focused treatment would lead to improved abstinence and reduced depressive symptoms among women with high levels of depressive symptomatology. No significant main effects of treatment were hypothesized. METHOD Pregnant smokers (N = 257) were randomly assigned to a 10-week, intensive, depression-focused intervention (cognitive behavioral analysis system of psychotherapy; CBASP) or to a time and contact control focused on health and wellness (HW); both included equivalent amounts of behavioral and motivational smoking cessation counseling. Of the sample, 54% were African American, and 37% met criteria for major depression. Mean age was 25 years (SD = 5.9), and women averaged 19.5 weeks (SD = 8.5) gestation at study entry. We measured symptoms of depression using the Center for Epidemiological Studies-Depression Scale (Radloff, 1977). RESULTS At 6 months posttreatment, women with higher levels of baseline depressive symptoms treated with CBASP were abstinent significantly more often, F(1, 253) = 5.61, p = .02, and had less depression, F(1, 2620) = 10.49, p = .001, than those treated with HW; those with low baseline depression fared better in HW. Differences in abstinence were not retained at 6 months postpartum. CONCLUSIONS The results suggest that pregnant women with high levels of depressive symptoms may benefit from a depression-focused treatment in terms of improved abstinence and depressive symptoms, both of which could have a combined positive effect on maternal and child health.

Open pilot study of gabapentin versus trazodone to treat insomnia in alcoholic outpatients.

Alcohol‐dependent outpatients with persisting insomnia were treated with either gabapentin or trazodone. Patients were assessed at baseline and after 4–6 weeks on medication using the Sleep Problems Questionnaire (SPQ). Of 55 cases initially treated, 9% dropped out due to morning drowsiness. Of the remaining 50 cases, 34 were treated with gabapentin (mean dose ± SD = 888 ± 418 mg) at bedtime and 16 were treated with trazodone (105 ± 57 mg) at bedtime. Both groups improved significantly on the SPQ but the gabapentin group improved significantly more than the trazodone group. Controlled studies are warranted to replicate these findings.

Complications of radiotherapy in laryngopharyngeal cancer: Effects of a prospective smoking cessation program

Radiotherapy (XRT) is effective as the primary treatment modality for laryngopharyngeal cancer; however, complications of XRT can result in significant morbidity. Few previous studies have examined the effect of continued smoking on complications of XRT. The authors of this report hypothesized that patients with laryngopharyngeal cancer who successfully quit smoking would have fewer complications of primary XRT.

Modifying Residents' Professional Attitudes about Substance Abuse Treatment and Training

Some physicians have negative attitudes and beliefs towards patients with addiction. Moreover, few residents are inclined towards a subspecialty fellowship in addiction psychiatry. We aimed to determine if a one-day educational conference could facilitate attitudinal change among 52 general psychiatry residents. Significant changes (p < 0.05) in attitudes were reported following the conference, including enhanced beliefs that physicians can motivate their addicted patients to seek treatment and increased physician interest in pursuing advanced addiction training. A one-day educational intervention may be effective in improving professional attitudes toward addiction treatment by reinforcing previously acquired medical education. The duration of these changes remains to be determined.

Prequit fMRI Responses to Pleasant Cues and Cigarette-Related Cues Predict Smoking Cessation Outcome

INTRODUCTION The reasons that some smokers find it harder to quit than others are unclear. Understanding how individual differences predict smoking cessation outcomes may allow the development of more successful personalized treatments for nicotine dependence. Theoretical models suggest that drug users might be characterized by increased sensitivity to drug cues and by reduced sensitivity to nondrug-related natural rewards. We hypothesized that baseline differences in brain sensitivity to natural rewards and cigarette-related cues would predict the outcome of a smoking cessation attempt. METHODS Using functional magnetic resonance imaging, we recorded prequit brain responses to neutral, emotional (pleasant and unpleasant), and cigarette-related cues from 55 smokers interested in quitting. We then assessed smoking abstinence, mood, and nicotine withdrawal symptoms during the course of a smoking cessation attempt. RESULTS Using cluster analysis, we identified 2 groups of smokers who differed in their baseline responses to pleasant cues and cigarette-related cues in the posterior visual association areas, the dorsal striatum, and the medial and dorsolateral prefrontal cortex. Smokers who showed lower prequit levels of brain reactivity to pleasant stimuli than to cigarette-related cues were less likely to be abstinent 6 months after their quit attempt, and they had higher levels of negative affect during the course of the quit attempt. CONCLUSIONS Smokers with blunted brain responses to pleasant stimuli, relative to cigarette-related stimuli, had more difficulty quitting smoking. For these individuals, the lack of alternative forms of reinforcement when nicotine deprived might be an important factor underlying relapse. Normalizing these pathological neuroadaptations may help them achieve abstinence.

Tobacco use and cessation for cancer survivors: an overview for clinicians.

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The effect of mood, anxiety, and alcohol use disorders on smoking cessation in cancer patients

Smoking is highly prevalent in individuals with psychiatric disorders. The relationship between smoking and anxiety disorders has received less attention than that of depression and substance use disorders, despite the fact that anxiety disorders are the most common of mental illnesses across the globe. In this study, we investigated the relationship between psychiatric disorders, including anxiety, depression, alcohol abuse, and comorbid combinations of these primary Axis I disorders and smoking cessation, in a cohort of 1,425 cancer patients who were participating in a smoking cessation clinical program. Patients were followed prospectively and assessed for abstinence status at the end of treatment and at 6-month posttreatment. Treatment involved six to eight behavioral smoking cessation counseling sessions over a 12- to 16-week period, and up to 12 weeks of smoking cessation pharmacotherapy. We hypothesized that patients with current anxiety disorders as well as other psychiatric disorders would have lower smoking cessation rates than those with no psychiatric disorders. There were no differences in abstinence rates between patients with anxiety disorders and those with no psychiatric disorders at end of treatment or 6 months. Patients with major depression or alcohol abuse had lower cessation rates than patients with no psychiatric disorders at 6 months. Findings suggest that both major depression and alcohol abuse may adversely affect treatment outcome in cancer patients. However, these findings should be considered within the limitations of observational studies that involve comparisons between nonrandomly assigned groups.

“Meaningful use” provides a meaningful opportunity

The article by Warren et al in this issue of Cancer is timely,1 because the US government has recently put into place a specific mandate for hospitals and health professionals to electronically screen for tobacco use. This mandate is spelled out in what are referred to as “meaningful use” regulations requiring that certain information be entered into each patient’s electronic health record (EHR) and be available to patients and their providers.2 In this editorial, we provide a model for meeting the mandate that includes implementation of a comprehensive smoking (tobacco) cessation program for cancer patients and the supporting evidence base for doing so as an alternative to the minimal intervention approach discussed by Warren et al. We also discuss the importance of an institution-wide, automated system to identify and refer tobacco users to treatment within the context of implementing the meaningful use regulations for EHR as required by the Health Information Technology for Economic and Clinical Health (HITECH) Act. Here, we briefly describe the effect of the meaningful use regulations for EHR on tobacco screening, the importance of automatic referrals for cessation assistance, and the continuing importance of provider referral and involvement. We then briefly discuss the Roswell Park Cancer Institute cessation program and the use of a public health model of care, which emphasizes providing minimal levels of intervention, and compare it with a more comprehensive model of cessation that provides a level of care tailored to the individual needs of cancer patients.Within this context, we discuss evidence supporting the use of a comprehensive treatment strategy for cancer patients that includes pharmacotherapy. To illustrate our points, we describe the comprehensive cessation programused at The University of TexasMDAnderson Cancer Center.