Daily ratings measures of alcohol craving during an inpatient stay define subtypes of alcohol addiction that predict subsequent risk for resumption of drinking

Background

Both depressive symptoms and alcohol craving have been postulated as important predictors of relapse in patients with addictive disorders. The purpose of this study was to examine the course of affective symptoms and cravings for alcohol use during the initial 25 days of residential treatment for middle aged and older adults addicted to alcohol and the relationship between these symptoms and recovery outcomes.

Methods

95 alcohol-dependent subjects were enrolled in this observational study. Participants completed a daily diary of alcohol craving, positive affect, and negative affect during residential treatment. Participants were interviewed 1 and 6 months after discharge to assess clinical symptoms of relapse and functioning.

Results

Latent class analysis identified three groups of individuals for each of the three daily measures. For alcohol craving, 17 subjects reported elevated cravings during the entire treatment stay, 37 subjects reported initially elevated but then a slight improvement in craving, and 41 subjects reported relatively low craving from the time of admission to the end of residential treatment. Alcohol craving class was associated with negative affect but not positive affect. Alcohol craving class but not affective class was predictive of time to relapse to any drinking in the 6 months after residential treatment (p < 0.05).

Conclusion

Results suggest that non-cue induced alcohol craving may define a subtype of alcohol dependence that is less responsive to treatment and may explain heterogeneity in treatment outcomes. These results also may suggest a role for differential treatment programming to address high states of craving for alcohol.     

A double-blind,placebo-controlled trial of topiramate for the treatment of comorbid cocaine and alcohol dependence

Background

Topiramate increases GABAergic activity and antagonizes the AMPA/kainate subtype of glutamate receptors. Through these mechanisms of action, topiramate may reduce alcohol and cocaine reward and may reduce alcohol and cocaine craving. Topiramate has been shown to reduce drinking in persons with alcohol dependence, and reduce relapse in stimulant-dependent patients. The current trial was intended to test the ability of topiramate to promote cocaine and alcohol abstinence among patients addicted to both drugs.

Methods

The study was a double-blind, placebo-controlled, 13-week trial involving 170 cocaine and alcohol dependent subjects. After achieving a period of cocaine and alcohol abstinence, subjects were randomized to topiramate, 300 mg daily, or identical placebo capsules. In addition, subjects received weekly individual psychotherapy. Primary outcome measures included self-reported alcohol and cocaine use, and thrice weekly urine drug screens. Secondary outcome measures included cocaine and alcohol craving, Addiction Severity Index results, cocaine withdrawal symptoms, and clinical global improvement ratings.

Results

Topiramate was not better than placebo in reducing cocaine use on the a priori primary outcome measure, or in reducing alcohol use. Topiramate was not better than placebo in reducing cocaine craving. Topiramate-treated subjects, compared to placebo-treated subjects, were more likely to be retained in treatment and more likely to be abstinent from cocaine during the last three weeks of the trial. Subjects who entered treatment with more severe cocaine withdrawal symptoms responded better to topiramate.

Discussion

Topiramate plus cognitive behavioral therapy may reduce cocaine use for some patients with comorbid cocaine and alcohol dependence.     

Tobacco dependence treatment for hospitalized smokers: a randomized, controlled, pilot trial using varenicline

Objective

The hospital can be an important opportunity for smoking cessation interventions. This is the first randomized, double-blinded, placebo-controlled pilot trial utilizing varenicline and post-discharge, in-person behavioral treatment for hospitalized smokers.

Method

Seventy-nine smokers admitted to a university-based hospital with various diagnoses were enrolled from 2007 to 2009. The primary outcome was biochemically confirmed abstinence at 24 weeks following discharge. Secondary outcomes included withdrawal symptoms, motivation, utilization of treatment, and medical events.

Results

Overall abstinence at 24 weeks was 27% with no difference between varenicline and placebo treatment groups (23% vs. 31%). There were no significant differences in motivation to stop smoking or withdrawal symptoms. Over 40% of all subjects utilized post-discharge behavioral treatment with significantly higher abstinence rates compared with those who did not (53.1% vs. 8.5%, p < 0.01). Overall adverse events were similar in both treatment groups with the only significant difference being more nausea in the varenicline group (25% vs. 5%; p < 0.01). Twenty-three subjects were re-hospitalized with no significant differences between treatment groups (13 varenicline vs. 10 placebo).

Conclusion

This pilot trial of varenicline in hospitalized smokers demonstrated feasibility of implementation, produced some hypothesis-generating findings, and suggested the potential benefit of face-to-face treatment following discharge.     

Varenicline effects on drinking,craving and neural reward processing among non-treatment-seeking alcohol-dependent individuals

Rationale

The α4β2 nicotinic acetylcholine receptor partial agonist varenicline has been reported to reduce drinking among both heavy-drinking smokers and primary alcoholics, and this effect may be related to varenicline-mediated reduction of alcohol craving. Among smokers, varenicline has been reported to modulate cigarette cue-elicited brain activation in several reward-related areas.

Objectives

This pilot study tested varenicline’s effects on drinking, alcohol craving, and alcohol cue-elicited activation of reward-related brain areas among non-treatment-seeking alcohol-dependent individuals.

Methods

Thirty-five such individuals (mean age?=?30, 57 % male, 76 % heavy drinking days in the past month, 15 smokers) were randomized to either varenicline (titrated to 2 mg) or placebo for 14 days, and were administered an alcohol cue reactivity fMRI task on day 14. A priori regions of interest (ROIs) were bilateral and medial orbitofrontal cortex (OFC), right ventral striatum (VS), and medial prefrontal cortex (mPFC).

Results

Despite good medication adherence, varenicline did not reduce heavy drinking days or other drinking parameters. It did, however, increase self-reported control over alcohol-related thoughts and reduced cue-elicited activation bilaterally in the OFC, but not in other brain areas.

Conclusions

These data indicate that varenicline reduces alcohol craving and some of the neural substrates of alcohol cue reactivity. However, varenicline effects on drinking mediated by cue-elicited brain activation and craving might be best observed among treatment-seekers motivated to reduce their alcohol consumption.     

Symptoms of alcohol dependence and smoking initiation and persistence: A longitudinal study among US adults

Background

A large number of adults report symptoms of, but do not meet diagnostic criteria for, an alcohol use disorder. Yet, little is known about the relationship between symptoms of alcohol use disorders and the initiation and persistence of smoking. This study prospectively examines the relationship between having 1–2 symptoms of alcohol dependence (without abuse) and smoking initiation and persistence as well as nicotine dependence over a 3-year period among adults in the United States.

Methods

Data were drawn from Wave 1 (2001–2002) and Wave 2 (2004–2005) of the National Epidemiologic Survey on Alcohol and Related Conditions. Relationships between Wave 1 symptoms of alcohol dependence, alcohol abuse, and alcohol dependence and initiation and persistence of cigarette smoking and nicotine dependence at Wave 2 were examined using logistic regression analyses. Analyses were adjusted for demographics, mood and anxiety disorders.

Results

Symptoms of alcohol dependence were associated with smoking initiation at Wave 2. There was no association between symptoms of alcohol dependence and smoking persistence. Symptoms of alcohol dependence predicted incident and persistent nicotine dependence. Findings persisted after adjusting for demographic characteristics and mood/anxiety disorders.

Conclusions

Even 1–2 symptoms of alcohol dependence are associated with increased vulnerability to smoking initiation and onset and persistence of nicotine dependence at a similar strength as alcohol use disorders. Efforts at smoking cessation must address problematic alcohol use, even at the subclinical level, in order to improve efficacy.     

Effects of Varenicline on Neural Correlates of Alcohol Salience in Heavy Drinkers

Background:

Preclinical and emerging clinical evidence indicates that varenicline, a nicotinic partial agonist approved for smoking cessation, attenuates alcohol seeking and consumption. Reductions of alcohol craving have been observed under varenicline treatment and suggest effects of the medication on alcohol reward processing, but this hypothesis remains untested.

Methods:

In this double-blind, placebo-controlled randomized experimental medicine study, 29 heavy drinkers underwent a functional magnetic resonance imaging scan after 2 weeks of varenicline (2mg/d) or placebo administration. During functional magnetic resonance imaging, participants performed the Alcohol-Food Incentive Delay task, where they could earn points for snacks or alcohol. At baseline and after 3 weeks of medication, participants underwent intravenous alcohol self-administration sessions in the laboratory.

Results:

During the functional magnetic resonance imaging scan, participants in the varenicline group (N=17) reported lower feelings of happiness and excitement on subjective mood scales when anticipating alcohol reward compared with the placebo group (N=12). Linear mixed effects analysis revealed that anticipation of alcohol reward was associated with significant blood oxygen level dependent activation of the ventral striatum, amygdala, and posterior insula in the placebo group; this activation was attenuated in the varenicline group. The varenicline group showed no difference in intravenous alcohol self-administration relative to the placebo group for either session. Participants with higher insula activation when anticipating alcohol reward showed higher alcohol self-administration behavior across groups.

Conclusions:

Our findings suggest that varenicline decreases blood oxygen level dependent activation in striato-cortico-limbic regions associated with motivation and incentive salience of alcohol in heavy drinkers. This mechanism may underlie the clinical effectiveness of varenicline in reducing alcohol intake and indicates its potential utility as a pharmacotherapy for alcohol use disorders.     

Effects of acute combined serotonin and dopamine depletion on cue-induced drinking intention/desire and cognitive function in patients with alcohol dependence

Background

Alcohol cues can precipitate the desire to drink and cause relapse in recovering alcohol-dependent patients. Serotonin and dopamine may play a role in alcohol cue-induced craving. Acute combined tryptophan (Trp), tyrosine (Tyr), and phenylalanine (Phe) depletion (CMD) in the diet attenuates the synthesis of serotonin and dopamine in the human brain. However, no study of the effects of acute CMD has been previously conducted. Therefore, we investigated whether the attenuation of serotonin and dopamine synthesis changes cue-induced alcohol craving in recently abstinent alcoholics.

Methods

In this double-blind, randomized, placebo-controlled, crossover design, 12 male patients who met the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, criteria for alcohol dependence were divided into two conditions: (1) monoamine depletion (i.e., consumption of a concentrated amino acid beverage that resulted in a rapid and significant decrease in plasma-free Tyr/Phe/Trp) and (2) balanced condition (i.e., consumption of a similar beverage that contained Tyr/Phe/Trp). The participants were scheduled for two experimental sessions, with an interval of ≥7 days. The cue-induced craving test session was conducted 6 h after each amino acid beverage administration. Drinking urge, blood pressure, heart rate, working memory, and attention/psychomotor performance were assessed before and after administration.

Results

Compared with the balanced condition, the monoamine depletion condition significantly increased drinking intention/desire and diastolic blood pressure. Cognitive performance was not different between the two conditions.

Conclusions

Acute combined serotonin and dopamine depletion may increase drinking intention/desire and diastolic blood pressure without influencing cognitive function.     

Alcohol use as a signal for sensitivity to nicotine dependence among recent onset smokers

Objective

This study evaluated the association between alcohol use, abuse and dependence and cigarette smoking to determine whether alcohol may signal greater sensitivity to nicotine dependence at very low levels of smoking.

Method

Data were drawn from five annual National Surveys on Drug Use and Health and included individuals age 12 to 21 who reported first exposure to smoking within the past two years and smoking at least once in the past month.

Results

Both alcohol abuse and alcohol dependence were associated with increased likelihood of symptoms that seem to tap tolerance for nicotine. These included items such as “the amount you smoke has increased”; “needing to smoke a lot more now in order to be satisfied”; and “smoking much more before starting to feel anything”. Alcohol dependence, but not abuse was associated with the remaining symptoms, “after not smoking for a while, needing to smoke to feel less restless and irritable”; “craving cigarettes after not smoking for a while”; and “worrying about running out of cigarettes”. All associations were not better accounted for by either alcohol use or amount smoked.

Conclusion

If causally associated, treatment of alcohol-use disorders may prevent or reduce the early emergence of nicotine dependence symptoms among new smokers, very early in the smoking uptake process. If instead alcohol disorders are a signal of sensitivity for nicotine dependence best accounted for by a third variable, then adolescents with alcohol dependence and/or abuse during early exposures to smoking represents an important subgroup that may benefit from interventions directly targeting this association.     

The influence of depressed mood on action tendencies toward alcohol: The moderational role of drinking motives

Background

Research suggests that depressed mood is associated with alcohol-related problems, though its relation with drinking behavior has been inconsistent across studies. Efforts to better understand the link between depressed mood and alcohol use have examined drinking motives as a potentially important moderating variable. The current study sought to examine whether drinking motives moderate the influence of depressed mood on alcohol-related action tendencies. Based on Baker, Morse, and Sherman's (1986) positive and negative reinforcement schema model, two competing moderational hypotheses regarding the influence of depressed mood on appetitive responses for alcohol were tested.

Methods

One hundred and sixty-nine college student drinkers completed assessments of drinking motives and alcohol use. Subjects were exposed to a neutral or depressed mood induction followed by a computerized measure of action tendencies toward alcohol stimuli.

Results

Hierarchical regression analyses were conducted to examine whether the influence of depressed mood on action tendencies toward alcohol was moderated by drinking motives. Results showed that there was a significant interaction between mood induction condition and enhancement motives, such that depressed mood appeared to suppress appetitive responding toward alcohol among those with higher enhancement motives. In contrast, there was no evidence that coping motives moderated the association between mood and appetitive response to alcohol.

Conclusions

These results suggest that inhibiting affect states associated with one's motivational disposition for drinking may result in the devaluation of alcohol. Limitations and implications are discussed.     

The effect of acamprosate on alcohol and food craving in patients with alcohol dependence

Introduction

The balance between inhibitory (gamma aminobutyric acid; GABAergic) and excitatory (glutamatergic) neurotransmission is thought to be associated with craving for alcohol and food. The anticraving effect of acamprosate is thought to be mediated through modifying the balance of GABA and glutamate. Recent studies in animals have suggested that acamprosate may have non-selective effects on craving for both alcohol and food.

Methods

The influence of acamprosate for reducing craving for alcohol and food was assessed in 204 in-patients with alcohol dependence (96 patients treated with acamprosate, PWA; 108 patients were not treated PNA) was assessed at baseline and following 1, 2, and 4 weeks of treatment.

Results

There was a significant reduction in craving for alcohol over 4 weeks of treatment in both PWA and PNA groups, but without significant group differences. In contrast, a reduction in food craving was observed only in the PWA group. In addition, there was a significant increase of body mass index (BMI) in the PNA group but not the PWA group over the 4-week period.

Discussion

These results demonstrate acamprosate nonselective effects on craving for drinking and eating in alcoholic patients.     

Attention-deficit/hyperactivity disorder (ADHD) symptoms, craving to smoke, and tobacco withdrawal symptoms in adult smokers with ADHD

Background

Tobacco withdrawal symptoms may be confounded with attention-deficit/hyperactivity disorder (ADHD) symptoms among smokers with ADHD.

Objective

(1) To assess overlap between ADHD symptoms and tobacco/nicotine withdrawal symptoms and craving; (2) to assess the relationship between craving or withdrawal symptoms and the effect of osmotic-release oral system methylphenidate (OROS-MPH) on ADHD symptoms; (3) to assess the association of ADHD symptoms, craving, and withdrawal symptoms with abstinence.

Methods

Secondary analysis of a randomized, placebo controlled smoking cessation trial assessing the efficacy of OROS-MPH taken in addition to nicotine patch among individuals with ADHD. ADHD symptoms, withdrawal symptoms, and craving were assessed at baseline and 2, 4 and 6 weeks after a target quit day.

Results

Withdrawal symptoms and craving showed limited and modest overlap with ADHD symptoms prior to abstinence but more extensive and stronger correlation after quit day. Compared to placebo, OROS-MPH reduced ADHD symptoms; this effect was attenuated by controlling for withdrawal symptoms, but not by craving. Craving, but not ADHD symptoms and withdrawal symptoms, was associated with abstinence during the trial.

Conclusion

When treating smokers with ADHD (1) craving, rather than tobacco withdrawal symptoms or ADHD symptoms may be the more effective therapeutic smoking cessation targets; (2) careful distinction of craving, withdrawal symptoms, and ADHD symptoms when assessing withdrawal phenomena is needed.     

Smoking history, nicotine dependence, and changes in craving and mood during short-term smoking abstinence in alcohol dependent vs. control smokers

Objective

The goal of this study was to compare lifetime cigarette smoking, severity of nicotine dependence, and subjective effects of short-term tobacco abstinence in abstinent alcohol dependent (AD) and control smokers.

Method

AD (n = 119) and control (n = 55) ever-smokers were compared on tobacco use history and nicotine dependence. Negative affect and craving to smoke were examined in a subsample of currently smoking AD (N = 34) and control (N = 19) participants during a 6-h period of tobacco abstinence using the Profile of Mood States (POMS) and the Questionnaire on Smoking Urges-Brief (QSU-B).

Results

Although AD smokers did not differ from controls on heaviness of smoking, they were more likely to meet lifetime criteria for nicotine dependence. AD smokers also reported more withdrawal symptoms and were more likely to endorse withdrawal-related depressed mood during past smoking reduction or abstinence periods. During short-term abstinence, AD smokers were more likely to report high craving to smoke for negative affect relief within the first 150 min of tobacco abstinence, but did not differ from controls on overall craving to smoke or withdrawal-related negative affect on the POMS.

Conclusions

Results support previous findings that AD smokers have a greater prevalence of nicotine dependence and more severe nicotine withdrawal, with a greater propensity toward withdrawal-related depressed mood. These results, along with our novel finding that greater craving to smoke in abstaining smokers with AD is specific to negative affect-related craving, suggest that negative reinforcement may be a particularly salient factor in the maintenance of tobacco use among individuals with AD.     

The impact of pre-cessation varenicline on behavioral economic indices of smoking reinforcement

Background

Varenicline was developed to aid smoking cessation by reducing smoking reinforcement. The present study tests this reinforcement–reduction hypothesis among smokers preparing to quit.

Method

After a one-week baseline, treatment-seeking smokers were randomized to receive three weeks of varenicline or placebo (Weeks 2–4). During each of the four weeks of the study, smokers completed a hypothetical cigarette purchase task (CPT) via handheld devices in their natural environment. Behavioral economic measures of simulated smoking if cigarettes were free (demand intensity), sensitivity of consumption to increasing price (elasticity), and price at which purchases would drop to 0 (breakpoint) were estimated.

Results

The exponential demand equation fit the purchase task data well across subjects and time. As predicted, demand intensity decreased and sensitivity to price (elasticity) increased over time. However, changes in demand intensity did not differ by treatment group. Contrary to our hypothesis that varenicline would increase sensitivity to price, the placebo group tended to become more elastic in their purchases during Weeks 2 and 3; the groups did not differ in elasticity at Week 4. Breakpoint did not vary by group, time, or their interaction.

Conclusion

Simulated smoking demand can be validly assessed in the natural environment of treatment-seeking smokers. Simulated demand indices of smoking reinforcement diminished as smokers approached their target quit date. However, there was no evidence that varenicline facilitated these changes over a three‐week period, leaving open the mechanisms by which varenicline reduces smoking rate prior to cessation and improves long-term abstinence.     

Alcohol use and negative consequences among active duty military personnel

Aims

An examination of alcohol use patterns in the active duty military to determine the relations of drinking levels and self-reported negative outcomes.

Design

A population-based cross-sectional study design using two-stage complex sampling methodology.

Setting

Paper and pencil surveys were administered anonymously in groups at 64 U.S. military installations worldwide.

Participants

Randomly selected active duty members (28,546) at major military installations representing the total active force, with the exception of recruits, cadets, and incarcerated personnel.

Measures

Personnel were classified into five drinking levels ranging from abstainer to heavy drinker based on quantity and frequency of alcohol intake. Negative outcomes were measured as self-reported serious consequences of alcohol use and alcohol-related productivity loss. Risk for other alcohol related problems was assessed by the Alcohol Use Disorders Identification Test (AUDIT).

Findings

Alcohol negative outcomes showed a curvilinear dose–response relationship with drinking levels. Higher levels of drinking were associated with higher rates of alcohol problems, but problem rates were notably higher for heavy drinkers. Heavy alcohol users showed nearly three times the rate of self-reported serious consequences and over twice the rate of self-reported productivity loss than moderate/heavy drinkers. Heavy drinkers also had the highest risk for alcohol problems on the AUDIT. One fifth of military personnel were heavy drinkers and were most likely aged 18 to 35.

Conclusions

Prevention and clinical interventions should include a major focus on heavy drinkers. Commanders and peers should be trained in recognizing signs of heavy alcohol use and in approaching heavy alcohol users in a way that will foster positive attitudes as opposed to defensiveness and stigma.     

Varenicline,low dose naltrexone,and their combination for heavy-drinking smokers: human laboratory findings

Rationale

Heavy-drinking smokers constitute a sizeable and hard-to-treat subgroup of smokers, for whom tailored smoking cessation therapies are not yet available.

Objectives

The present study used a double-blind, randomized, 2?×?2 medication design, testing varenicline alone (VAR; 1 mg twice daily), low dose naltrexone alone (L-NTX; 25 mg once daily), varenicline plus naltrexone, and placebo for effects on cigarette craving and subjective response to alcohol and cigarettes in a sample (n?=?130) of heavy-drinking daily smokers (≥10 cigarettes/day).

Methods

All participants were tested after a 9-day titration period designed to reach a steady state on the target medication. Testing was completed at 12 h of nicotine abstinence, after consuming a standard dose of alcohol (target breath alcohol concentration?=?0.06 g/dl) and after smoking the first cigarette of the day.

Results

The combination of VAR?+?L-NTX was superior to placebo, and at times superior to monotherapy, in attenuating cigarette craving, cigarette and alcohol “high,” and in reducing ad-lib consumption of both cigarettes and alcohol during the 9-day medication titration period.

Conclusions

These preliminary findings indicate that clinical studies of the combination of VAR?+?L-NTX for heavy drinkers trying to quit smoking are warranted and may ultimately improve clinical care for this sizeable and treatment-resistant subgroup of smokers.     

Topiramate treatment for alcoholic outpatients recently receiving residential treatment programs: A 12-week,randomized, placebo-controlled trial

Background

Initiation of a relapse prevention medication is crucial at the end of alcohol detoxification. This study aimed to examine the efficacy and safety of topiramate for alcoholism in patients receiving a residential treatment program of alcohol detoxification and post-acute treatment.

Methods

This was a 12-week, randomized, double-blind, placebo-controlled trial of topiramate for alcoholism in patients receiving a residential treatment program. Individuals with DSM-IV alcohol dependence with minimal withdrawal were enrolled. Participants were randomly assigned to receive either 100–300 mg/day of topiramate or placebo. Primary outcomes were given as percentages of heavy drinking days and time to first day of heavy drinking. Other drinking outcomes, craving, and health-related quality of life were evaluated.

Results

A total of 106 participants were randomized to receive topiramate (n = 53) or placebo (n = 53). Twenty-eight participants of the topiramate group (52.8%) and 25 participants of the placebo group (47.2%) completed the study. Averaged over the trial period, there was no significant difference between groups on the mean percentages of heavy drinking days [1.96 (−1.62 to 5.54), p = .28]. Log rank survival analysis found no difference of time to first day of heavy drinking between topiramate and placebo groups (61.8 vs. 57.5 days, respectively; χ² = 0.61, d.f. = 1, p = .81). Other secondary outcomes were not significantly different between groups.

Conclusions

By using a conservative model for data analysis, we could not detect the effectiveness of topiramate in this particular population. As the sensitivity analysis showed a trend of its benefit, further studies in larger sample sizes are still warranted.     

Affect and craving: Positive and negative affect are differentially associated with approach and avoidance inclinations

Background

Research on reactivity to alcohol and drug cues has either ignored affective state altogether or has focused rather narrowly on the role of negative affect in craving. Moreover, until recently, the relevant analyses of affect and craving have rarely addressed the ambivalence often associated with craving itself. The current study investigated how both negative and positive affect moderate approach and avoidance inclinations associated with cue-elicited craving in a clinical sample diagnosed with substance use disorders.

Methods

One hundred forty-four patients (age range of 18–65, mean 42.0; n = 92 males) were recruited from an inpatient detoxification unit for substance abuse. Participants completed a baseline assessment of both positive and negative affect prior to completing a cue-reactivity paradigm for which they provided self-report ratings of inclinations to approach (use) and avoid (not use) alcohol, cigarettes, and non-psychoactive control substances (food and beverages).

Results

Participants with elevated negative affect reported significantly higher approach ratings for cigarette and alcohol cues, whereas those high in positive affect showed significantly higher levels of avoidance inclinations for both alcohol and cigarette cues and also significantly lower approach ratings for alcohol cues, all relative to control cues.

Conclusions

Results for negative affect are consistent with previous cue reactivity research, whereas results for positive affect are unique and call attention to its clinical potential for attenuating approach inclinations to substance use cues. Further, positive affect was related to both approach and avoidance inclinations, underscoring the utility of a multidimensional conceptualization of craving in the analysis.     

A double-blind, placebo-controlled pilot trial of acamprosate for the treatment of cocaine dependence

Background

Acamprosate is a medication shown to be effective for the treatment of alcohol dependence. Although the exact mechanism of action of acamprosate is unknown, evidence suggests that it decreases excitatory amino acid activity by post-synaptic inhibition of the NMDA subtype of glutamate receptors. It is possible that the activity of acamprosate via modulating glutamatergic activity could also reduce craving for cocaine and impact abstinence in cocaine dependence. Therefore, we conducted a double-blind placebo-controlled pilot trial of acamprosate for the treatment of cocaine dependence.

Methods

Sixty male and female cocaine dependent patients were included in a nine week double-blind, placebo-controlled trial. After a one-week baseline, patients were randomized to receive acamprosate 666 mg three times daily or identical placebo tablets for eight weeks. The primary outcome measure was cocaine use as determined by twice weekly urine drug screens.

Results

Thirty-six patients (60%) completed the trial, with no significant between-group difference in treatment retention. Percent cocaine positive urine drug screens did not differ between the two groups. Acamprosate was no better than placebo in reducing cocaine craving, reducing cocaine withdrawal symptoms, or improving measures of drug use severity from the Addiction Severity Index. Adverse events in this trial were generally mild and were evenly distributed between the two groups.

Discussion

Acamprosate was well tolerated but was no more efficacious than placebo in promoting abstinence from cocaine in cocaine dependent patients. Acamprosate does not appear to be a promising medication for the treatment of cocaine dependence.     

Validation of the Dutch version of the brief young adult alcohol consequences questionnaire (B-YAACQ)

Purpose

The purpose of this study was to validate the Dutch version of the Brief Young Adult Alcohol Consequences Questionnaire (B-YAACQ).

Method

The B-YAACQ was translated into the Dutch language and 800 students were invited to complete the questionnaire. A number of drinking behaviors were also assessed; including weekly drinking, age of drinking onset, and blood alcohol concentration on a typical night out. Students also completed a short version of the Alcohol Use Disorders Identification Test (AUDIT-PC).

Results

Data from 667 undergraduate and graduate students (184 men and 483 women) who reported alcohol use during the past year was used in the analysis. On average, students in this study report 4.7 alcohol-related consequences. The Dutch B-YAACQ was shown to have a high reliability and validity: Cronbach's Alpha was 0.816, and B-YAACQ scores correlated significantly with AUDIT-PC scores (r = 0.747). B-YAACQ scores correlated significantly (p < 0.01) with various drinking variables, including drinking onset age, drinking days per week, alcoholic drinks per week, number of drinks on a night out and blood alcohol concentration when returning home.

Conclusion

The Dutch B-YAACQ is a useful new tool for screening of alcohol-related consequences.     

Ten-year stability and variability, drinking patterns, and impairment in community youth with diagnostic orphan status of alcohol dependence

Objective

Some adolescents and young adults who do not fulfill criteria for DSM-IV alcohol abuse (AA) report symptoms of DSM-IV alcohol dependence (AD) below the diagnostic threshold (diagnostic orphans, DOs; 1 or 2 symptoms). Contemporarily, little is known on the long-term stability, risk of progression to AD, impairment, and drinking patterns possibly associated with this status in the first decades of life.

Aim

(1) To identify prevalence rates of the DO status from adolescence to early adulthood. To investigate (2) stability and variability of the DO status over time and (3) associations between DO status, drinking patterns and impairment in comparison to subjects with AA, with AD, or without any symptoms.

Method

N = 2039 community subjects (aged 14–24 years at baseline) were assessed at baseline and at about four and ten years after baseline. DSM-IV AUD diagnoses were obtained with the DIA-X/M-CIDI.

Results

About 11–12% of the sample was classified as DOs at all waves. Over a period of ten years, 18% of DOs were stable in their diagnosis and additional 10% progressed to AD. DOs were comparable to subjects with AA in drinking patterns, impairment and stability of diagnostic status. DOs progressed to AD significantly more often than AA. AD was associated with highest levels in all outcomes of interest.

Conclusions

The DO status in adolescence and early adulthood is associated with considerable stability, risk of progression and problematic alcohol intake. In consequence, it can be meaningful for the timely identification of early stages of clinically relevant alcohol problems. For subjects with DO status early specific interventions are required.