Craving in Alcohol-Dependent Patients After Detoxification Is Related to Glutamatergic Dysfunction in the Nucleus Accumbens and the Anterior Cingulate Cortex

The upregulation of glutamatergic excitatory neurotransmission is thought to be partly responsible for the acute withdrawal symptoms and craving experienced by alcohol-dependent patients. Most physiological evidence supporting this hypothesis is based on data from animal studies. In addition, clinical data show that GABAergic and anti-glutamatergic drugs ameliorate withdrawal symptoms, offering indirect evidence indicative of glutamatergic hyperexcitability in alcohol-dependent subjects. We used proton magnetic resonance spectroscopy to quantify the glutamate (Glu) levels in healthy control subjects and in alcohol-dependent patients immediately after detoxification. The volumes of interest were located in the nucleus accumbens (NAcc) and the anterior cingulate cortex (ACC), which are two brain areas that have important functions in reward circuitry. In addition to Glu, we quantified the levels of combined Glu and glutamine (Gln), N-acetylaspartate, choline-containing compounds, and creatine. The Glu levels in the NAcc were significantly higher in patients than in controls. Craving, which was measured using the Obsessive Compulsive Drinking Scale, correlated positively with levels of combined Glu and Gln in the NAcc and in the ACC. The levels of all other metabolites were not significantly different between patients and controls. The increased Glu levels in the NAcc in alcohol-dependent patients shortly after detoxification confirm the animal data and suggest that striatal glutamatergic dysfunction is related to ethanol withdrawal. The positive correlation between craving and glutamatergic metabolism in both key reward circuitry areas support the hypothesis that the glutamatergic system has an important role in the later course of alcohol dependence with respect to abstinence and relapse.     

Personality Disorders Among Alcohol-Dependent Patients Manifesting or not Manifesting Cocaine Abuse: A Comparative Pilot Study

This study assessed personality disorders (PDs) in 158 alcohol-dependent outpatients (62 manifesting cocaine abuse and 96 without cocaine abuse) with the International Personality Disorders Examination interview between 2003 and 2006. Thirty-nine alcohol-dependent/cocaine abusers (62.9% of this group) and 51 only alcohol-dependent patients (53.1% of this group) manifested at least one PD. There were no statistically significant differences between groups in the overall prevalence rate of PDs. The most prevalent PDs, among the alcohol-dependent/cocaine abusers, were antisocial (21%), narcissistic (14.5%), and borderline (11.3%) PDs. The most frequently diagnosed PDs among the only alcohol-dependent patients were obsessive–compulsive (20.8%), paranoid (10.4%), and dependent (9.4%) PDs. There were significant differences between the groups. The study limitations are discussed.     

Physical Pain and History of Suicidal Behaviors in Alcohol-Dependent Patients Entering Treatment in Poland

Background: Individuals with alcohol use disorders have been shown to be at increased risk for suicidal behaviors and chronic pain. Objectives: The aim of this study was to conduct initial analyses of the association between current physical pain and the likelihood of suicidal behavior history in alcohol-dependent patients entering treatment in Poland. Methods: A sample of 366 (73.5% men and 26.5% women) participants were recruited from alcohol treatment centers in Warsaw, Poland. Information was obtained about a history of lifetime suicidal behavior, past 4-week pain level, demographics, social functioning, childhood abuse, depressive symptoms, severity of alcohol and sleep problems. Results: A total of 118 individuals (32.2%) reported at least one suicidal behavior during their lifetime. In unadjusted analyses, there was a significant association between a history of lifetime suicidal behavior and a moderate or greater experience of physical pain during the last four weeks. Other variables that were significantly associated with suicidal behaviors were: younger age, history of childhood abuse, depressive symptoms, sleep problems, consequences of drinking, and lower social support. In the multivariate logistic regression analysis, only experience of moderate or greater pain, age, and depressive symptoms remained significantly associated with a history of suicidal behavior. Conclusions: The experience of physical pain is significantly associated with a lifetime history of suicidal behavior in alcohol-dependent patients. Clinicians should be aware of these associations when conducting assessments and treating alcohol use disorders.     

Feasibility of a Supportive Other Intervention for Opiate-Dependent Patients Entering Inpatient Detoxification

Involvement of supportive others (SOs; defined as patient’s most important person) in substance use treatment is widely accepted as a valuable addition, but is not routinely implemented during inpatient detoxification for opioid use disorders. The current study explores the feasibility of a brief SO intervention for individuals detoxing from opioids. Data regarding ability to identify an SO, the nature of the SO relationship, and willingness to invite an SO to help with long-term abstinence were collected from 369 patients attending inpatient opioid detoxification. For those unwilling to participate in an SO intervention, possible barriers to participation were examined. Results indicated that the majority (71.8%) of patients were willing to involve SOs, and that they believed that their SO was supportive of their treatment (88.1%). Those unwilling to invite an SO reported that their identified SO was a young child or that they wanted to make life changes independently. We conclude that SO involvement in substance use treatment at the time of opioid detoxification is feasible and could be engaged in future interventions.     

Markers for Patients with Alcohol Problems in an Outpatient General Medicine Clinic

Our purpose was to determine the correlation among alcohol problems, certain health habits, and hypertension in a general internal medicine outpatient setting. Two-hundred eighty-seven patients who were undergoing complete examinations in a general internal medicine department of a large multispecialty clinic were asked to participate in a lifestyle survey interview, which included questions regarding social history, gastrointestinal complaints, anxiety/depression, sexual dysfunction, and the Alcohol Use Disorders Identification Test (AUDIT). Charts were screened for documentation of alcohol problems and the presence of hypertension. Correlations between alcohol problems (defined as an AUDIT score 8) and the presence of hypertension were made using chi-square tests for categorical variables and the t test for continuous variables. Of the 287 patients contacted, 12 refused, 3 were ineligible, and 29 had incomplete data precluding analysis, yielding a total of 233 patients (81%) who were included in the analysis. Sixty percent were female, 76% were white, and the mean age was 53 years. The overall prevalence of alcohol problems was 7.3% and less than one-quarter of those patients had chart documentation of an alcohol problem. Thirty percent of those patients had a diagnosis of hypertension. No statistically significant correlation between a positive AUDIT and hypertension was found. Failure to use seat belts (P = 0.020), history of smoking (P < 0.001), alcohol use within 24 hr of the office visit (P < 0.001), and self-reported family history of alcoholism (P = 0.012) were significantly more likely in patients with active alcohol problems. There was no difference in somatic complaints between patients with and patients without alcohol problems. We identified certain health behaviors which served as markers for patients with active alcohol problems in an outpatient setting. Physician diagnosis of alcohol problems (sensitivity of 24% in this study) may be improved with attention to such markers. Despite the known relationship of excess alcohol use and elevations in blood pressure, we found no statistically significant correlation between these variables in our study. Symptomatic concerns of the patient appear to be too nonspecific to distinguish patients with and without alcohol problems.     

Aversion to Injection Limits Acceptability of Extended-Release Naltrexone Among Homeless,Alcohol-Dependent Patients

ABSTRACT

Background: Ending homelessness is a major priority of the Department of Veteran Affairs (VA), and alcohol use can be a barrier to stable housing. Clinical trials suggest that depot extended-release naltrexone (XR-NTX) is efficacious in reducing alcohol consumption among alcohol-dependent subjects. Methods: An open-label, randomized pilot study sought to examine the feasibility and effectiveness of XR-NTX versus oral naltrexone to improve alcohol consumption and housing stability among homeless, alcohol-dependent veterans at the Providence Veteran Affairs Medical Center. Results: Of 215 potential candidates approached over a 16-month recruitment period, only 15 agreed to consider study entry and 7 were randomized. The primary reasons given for refusal were not wanting an injection; fear of needles; and not wanting to change drinking habits. Only 1 participant in the XR-NTX group returned after the first injection. Three participants in the oral naltrexone group attended all 7 visits and had good outcomes. Conclusions: Although XR-NTX has demonstrated efficacy in reducing heavy drinking, limited acceptance of the injection might reduce its effectiveness among homeless, alcohol-dependent patients.     

The therapeutic potential of gamma-hydroxybutyric acid for alcohol dependence: balancing the risks and benefits. A focus on clinical data

There is an increasing interest in studying the role of GABAergic medications in the treatment of alcohol dependence. The GABAergic drug gamma-hydroxybutyric acid (GHB) has been investigated in Europe as a possible treatment for alcohol dependence. In some European Countries, GHB has been approved as a treatment for alcohol dependence. However, this drug has also shown addictive properties, therefore raising questions about its safety in treating alcohol-dependent subjects. More recent research is focusing on the possibility of identifying alcohol-dependent subtypes without risk of developing GHB abuse. Finally, GHB and naltrexone combined together represent a possible approach deserving future investigations.     

Effects of a Single Lyric Analysis Intervention on Withdrawal and Craving With Inpatients on a Detoxification Unit: A Cluster-Randomized Effectiveness Study

Background: For patients hospitalized on inpatient detoxification units, reducing negative symptoms such as withdrawal and craving is a key treatment area. Although lyric analysis is a commonly utilized music therapy intervention for clients in substance abuse rehabilitation, there is a lack of randomized controlled music therapy studies systematically investigating how lyric analysis interventions can affect patients on a detoxification unit. Objective: The purpose of this cluster-randomized effectiveness study was to measure the effects of single-session group lyric analysis interventions on withdrawal and craving with patients on a detoxification unit. A secondary purpose of this study was to determine if relationships existed between treatment effects and participants’ familiarity with the song. Methods: Participants (N = 144) were cluster-randomized to experimental (posttest only) or wait-list control (pretest only) conditions to provide treatment to all participants in an inclusive single-session design. Results: Although participants in the experimental condition had lower withdrawal and craving means than participants in the control condition, these differences were not significant. Familiarity of the song in the lyric analysis was not related to withdrawal or craving. Conclusion: Group-based lyric analysis interventions may be effective for temporarily relieving withdrawal and craving in patients on a detoxification unit. Familiarity of the song did not affect results. Implications for clinical practice, suggestions for future research, and limitations are provided.     

Validation study of the Turkish version of the Yale - Brown obsessive compulsive scale for heavy drinking in a group of male patients

Psychometric properties of Turkish version of the Yale Brown Obsessive Compulsive Scale for heavy drinking (YBOCS-hd) were examined in alcohol-dependent male patients. Factor structure, internal consistency and discriminant validity of the YBOCS-hd were analysed in a sample of 117 male patients diagnosed with alcohol dependence. To study its convergent validity, the YBOCS-hd was correlated with the Addiction Severity Index in 34 of the patients. A test - retest reliability study was performed on the data from 34 patients. Correlation between the YBOCS-hd total score and the ASI Alcohol Use score was moderate (r = 0.51). One factor explained 50.2% of the variance. The YBOCS-hd was able to discriminate the groups abstinent for less than 1 month and a second group with at least 1 month of abstinence. Test - retest correlation was high (r = 0.81, ICC = 0.81). The Turkish version of the YBOCS-hd proved to be a reliable and valid instrument measuring craving in alcohol-dependent male individuals. [Ilhan IO, Demirbas H, Dogan YB. Validation study of the Turkish version of the Yale - Brown Obsessive Compulsive Scale for heavy drinking in a group of male patients. Drug Alcohol Rev2006;25:357 - 360]     

Outcome and Six Month Follow Up of Patients After Ultra Rapid Opiate Detoxification (URODSM)

Abstract

Objectives -(1) Evaluate the safety and efficacy of Ultra Rapid Opiate Detoxification (UROD); and (2) evaluate six month outcome data of patients choosing this method.

Design -Two center parallel group clinical trial. No grant funding.

Setting -Two academic medical centers.

Participants -Ninety-three men and 27 women, aged 18 to 55 years, with opiate dependency self selected to undergo detoxification.

Interventions -UROD followed by naltrexone maintenance and an aftercare program. UROD and aftercare costs were the responsibility of the patients and/or their significant others.

Main Outcomes Measure -(1) Completion of UROD as determined by a non reactive response to a naloxone challenge test under anesthesia and non reactive response to naltrexone administration before discharge. (2) Patient outcome as determined at six month follow up of UROD patients' self reported relapse free status confirmed by urine drug screen, significant other reports, and/or therapist reports.

Results -One hundred percent successful detoxification with UROD with low morbidity and no mortality. Relapse data were available for 111/123 procedures performed (90%), with 61/111 patients (55%) with reported relapse free status at the six month follow up interval.

Conclusions -For individuals who are addicted to opioids, the Ultra Rapid Opiate Detoxification method appears to be a viable treatment option.     

A Longitudinal Study of Drinking and Depression as Predictors of Insomnia in Alcohol-Dependent Individuals

Insomnia and depressive symptoms are common symptoms among alcohol-dependent (AD) patients. AD individuals (N = 364) were assessed during 2004–2009 in the Midwestern United States at baseline and 6-month intervals with the Sleep Problems Questionnaire, Time-Line Follow-Back interview, and the depression subscale of the Brief Symptom Inventory. Hierarchical Linear Modeling was used to analyze the data in this longitudinal study. When modeled separately, both quantity of drinking (p < .01) and depression (p < .001) predicted insomnia severity, controlling for time, age, and gender. Drinking also predicted depressive symptoms (p < .001), and its effect on insomnia was mediated by depression severity (p < .001).     

Aripiprazole for relapse prevention and craving in alcohol use disorder: current evidence and future perspectives

Introduction: Among other approaches, the modulation of the dopaminergic pathway has been advocated in the therapeutic management of Alcohol Use Disorders (AUD). A potential avenue toward the modulation of the dopaminergic pathway across varying substance disorders seems to be provided by aripiprazole, a second-generation antipsychotic characterized by a peculiar pharmacodynamics signature.

Areas covered: In this review, the authors provided a qualitative synthesis and a critical perspective on the efficacy of aripiprazole in relapse prevention and craving in AUD. A systematic search was carried out through MEDLINE/Embase/PsycINFO/Cochrane Library from inception until September 2015, combining free terms and MESH headings for the topics of AUD and aripiprazole as following: (((Alcohol use Disorder) OR (Alcohol use)) AND aripiprazole).

Expert opinion: Based both on a qualitative synthesis and a critical interpretation of the evidence, the authors submit that aripiprazole would promote alcohol abstinence and reduce the alcohol seeking behaviour possibly via dopaminergic and serotoninergic modulations at the fronto-subcortical circuits underpinning alcohol reward and craving, impulsive behaviour as well as reduce alcohol-related anxiety/low mood and anhedonia. However, due to the lack of published studies, a conclusive statement about any direct effect of aripiprazole in the prevention of craving and/or alcohol consumption is not possible.     

Alcohol Protracted Withdrawal Syndrome: The Role of Anhedonia

Aims: The aim of the present study is to characterize the relevance of withdrawal symptoms during the first 12 months of abstinence and their relation to anhedonia and craving. Methods: 102 detoxified subjects meeting clinical criteria for Alcohol Dependence in Remission were recruited at various time since the detoxification and subdivided into four groups according to the length of abstinence (group 1: 15–30 days; group 2: 30–90 days; group 3: 90–180 days; group 4: 180–360). Withdrawal symptomatology was assessed through the Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar). The Visual Analogue Scale (VAS) for craving, the Snaith–Hamilton Pleasure Scale (SHAPS) and the Subscale for Anhedonia in the Scale for the Assessment of Negative Symptoms (SANSanh) where the other instruments employed. Results: Both anhedonia and withdrawal symptoms were identified in all the groups considered. SHAPS score and VAS for craving showed a significant difference between group 1 and groups 2, 3, and 4. As to CIWA-Ar items, apart from “orientation/clouding of sensorium” that was higher in groups 3 and 4 with respect to both groups 1 and 2, withdrawal symptoms were not significantly different between the periods considered. SHAPS and SANSanh were positively correlated to CIWA-Ar total score, “nausea and vomiting,” and “headache/fullness in head.” Discussion: The results of this study suggest the relevance of protracted withdrawal well beyond the limited period following the abrupt cessation of alcohol intake. The clinical dimension of anhedonia cannot be separated from the other behavioral symptoms of withdrawal and should be considered as part of the same process.     

The Role of Clock in Ethanol-Related Behaviors

Mice with a mutation in the Clock gene (ClockΔ19) exhibit increased preference for stimulant rewards and sucrose. They also have an increase in dopaminergic activity in the ventral tegmental area (VTA) and a general increase in glutamatergic tone that might underlie these behaviors. However, it is unclear if their phenotype would extend to a very different class of drug (ethanol), and if so, whether these systems might be involved in their response. Continuous access voluntary ethanol intake was evaluated in ClockΔ19 mutants and wild-type (WT) mice. We found that ClockΔ19 mice exhibited significantly increased ethanol intake in a two-bottle choice paradigm. Interestingly, this effect was more robust in female mice. Moreover, chronic ethanol experience resulted in a long-lasting decrease in VTA Clock expression. To determine the importance of VTA Clock expression in ethanol intake, we knocked down Clock expression in the VTA of WT mice via RNA interference. We found that reducing Clock expression in the VTA resulted in significantly increased ethanol intake similar to the ClockΔ19 mice. Interestingly, we also discovered that ClockΔ19 mice exhibit significantly augmented responses to the sedative effects of ethanol and ketamine, but not pentobarbital. However, their drinking behavior was not affected by acamprosate, an FDA-approved drug for the treatment of alcoholism, suggesting that their increased glutamatergic tone might underlie the increased sensitivity to the sedative/hypnotic properties of ethanol but not the rewarding properties of ethanol. Taken together, we have identified a significant role for Clock in the VTA as a negative regulator of ethanol intake and implicate the VTA dopamine system in this response.     

Stage of Change as a Predictor of Abstinence Among Alcohol-Dependent Subjects in Pharmacotherapy Trials

In order to evaluate the stages of change model as a predictor of abstinence among alcoholics, we examined abstinence rates at the end of treatment and at a 6-month posttreatment follow-up in 113 alcohol-dependent subjects participating in two 12-week, placebo-controlled pharmacotherapy trials. Hierarchical logistic regression was used to examine the predictive validity of stages of change variables. At the end of treatment and at follow-up, individuals with a higher predisposition toward action were more likely to be abstinent. Subjects who received an active medication (buspirone or fluoxetine) were more likely also to remain abstinent during the 6-month posttreatment follow-up. Scores on measures of precontemplation, contemplation, and maintenance failed to predict abstinence either at the end of treatment or at follow-up. Although none of the stages of change measures were associated with treatment completion, married or cohabiting individuals were more likely to complete treatment. Despite that scores on the precontemplation, contemplation, and maintenance subscales were not associated with abstinence, a measure of readiness for action contributed significantly to the prediction model.     

Single Dose of 24 Milligrams of Buprenorphine for Heroin Detoxification: An Open-label Study of Five Inpatients

Abstract

Previous studies indicate that buprenorphine has efficacy in medically supervised opioid withdrawal, but the optimal dosing for maximum tolerability and ease of administration remains undetermined. Five heroin-dependent individuals entered this open-label study of inpatient detoxification with a single 24mg dose of buprenorphine. The mean Clinical Opiate Withdrawal Scale (COWS) score prior to buprenorphine administration was 17.6 (SD = 3.36). COWS scores declined significantly thereafter. There was one episode of precipitated withdrawal that resolved within four hours. Use of ancillary medications was minimal. This study suggests that a single high dose of buprenorphine can be used safely and effectively for inpatient detoxification.     

Cognitive Variables in Alcohol Dependent Patients with Elevated Depressive Symptoms: Changes and Predictive Utility as a Function of Treatment Modality

The aim of the current study was to examine, through posthoc analyses, changes in and predictive utility of mood-related cognitive variables as a function of treatment modality in a group of alcohol dependent patients with elevated depressive symptoms. In addition to the background partial hospital treatment for alcoholism which lasted a mean of 21.2 days, study patients (n = 35) received cognitive–behavioral treatment for depression (CBT-D) or a control treatment consisting of relaxation training (RTC). While both groups showed improvement on dysfunctional attitudes during treatment, only the CBT-D group improved on measures of alcohol-related expectancies. Changes in cognitive variables during treatment predicted drinking outcomes, and the predictors of drinking outcomes varied across the two treatments. Among the RTC patients, changes in positive alcohol-related expectancies were negatively correlated with drinking frequency and quantity at follow-up. However, for the CBT-D patients, changes in self-efficacy concerning negative mood situations and negative alcohol-related expectancies were negatively correlated with drinking at longer-term follow-up. The results of this study provide evidence concerning the mechanisms by which the treatment modalities examined may affect patient outcome. Although these results are preliminary in nature, they do suggest that future research might examine efforts to capitalize on these mechanisms through the facilitation of changes found to predict better drinking outcomes in this study.