Psychometric properties of the German Penn Alcohol Craving Scale.

Craving for alcohol is an important diagnostic criterion in alcohol use disorder (AUD) and an established predictor of future relapse. The 5-item Penn Alcohol Craving Scale (PACS) is one of the most widely used questionnaires to quantify craving and has been translated into different languages. It is assumed that the PACS constitutes one factor, although theoretical considerations suggest an additional second factor. We conducted stability and factor analyses (principal component and confirmatory factor analyses) of the German PACS (PACS-G) in samples of patients with AUD from the following three German study sites: Erlangen, N = 188 (mean age: 47.1 years, 43.5% female); Mannheim, N = 440 (45.5 years, 28.6% female); Hannover, N = 107 (48.1 years, 48.6% female). In our samples, the 2-factor solution of the PACS-G version is more stable than the internationally assumed 1-factor solution. The resulting two PACS-G subscores 'difficulty to resist' (items 4 and 5) and 'thoughts about alcohol' (items 1, 2, and 3) have an internal consistency (Cronbach's alpha) of 0.80 ≤ α ≤ 0.90, m = 0.86 and 0.86 ≤ α ≤ 0.91, m = 0.89 with an overlap of R2 = 62%. We found good convergent validity assessed via the Craving Automatized Scale-Alcohol and the Obsessive-Compulsive Drinking Scale, but also correlations with depression and anxiety assessed via the Beck's Depression and Anxiety Inventories. This study is the first to provide evidence for a 2-factor solution ('difficulty to resist' and 'thoughts about alcohol') underlying the PACS-G version.

The Role of Unawareness, Volition, and Neural Hyperconnectivity in Alcohol Use Disorder: A Functional Magnetic Resonance Imaging Study.

BACKGROUND: Automated alcohol craving and habitual alcohol consumption characterize the later stages of alcohol use disorder (AUD). This study reanalyzed previously collected functional neuroimaging data in combination with the Craving Automated Scale for Alcohol (CAS-A) questionnaire to investigate the neural correlates and brain networks underlying automated drinking characterized by unawareness and nonvolition. METHODS: We assessed 49 abstinent male patients with AUD and 36 male healthy control participants during a functional magnetic resonance imaging-based alcohol cue-reactivity task. We performed whole-brain analyses examining the associations between CAS-A scores and other clinical instruments and neural activation patterns in the alcohol versus neutral contrast. Furthermore, we performed psychophysiological interaction analyses to assess the functional connectivity between predefined seed regions and other brain areas. RESULTS: In patients with AUD, higher CAS-A scores correlated with greater activation in dorsal striatal, pallidal, and prefrontal regions, including frontal white matter, and with lower activation in visual and motor processing regions. Between-group psychophysiological interaction analyses showed extensive connectivity between the seed regions inferior frontal gyrus and angular gyrus and several frontal, parietal, and temporal brain regions in AUD versus healthy control participants. CONCLUSIONS: The present study applied a new lens to previously acquired alcohol cue-reactivity functional magnetic resonance imaging data by correlating neural activation patterns with clinical CAS-A scores to elucidate potential neural correlates of automated alcohol craving and habitual alcohol consumption. Our results support previous findings showing that alcohol addiction is associated with hyperactivation in habit-processing regions, with hypoactivation in areas mediating motor and attention processing, and with general hyperconnectivity.

Examining a brief measure and observed cutoff scores to identify reward and relief drinking profiles: Psychometric properties and pharmacotherapy response.

BACKGROUND: Precision medicine approaches attempt to reduce variability in alcohol use disorder (AUD) outcomes by identifying patient characteristics that predict response to a particular treatment. Recent work has examined the extent to which individuals with AUD may seek alcohol to enhance positive experiences (reward drinking) or relieve negative states (relief drinking) and shown that a high reward/low relief phenotype predicts naltrexone treatment response. Yet, limitations of reward/relief drinking measures may hamper efforts to translate findings to clinical practice. We sought to refine a brief measure of reward/relief drinking and develop cutoff scores to identify reward/relief subgroups that predict pharmacotherapy response. METHODS: The Inventory of Drinking Situations (IDS), used in previous studies to measure reward/relief drinking, was administered to 426 participants (77% male; average age = 45.3) in a clinical trial examining naltrexone and acamprosate. RESULTS: Item response theory and tests of differential item functioning across sex, age, and alcohol dependence severity were used to create a 10-item measure, titled the Reward and Relief IDS (RR-IDS). Cutoff scores on the RR-IDS for the reward/relief drinking subgroups were identified using latent profile and area under the curve analyses. The cutoff scores demonstrated good construct validity. Individuals in the high reward/low relief subgroup who received naltrexone or acamprosate had a decreased likelihood of heavy drinking (large effect sizes) versus those who received placebo. CONCLUSIONS: The RR-IDS is a practical measure for identifying reward/relief subgroups and predicting pharmacotherapy response. Pending replication of these findings, the RR-IDS could be a critical precision medicine tool for prescribing AUD medications.

Validation of the German Version of the Mind Excessively Wandering Scale (MEWS-G).

Increasing evidence shows that unintentional mind wandering is linked to Attention Deficit Hyperactivity Disorder (ADHD) and that its frequency contributes to symptom severity and functional impairment in ADHD. However, empirical data on mind wandering in adult ADHD are still scarce, and a validated scale to assess mind wandering in German adult ADHD patients is lacking. The primary aim of this study is to assess the psychometric properties of the German version of the recently published Mind Excessively Wandering Scale (MEWS-G) in terms of factorial structure and factor stability, internal consistency and construct validity. Analyses were performed in 128 adults with ADHD, clinical and healthy controls. As described for the original English 15-item version of the scale, we found lowest item-total-correlations for items 6, 10 and 14 with item-total correlation of all: 0.54/ADHD: 0.32 (item 6), all: 0.55/ADHD: 0.39 (item 10) and all: 0.11/ADHD: -0.04 (item 14). Item-total correlations for the remaining items were 0.65-0.86 and Cronbach Alpha was 0.96 indicating good internal consistency of the 12-item version of scale, on which we based all further analyses. Principal component analysis indicated a one- and two- factorial scale structure respectively explaining 71.7 % and 78.7 % of variance. Both factors showed good stability with lower stability of the factor-2 solution if sample size was reduced. The two-factorial solution also had many cross-loadings and a strong correlation of both factors in confirmatory factorial analysis (rf1f2 = 0.87). It probably describes related and interdependent, but not distinct facets of mind wandering, which strongly argues for the one factorial structure of the scale. Mean MEWS-G score in ADHD was 23.77 ± 7.85 compared to 7.64 ± 7.27 in controls (p < .0001). According to ROC, the optimal cut-off point to discriminate ADHD and controls is at MEWS-G score = 13. On the symptom level, MEWS-G score was correlated with ADHD, depressive and total psychiatric symptom scores, on the personality level with neuroticsm and negatively with conscientiousness and on the functional level with social interaction difficulties and impaired self-efficacy. In summary, our study shows that MEWS-G is a reliable, valid instrument to assess spontaneous mind wandering in adult ADHD and to discriminate between ADHD and controls.

Precision Medicine in Alcohol Dependence: A Controlled Trial Testing Pharmacotherapy Response Among Reward and Relief Drinking Phenotypes.

Randomized trials of medications for alcohol dependence (AD) often report no differences between active medications. Few studies in AD have tested hypotheses regarding which medication will work best for which patients (ie, precision medicine). The PREDICT study tested acamprosate and naltrexone vs placebo in 426 randomly assigned AD patients in a 3-month treatment. PREDICT proposed individuals whose drinking was driven by positive reinforcement (ie, reward drinkers) would have a better treatment response to naltrexone, whereas individuals whose drinking was driven by negative reinforcement (ie, relief drinkers) would have a better treatment response to acamprosate. The goal of the current analysis was to test this precision medicine hypothesis of the PREDICT study via analyses of subgroups. Results indicated that four phenotypes could be derived using the Inventory of Drinking Situations, a 30-item self-report questionnaire. These were high reward/high relief, high reward/low relief, low reward/high relief, and low reward/low relief phenotypes. Construct validation analyses provided strong support for the validity of these phenotypes. The subgroup of individuals who were predominantly reward drinkers and received naltrexone vs placebo had an 83% reduction in the likelihood of any heavy drinking (large effect size). Cutoff analyses were done for clinical applicability: individuals are reward drinkers and respond to naltrexone if their reward score was higher than their relief score AND their reward score was between 12 and 31. Using naltrexone with individuals who are predominantly reward drinkers produces significantly higher effect sizes than prescribing the medication to a more heterogeneous sample.

Development and validation of the craving automated scale for alcohol.

BACKGROUND: Alcohol consumption has been suggested to be associated with a dysregulation in habit formation and execution in dependent patients. Although there are established craving questionnaires assessing various components of craving, to our knowledge, no questionnaire exists to assess habitual and automated substance intake. In this study, we present and validate the "Craving Automated Scale for Alcohol" (CAS-A), a newly developed questionnaire assessing craving and other components of automated addictive behavior. METHODS: Forty-three recently detoxified alcohol-dependent patients were examined in an inpatient setting using a cross-sectional design. The CAS-A, a self-report questionnaire, was applied. According to classical test theory, we conducted principal component analyses (PCAs) to identify the components of CAS-A, after which we validated it using established craving questionnaires. Thirty-two healthy participants served as a control group. RESULTS: Our first-order PCA identified a 5-factor solution. A second-order analysis then identified 2 general factors. These factors were partially associated with established craving measures and with the severity of dependence. CONCLUSIONS: Our findings suggest that CAS-A assesses additional components of addictive behavior compared to established measures. We interpret the 5 CAS-A factors as "only aware in hindsight," "no deliberate decision," "contrary to intention," "no perception," and "no control." We suggest the 2 general factors be interpreted as "unaware" and "nonvolitional." Our results indicate that the CAS-A indeed assesses some components of automated craving and automated drinking behavior in a more sophisticated way than established questionnaires. The CAS-A as a retrospective questionnaire can be considered to be a trait rather than a state measure.

Factors affecting cognitive function of opiate-dependent patients.

BACKGROUND: A wide range of studies found that opiate-dependent patients suffer from cognitive impairment due to a number of different factors. However, this issue has never been examined systematically. Thus, the aim of the present study is to provide a comprehensive analysis of factors that might contribute to cognitive impairment of opiate-dependent patients and specifically differentiates between various cognitive abilities as these might be impacted differently. METHODS: Based on a comprehensive review of the literature with regard to previous findings and suggestions about which factors might affect cognitive functioning, we assessed a wide variety of variables related to substance use and opiate-dependence as well as demographic and socioeconomic variables. Cognitive functioning was assessed through a neuropsychological test-battery. RESULTS: We found that the duration of opiate dependence and maintenance treatment, as well as additional substance consumption (alcohol, amphetamines, and cocaine) are the main variables contributing to cognitive impairment in the domains of attention and executive function. Comorbid depressive symptoms negatively affected reaction times. There was no evidence for the role of demographic variables like age and education on cognitive functioning. CONCLUSIONS: Our findings suggest that it might be important in the treatment of opiate dependence to address the consumption of additional substances and to closely monitor the negative effects of maintenance treatment on cognitive functioning.

The vicious circle of perceived stigmatization, depressiveness, anxiety, and low quality of life in substituted heroin addicts.

BACKGROUND: Perceived stigmatization of drug addicts may interact with negative mood states and thus may contribute to the maintenance of addictive behavior. METHODS: Opiate maintenance patients (n = 106) and an unselected comparison group (n = 144) rated self-report questionnaires about perceived stigmatization, quality of life (QoL), depressiveness, anxiety, self-esteem, addiction characteristics, and social support. RESULTS: 63% of opiate maintenance patients felt discriminated in contrast to 16% of the comparison group. Perceived stigmatization was rated higher by opiate maintenance patients, and all domains of QoL were rated lower, even when statistically controlling depressiveness, anxiety and social factors. Perceived stigmatization was correlated to depressiveness, anxiety, low self-esteem and low QoL, but not addiction characteristics and social support. Structural equation models revealed anxiety and the pathway depressiveness enhancing feelings of being stigmatized resulting in low self-esteem to explain 74% of variance in mental QoL, whereas anxiety and a pathway stigmatization inducing depressiveness leading to low self-esteem explained 49% of variance in physical QoL. CONCLUSIONS: A vicious circle of stigmatization, negative affective states and low QoL was confirmed. In addition to societal antistigma campaigns, antidepressive and anxiolytic therapy might have the potential to diminish feelings of being stigmatized and to improve QoL.

Effects of repeated withdrawal from alcohol on recovery of cognitive impairment under abstinence and rate of relapse.

AIMS: Several authors suggest that withdrawal from alcohol could cause neurotoxic lesions in the frontal lobe and thereby affect cognitive function. In line with this, previous studies have demonstrated greater cognitive impairment of alcohol-dependent patients with two or more previous detoxifications (Hi-detox) compared with patients with less than two detoxifications (Lo-detox). The aim of the present study was to investigate whether repeated withdrawal from alcohol affects recovery of cognitive function and is related to relapse. METHODS: Forty-eight alcohol-dependent patients (Hi-detox: n = 31, Lo-detox: n = 17) and 36 healthy controls underwent a comprehensive neuropsychological test-battery. Patients were tested after completion of detoxification (T1) and 3 (T2, n = 35) and 6 (T3, n = 28) months after discharge. Healthy controls were tested at T1 (n = 36) and T2 (n = 16). Drinking behaviour was assessed at all times. RESULTS: Patients performed significantly worse than controls at T1 as well as T2 with regard to attention/executive function. Recovery of attention/executive function was observed within the second 3 months after discharge, but the Hi-detox group performed worse than the Lo-detox group. No association with relapse was observed. CONCLUSION: This study provides first evidence, that repeated withdrawal from alcohol might be associated with reduced brain plasticity as indicated by a delay of recovery from impairment of attention/executive function. However, little evidence was found for a direct influence of cognitive impairment on treatment success.

Orexin and leptin are associated with nicotine craving: a link between smoking, appetite and reward.

OBJECTIVE: Preclinical data suggest modulating effects of both orexin/hypocretin and leptin on dopaminergic transmission in mesolimbic reward pathways. This indicates a possible role of both peptides in reward function and motivation, and thus in addictive diseases. The aim of this study was to examine the possible association between orexin and leptin, and nicotine craving in smokers in a clinical case-control study under standardized conditions. METHODS: We compared orexin and leptin, ACTH and cortisol plasma concentrations (RIA) between tobacco smokers (n=60) during early nicotine withdrawal and healthy controls (n=64). Motivational aspects of nicotine craving were additionally assessed in the smoking participants using the Questionnaire of Smoking Urges (QSU). RESULTS: As main results we detected a significant negative correlation between orexin plasma concentration and nicotine craving (r=-0.28; p<.05), and a positive association between craving and leptin plasma concentration (r=0.29; p<.05). CONCLUSIONS: Our results show an association between craving for nicotine and plasma concentrations of orexin and leptin suggesting that both peptides interfere with the dopaminergic transmission during nicotine withdrawal in a bidirectional manner and, thus, modulate craving for nicotine.

Consultation-liaison psychiatry in general hospitals: improvement in physicians' detection rates of alcohol use disorders.

BACKGROUND: In the general hospital setting, alcohol-use disorders very commonly remain undetected. OBJECTIVE: The authors hypothesized that including a consultation-liaison (C-L) psychiatrist in primary-care rounds would improve detection rates of alcohol-use-disorders. METHOD: Patients (N=165) on two medical wards were screened by means of the Alcohol Use Disorders Identification Test. Diagnoses were confirmed with the International Diagnostic Checklists and compared with physicians' detection rates. C-L intervention included demonstrations of standardized diagnostic procedures in order to change primary-care physicians' behavior. RESULTS: Primary-care-physicians' detection rates of alcohol-use disorders increased significantly after implementation of the C-L service, whereas no significant differences were observed on the control ward. CONCLUSION: Tentative data thus underscore the efficacy of C-L psychiatry for detection and intervention in alcohol-use disorders.

Impairment of cognitive abilities and decision making after chronic use of alcohol: the impact of multiple detoxifications.

AIMS: In the present study, the effect of previous detoxifications on prefrontal function and decision making was examined in alcohol-dependent patients. Further, we examined whether the length of abstinence affects cognitive function. METHODS: Forty-eight alcohol-dependent patients were recruited from an inpatient detoxification treatment facility and cognitive function was compared to a control group of 36 healthy controls. The patient population was then divided into a group of patients with less than two previous detoxifications (LO-detox group, n = 27) and a group of patients with two or more previous detoxifications (HI-detox group, n = 21) and cognitive function was compared. In addition, cognitive function of recently (i.e. less than 16 days; median split) and longer abstinent patients was compared. We assessed prefrontal function, memory function and intelligence. RESULTS: Alcoholics, when compared to healthy controls, performed worse with regard to the performance index Attention/Executive function. Cognitive impairment in these tasks was pronounced in recently abstinent patients. We found no significant differences between HI-detox and LO-detox patients with regard to the Attention/Executive function. However, in the IOWA gambling Task, the HI-detox group seemed to be less able to learn to choose cards from the more advantageous decks over time. CONCLUSIONS: Our results provide additional evidence for cognitive impairment of alcohol-dependent patients with regard to tasks sensitive to frontal lobe function and underline the importance of abstinence for these impairments to recover. We found only little evidence for the impairing effects of repeated withdrawal on prefrontal function and we suggest that executive function is affected earlier in dependence.

[Development and validation of an overall instrument to measure craving across multiple substances: the Mannheimer Craving Scale (MaCS)]. / Entwicklung und Validierung eines Instrumentes zur substanzunabhängigen Erfassung von Craving: Die Mannheimer Craving Scale (MaCS).

OBJECTIVE: Based on the Obsessive Compulsive Drinking Scale (OCDS) we developed and validated the Mannheimer Craving Scale (MaCS) for quantitative measurements of craving across different substances and suitable for multiple substance abuse. METHODS: The MaCS questionnaire measures obsessive-compulsive symptoms in the context of substance abuse and dependence similar to the OCDS. The MaCS consists of 12 items and 4 additional items. Validation of the instrument was performed by means of 3 assessments of each subject within a project for the evaluation of a detox treatment on n = 292 alcohol and drug-dependent patients with multiple substance abuse. RESULTS: The MaCS showed a very high measurement reliability (0.87 < alpha < 0.93). The MaCS total score correlated highly significant with the mean intensity of craving (0.47 < r (tc ) < 0.64, p < 0.0001), with the maximum of craving (0.52 < r (tc) < 0.69, p < 0.0001), and with the frequency of craving (0.43 < r (tc) < 0.65, p < 0.0001) measured by means of analogue scales. CONCLUSIONS: The MaCS for overall measurements of craving across multiple substances showed very good reliability and validity. In combination with a simple and universal feasibility of the MaCS these results indicate the applicability in everyday clinical settings as well as scientific settings.

Modifications of the Obsessive Compulsive Drinking Scale (OCDS-G) for use in longitudinal studies.

Since the application of the Obsessive Compulsive Drinking Scale (OCDS) has been reported to be problematic when used to measure alcohol craving in longitudinal studies, we examined the following questions: (1) Is it possible to skip problematic quantity items? (2) Is the score calculation rule using the higher value of item pairs necessary? (3) Can the shortened version of the OCDS be applied alternatively? We examined two samples including a total of 355 alcohol-dependent patients: a multi center study sample (n=149) and a validation control sample (n=206). Neither an advantage of the score calculation rule nor the necessity of including items regarding alcohol consumption could be demonstrated. The exclusion of consumption items lead to a clear, stable 2-factor structure with a maximum stability (.81-.91). Retest-reliability ranged from r(tt)=.73 to r(tt)=.76 at an average time interval of 5 weeks. Concerning stability (.68-.81) and reliability (r(tt)=.76), the short version turned out to be equivalent. The short version of the OCDS seems to be sufficient. If different effects on cognitive and behavioral levels are expected, the 12-item version without the quantity items should be applied.

The startle reflex in alcohol-dependent patients: changes after cognitive-behavioral therapy and predictive validity for drinking behavior. A pilot study.

BACKGROUND: Previous studies demonstrated an attenuation of the affect-modulated startle reflex when alcohol-dependent patients were viewing alcohol-associated pictures. This indicates an appetitive valence of these stimuli. We used the affect-modulated startle reflex to assess the effects of behavioral treatment on the emotional processing of alcohol-associated stimuli. Further, we examined whether the affect-modulated startle reflex is a predictor of treatment success. METHODS: Forty-three alcohol-dependent patients (21 females, mean age 45.67 years, SD 9.45) were recruited consecutively from an inpatient alcohol detoxification facility where patients attended a 3-week detoxification program including cognitive-behavioral treatment to successfully handle high-risk situations. The eye blink component of the affect-modulated startle response, self-reported cue-induced craving and skin conductance responses to alcohol-associated and control slides were assessed before and after treatment. Changes were analyzed using repeated measures analysis of variance. Drinking behavior was assessed in the 6 months following treatment, and a regression analysis was performed to evaluate the predictive validity of the affect-modulated startle response for drinking behavior. RESULTS: Drinking behavior as well as craving and skin conductance responses decreased significantly over time. The pattern of the affective modulation of the startle reflex was not altered over time. However, startle modulation and relapse were related, and within the group of relapsers, startle modulation was a significant predictor of drinking behavior. CONCLUSIONS: Our results suggest that the modulation of the startle reflex may reflect more enduring and permanent processes of emotional responding to alcohol-related cues than autonomic arousal and self-reported craving, and that startle modulation by alcohol-associated cues may be a better predictor of drinking behavior for relapsers than other measures. Further studies including a control condition are necessary to validate these findings.

Alcoholism in women: is it different in onset and outcome compared to men?

Onset and course of alcohol dependence show gender related differences (telescoping effect) suggesting that women are more vulnerable to chronic alcohol consumption. This raises the question whether the differences are associated with a different treatment outcome as well. We hypothesized, that alcohol dependent women with a telescoping course show a less favourable treatment outcome compared to men. We investigated 212 alcohol dependent patients; matching 106 consecutively admitted women with 106 men drawn from a total sample of 343 male patients. The treatment program consisted of a 6 week inpatient treatment and 12 months of outpatient aftercare. We assessed milestone variables in development and course of alcoholism and carried out standardized diagnostic tests, physical and blood examinations to evaluate the course of the disease and treatment outcome. Overall, we confirm the telescoping effect, a faster progression in the course of alcoholism (developmental events and adverse consequences) in women compared to men ("telescoping effect"). However, despite the telescoping effect treatment outcome was similar in women and men. During the inpatient treatment program no alcohol relapse occurred. Throughout the 12 months outpatient treatment we found no significant differences in the survival analysis between women (283.29+/-11.26 days) and men (284.72+/-12.16 days). At the end of the 12 months both groups had an abstinence rate of approximately 50% and a drop-out rate of 33%.

Enhanced expression of interleukin-18 in serum and pancreas of patients with chronic pancreatitis.

AIM: To investigate interleukin-18 (IL-18) in patients with chronic panreatitis (CP). METHODS: We studied 29 patients with CP and 30 healthy controls. Peripheral blood mononuclear cells (PBMC) were isolated and incubated with 50 mmol/L ethanol, lipopolysaccharide (LPS) (doses 25 g/L, 250 g/L, 2500 g/L) and both agents for 24 h. Levels of IL-18 in the supernatants, and levels of IL-18, IL-12, interferon (IFN)-gamma and soluble CD14 in the serum were analysed by ELISA technique. Expression of IL-18 in PBMC was investigated by reverse-transcription (RT)-PCR. IL-18 protein levels in CP tissue and in normal pancreas were studied by ELISA technique. IL-18 levels in PBMC and pancreatic tissue were determined by Western blot. Immunohistochemistry for pancreatic IL-18 expression was performed. RESULTS: In patients, IL-18 serum levels were significantly enhanced by 76% (mean: 289.9+/-167.7 ng/L) compared with controls (mean: 165.2+/-43.6 ng/L; P<0.0005). IL-12 levels were enhanced by 25% in patients (18.3+/-7.3 ng/L) compared with controls (14.7+/-6.8 ng/L, P=0.0576) although not reaching the statistical significance. IFN-gamma and soluble CD14 levels were not increased. In vitro, LPS stimulated significantly and dose-dependently IL-18 secretion from PBMC. Incubation with ethanol reduced LPS-stimulated IL-18 secretion by about 50%. The mRNA expression of IL-18 in PBMC and the response of PBMC to ethanol and LPS was similar in CP patients and controls. In PBMC, no significant differences in IL-18 protein levels were detected between patients and controls. IL-18 protein levels were increased in CP tissues compared to normal pancreatic tissues. IL-18 was expressed by pancreatic acinar cells and by infiltrating inflammatory cells within the pancreas. CONCLUSION: IL-18 originates from the chronically inflammed pancreas and appears to be involved in the fibrotic destruction of the organ.

Effects of treatment with acamprosate on beta-endorphin plasma concentration in humans with high alcohol preference.

Treatment with acamprosate, a compound used for relapse prevention treatment of alcoholism, was recently shown to be associated with increased plasma concentration of beta-endorphin in rats selectively bred for high alcohol preference. The aim of our study was to prove this result in a comparative clinical study with a corresponding design. We studied 51 alcohol dependent patients following alcohol withdrawal during treatment with acamprosate versus placebo for 4 weeks. Data were analyzed for patients with high alcohol preference (HP) and low alcohol preference (LP) by dichotomizing the sample according to median alcohol intake prior to detoxification. In line with pre-clinical data, beta-endorphin plasma concentration in HP patients was significantly lower compared with LP patients. Four weeks of treatment with acamprosate resulted in a significantly increased beta-endorphin plasma concentration compared with placebo and a significant difference in HP patients but not in LP patients. In conclusion, acamprosate seems to modulate the endogenous opioid system. Our data are in accordance with the assumption that the effect of acamprosate on endorphin plasma concentrations is mainly based on the effect in the high preferring subgroup. Since beta-endorphin deficiency was earlier associated with alcohol craving and anxiety during withdrawal, abstinence maintaining effects of acamprosate might at least be partially related with the ability to modulate opioidergic activity especially in the subsample of HP patients with an attenuated opioidergic activity during this state.

A pilot study of oxcarbazepine versus acamprosate in alcohol-dependent patients.

OBJECTIVES: This pilot study has been designed to collect preliminary data on the use of a new antiepileptic drug in the management of alcoholic patients. Oxcarbazepine (OXC) blocks voltage-sensitive sodium channels. Its metabolite reduces high-voltage-activated calcium currents in striatal and cortical neurons, thus reducing glutamatergic transmission at corticostriatal synapses. This reduction is of interest in the treatment of alcohol dependence, as acamprosate (ACP) modulates NMDA receptors, resulting in an inhibition of glutamatergic transmission. Furthermore, OXC has revealed a mood-stabilizing effect in bipolar affective disorders. We have compared OXC with ACP in relapse prevention in recently withdrawn alcohol-dependent patients. METHODS: We investigated the efficacy and safety of OXC (vs ACP) by conducting a 24-week randomized, parallel-group, open-label, clinical trial on 30 acutely detoxified alcoholic patients. Survival analyses (Kaplan-Meier) were performed to look for evidence of a longer "survival" of patients receiving OXC. We assessed time to first severe relapse and additional secondary endpoints. RESULTS: After withdrawal, time to severe relapse and time to first consumption of any ethanol by OXC patients were not longer than for ACP patients. Abstinent patients in both study groups showed a significantly lower obsessive compulsive drinking scale-German version (OCDS-G) than relapsed patients. No undesired effects occurred when OXC patients consumed alcohol. CONCLUSION: Our findings indicate that it could be worthwhile to test relapse prevention using OXC in an adequate sample. While the current sample size clearly limits further conclusions from this pilot study, it is noteworthy that OXC is well tolerated, even when alcohol is on board. Thus, in medication-based relapse prevention, OXC could be a promising alternative for alcoholic patients unable to benefit from ACP or naltrexone or those who have affective liability. OXC certainly merits a larger placebo-controlled trial.