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.

Heart rate stress response dampening: the impact of alcohol, family history, and gender on at risk children and siblings.

OBJECTIVE: In the following study we tested the stress response dampening (SRD) model which postulates that stress responses are more likely to be attenuated by alcohol in individuals at risk for alcohol dependence than in persons without that risk. In a laboratory experiment we examined a) if SRD effects exist for both sons and healthy daughters of alcohol dependent fathers, and b) if SRD effects exist for siblings of alcohol dependent males. METHODS: We recruited 104 subjects at risk and 51 matched control subjects. In a laboratory experiment, study subjects received alcohol in one of two laboratory sessions and a stress paradigm served to elicit heart rate stress responses. RESULTS: Heart rate stress responses were attenuated by alcohol in female family history positive (FHP) and female family history negative (FHN) subjects, however not in males. A multiple regression analysis revealed "Heart Rate Stress Response in the Non-Alcohol Condition" and "Blood Alcohol Level" as significant predictors of SRD. CONCLUSIONS: According to our findings, females carry a distinct risk for developing alcohol dependence, regardless of their family history and regardless of their degree of familial relationship. This is an important issue for devising models concerning the development and maintenance of alcohol dependence in females. The study extends the current research literature, which mainly focuses on male subjects at risk, by including female subjects at risk, as well as siblings at risk of both genders.

Why is disulfiram superior to acamprosate in the routine clinical setting? A retrospective long-term study in 353 alcohol-dependent patients.

AIMS: To compare the long-term effectiveness of acamprosate (ACP) and disulfiram (DSF) in the treatment of alcohol dependence and their effectiveness in regard to patient characteristics, within a naturalistic outpatient treatment setting. METHOD: Retrospective data from 2002 to 2007 were analysed on 353 alcohol-dependent subjects in outpatient treatment, who, according to the patient's and the clinician's mutual decision, received either supervised DSF (with thrice-weekly appointments) or ACP (once-weekly appointments) following an inpatient alcohol detoxification treatment. Abstinence was assessed by alcohol breathalyzer, patients' self-report, urine and serum analyses, and overall physicians' rating. RESULTS: Baseline data in terms of current addictive behaviour and course of disease differed between groups to the disadvantage of the DSF group; compared to the ACP group, subjects treated with DSF showed a longer duration of alcohol dependence, higher amounts of daily alcohol consumption and more alcohol detoxification treatments in their history. In follow-up, Kaplan-Meier survival analysis revealed significant differences between groups in the primary and secondary measures of outcome (P always <0.01). Time elapsed before the first alcohol relapse as well as attendance to outpatient treatment and cumulative alcohol abstinence achieved within outpatient treatment was explicitly longer in the DSF group. A longer duration of alcohol dependence predicted a favourable treatment outcome in the DSF group, while for the ACP group the chances for a successful treatment increased with shorter duration of alcohol dependence. CONCLUSIONS: This study supports the thesis that supervised DSF is an important component of alcoholism treatment, and it appears to be more effective than the treatment with ACP particularly in patients with a long duration of alcohol dependence.

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.

[A case of compulsive buying--impulse control disorder or dependence disorder?]. / Ein Fall von Kaufsucht--Impulskontrollstörung oder Abhängigkeitserkrankung?

OBJECTIVE: It is unclear what disease entity causes compulsive buying. In ICD-10 and DSM-IV, compulsive buying is classified as "Impulse control disorder--not otherwise classified". Some publications interpret compulsive buying rather as a dependence disorder. METHOD: We present the case of a male patient with compulsive buying syndrome. We discuss the close relationship to dependence disorders. CONCLUSIONS: The patient showed symptoms which would normally be associated with a dependence disorder. On the basis of a wider understanding of the dependency concept, as it is currently being discussed, we believe that the patient has shown a typical buying behavior that has presumably activated a reward loop similar to that of a substance dependency.

Oxcarbazepine in rapid benzodiazepine detoxification.

OBJECTIVE: This study aims at evaluating the tolerability and efficacy of the antiepileptic drug oxcarbazepine in benzodiazepine detoxification in ten patients. METHODS: In this case study of an inpatient withdrawal program, each of the ten patients was detoxified using oxcarbazepine and completed withdrawal successfully without the occurrence of withdrawal symptoms. The detoxification program followed an outlined dosage scheme with oxcarbazepine increase and benzodiazepine tapering. RESULTS: The rapidity of benzodiazepine detoxification using oxcarbazepine was remarkable, benzodiazepine withdrawal being completed in as little as 11 days. CONCLUSIONS: The results support the assumption that oxcarbazepine is a valuable drug for inpatient benzodiazepine withdrawal programs.

Neuropsychological functioning of opiate-dependent patients: a nonrandomized comparison of patients preferring either buprenorphine or methadone maintenance treatment.

OBJECTIVES: In the present study, we investigated whether buprenorphine as a partial mu-opioid receptor agonist is associated with less cognitive impairment than methadone. METHODS: Neuropsychological functioning of opioid-dependent patients, previously assigned to methadone (MMP, n = 30) or buprenorphine (BMP, n = 26) maintenance treatment according to their own preference, was compared and dose effects were investigated. RESULTS: MMP and BMP performed equally well on all measures of neuropsychological functioning including the trail making test, the continuous performance test, and a vigilance task. However, patients receiving a higher dose of methadone were impaired in a vigilance task. CONCLUSIONS: In a free-choice administration of methadone or buprenorphine, there seems to be no difference in cognitive functioning. Possible explanations are discussed.

Exploring the link between gender, sensation seeking, and family history of alcoholism in cortisol stress-response dampening.

Many studies have demonstrated an inverse association between cortisol and risk-taking behaviors, with high-sensation seekers (HSS) showing lower cortisol levels. We investigated the potential link between sensation seeking (SS) and stress-induced stress responses, as well as alcohol-induced stress-response-dampening (SRD) effects in cortisol. First, we hypothesized that HSS would show inverse SRD effects in cortisol. Second, we hypothesized that females would display similar SRD effects to males. Third, we hypothesized an independent relationship between SS and family history (FH) with regard to alcohol-induced SRD effects in cortisol. 86 healthy men and women participated in two laboratory sessions, receiving alcohol in one of the two. Experimental stress paradigms were administered and serum cortisol was measured. SRD effects in cortisol developed for both genders in low-sensation seekers (LSS), but not in HSS. This study contributes to current literature by (1) supporting the association between SS and cortisol, (2) demonstrating that SRD effects in cortisol of females is inversely related to SS, and (3) demonstrating an independent relationship between SS and FH with regard to alcohol-induced SRD effects in cortisol.

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.

[Rapid inpatient tramadol-detoxification using oxcarbazepine]. / Rasche stationäre Tramadolentgiftung mit Oxcarbazepin.

UNLABELLED: CONCERN: With reference to the case history, we report on an in-patient detoxification of a tramadol addicted subject by application of the antiepileptic substance oxcarbazepine. METHOD: The patient's medical records as well as the progress of the in-patient tramadol detoxification by means of oxcarbazepine are outlined. Additionally, we discuss our experience with oxcarbazepine as a therapeutic alternative in addiction medicine. CONCLUSION: Also in tramadol withdrawal the good tolerability as well as mood stabilising effects during and after inpatient treatment was shown. The inpatient time for withdrawal was significantly shortened, in contrast to the past no withdrawal symptoms emerged and after inpatient treatment the patient showed up abstinent and was affective good stabilised.

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%.

Cue exposure in the treatment of alcohol dependence: effects on drinking outcome, craving and self-efficacy.

OBJECTIVES: The aim of the present study was to investigate beneficial effects of cue exposure treatment for alcohol dependence by contrasting it with a well-established treatment approach. We hypothesized that cue exposure treatment is associated with a stronger decline of craving, a stronger increase in self-efficacy and has beneficial effects on drinking behaviour after discharge. DESIGN AND METHODS: Sixty-three patients with a diagnosis of alcohol dependence were recruited from an in-patient alcohol-detoxification facility. Patients were sequentially assigned to either cue exposure or a standard cognitive-behavioural treatment. We assessed self-reports of craving and self-efficacy prior to treatment participation and at the end of treatment. Drinking behaviour was assessed in the 6-month period following discharge. RESULTS: Both treatments were associated with a reduction of self-reported craving and an increase in self-reported measures of self-efficacy. A significant time x treatment interaction indicated a greater increase in self-reported measures of self-efficacy after cue exposure treatment. Measures of drinking behaviour showed clearly that both treatments were efficacious. Relapse rates and drinking-related variables were not significantly different for the two treatments at the 6-month follow-up. There was preliminary evidence that suggests that cue exposure therapy may be more effective for patients with severe alcohol dependence. CONCLUSIONS: With respect to drinking behaviour, cue exposure and standard cognitive-behavioural treatment seem to be equally effective for patients with a moderate severity of alcohol dependence. Further studies are necessary to specify criteria for differential treatment indication.

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.

Alcohol-induced heart rate response dampening during aversive and rewarding stress paradigms in subjects at risk for alcoholism.

Individuals with a family history of alcoholism (FH+) are at risk to develop alcohol problems. In several studies, psychophysiological stress responses were more attenuated by alcohol in FH+ than in FH- subjects. However, it is not clear from these studies, if this stronger stress-response dampening effect of alcohol (SRD) in FH+ subjects is confined to aversive stimuli, or would hold for nonaversive stress conditions as well. Also, male and female FH+ subjects seem to respond differently to the alcohol challenge, but have rarely been directly compared in a SRD paradigm. Participants were 54 female and 63 male healthy adults; 31 women were daughters (DOAs) and 40 men were sons (SOAs) of alcohol-dependent fathers. The remaining 23 women (DONAs) and 23 men (SONAs) had no FH of any alcohol use disorder. The participants took part in two laboratory sessions, one with and one without alcohol. In each session, three stressor procedures were presented. Heart rate is the main dependent variable in this report. SOAs, but not SONAs showed a tendency towards SRD. Among female participants, a strong SRD occurred, but contrary to our expectation only in controls. Stress responses and SRD effects were somewhat stronger in the aversive than in the rewarding task. The extent of alcohol induced SRD was strongly influenced by BAL and the amplitude of the stress response in the no-alcohol condition (multiple regression analysis). Thus, aversive tasks might have the advantage of eliciting stronger stress responses than rewarding tasks, thereby providing better conditions for observing differences in alcohol induced SRD between FH+ and FH- subjects.

Low efficacy of non-opioid drugs in opioid withdrawal symptoms.

Opioid withdrawal, stress or cues associated with opioid consumption can induce opioid craving. If opioids are not available, opioid-dependent patients usually search for alternative drugs. Because several non-opioid drugs stimulate the endogenous opioidergic system, this concept may explain their frequent use by opioid-dependent patients. We hypothesized that non-opioid drugs alleviate opioid withdrawal symptoms and are therefore consumed by opioid addicts. We asked 89 opioid-dependent patients participating in an out-patient opioid maintenance program to estimate the potential of several non-opioid drugs in being able to alleviate opioid withdrawal. We applied a five-point Lickert scale (1 = very good reduction of opioid withdrawal; 5 = no reduction of opioid withdrawal). Patients could also indicate a worsening of opioid withdrawal. Values (mean +/- SD) were: for benzodiazepines, 3.2 +/- 1.1; tricyclic antidepressants, 3.6 +/- 1.1; cannabis, 3.6 +/- 1.0; alcohol, 4.1 +/- 1.1; cocaine, 4.2 +/- 1.1; amphetamine, 4.4 +/- 0.9; nicotine, 4.7 +/- 0.7; and caffeine, 4.9 +/- 0.5. A worsening of opioid withdrawal was reported by 62% of the patients for cocaine, 62% for amphetamine, 50% for caffeine, 37.5% for cannabis, 27% for nicotine, 26% for alcohol, 8% for tricyclic antidepressants and 3% for benzodiazepines. Our study shows a low efficacy of non-opioid drugs in alleviating opioid withdrawal symptoms. The data basis of this study was good and the sample was suitable to be asked for estimations of drug-drug interactions. Of the patients, 26 - 62% even reported a worsening of opioid withdrawal for cannabis, alcohol, cocaine and amphetamine. Only benzodiazepines and tricyclic antidepressants were reported to have a moderate positive effect on opioid withdrawal.

The long-term course of alcoholism, 5, 10 and 16 years after treatment.

AIMS: To discover the long-term stability of drinking behaviour following an in-patient treatment episode. DESIGN: Three follow-up periods were used at 5, 10 and 16 years. The patients were classified as being abstinent, improved or unimproved on the basis of self-reported drinking behaviour. Patients who could not be interviewed at follow-up were classified as unimproved. SETTING: An alcohol dependence treatment programme at the University Hospital Tuebingen, Germany. PARTICIPANTS: We were able to locate all 96 patients at the 16-year follow-up. Seventy were alive and 26 had died. We collected information from 59 of the 70 surviving patients. The remaining 11 patients could be located and were definitely alive. FINDINGS: Thirty-eight of the 70 patients were abstinent, 10 were improved and 22 (including the 11 living patients without further information) were classified as unimproved. Our main finding indicates that the so-called 'improved drinking' is very inconsistent over time. In contrast, the abstinent and unimproved patients were much more stable in their drinking behaviour. CONCLUSIONS: This study extends our knowledge of the drinking trajectory and outcome from only a few years of follow-up to 16 years. Complete abstinence and unimproved drinking behaviour were the most stable drinking patterns observed over the long term, confirming study results obtained primarily from English-speaking countries.

Correlation of stable elevations in striatal mu-opioid receptor availability in detoxified alcoholic patients with alcohol craving: a positron emission tomography study using carbon 11-labeled carfentanil.

BACKGROUND: The pleasant effects of food and alcohol intake are partially mediated by mu-opiate receptors in the ventral striatum, a central area of the brain reward system. Blockade of mu-opiate receptors with naltrexone reduces the relapse risk among some but not all alcoholic individuals. OBJECTIVE: To test the hypothesis that alcohol craving is pronounced among alcoholic individuals with a high availability of mu-opiate receptors in the brain reward system. DESIGN: Patients and comparison sample. The availability of central mu-opiate receptors was measured in vivo with positron emission tomography (PET) and the radioligand carbon 11-labeled carfentanil in the ventral striatum and compared with the severity of alcohol craving as assessed by the Obsessive Compulsive Drinking Scale (OCDS). SETTING: Hospitalized care. PARTICIPANTS: Volunteer sample of 25 male alcohol-dependent inpatients assessed after detoxification of whom 12 underwent PET again 5 weeks later. Control group of 10 healthy men. MAIN OUTCOME MEASURES: After 1 to 3 weeks of abstinence, the availability of mu-opiate receptors in the ventral striatum, including the nucleus accumbens, was significantly elevated in alcoholic patients compared with healthy controls and remained elevated when 12 alcoholic patients had these levels measured 5 weeks later (P<.05 corrected for multiple testing). Higher availability of mu-opiate receptors in this brain area correlated significantly with the intensity of alcohol craving as assessed by the OCDS. CONCLUSIONS: Abstinent alcoholic patients displayed an increase in mu-opiate receptors in the ventral striatum, including the nucleus accumbens, which correlated with the severity of alcohol craving. These findings point to a neuronal correlate of alcohol urges.

Stress response dampening indexed by cortisol in subjects at risk for alcoholism.

OBJECTIVE: This study examines the stress-response-dampening (SRD) hypothesis of alcoholism from a novel vantage point. Various investigators have demonstrated that persons considered to be at risk for developing alcohol-related problems exhibit attenuation of stress reactions in psychologically challenging experimental sessions after receiving alcohol. These studies have used autonomic nervous system measures for indexing stress responses. In our report we address the question of whether people with a family history of alcoholism exhibit dampening effects of ethanol in the response of a classical stress hormone (i.e., cortisol). METHOD: Subjects in this report were 46 healthy male and 40 healthy female adult subjects; 36 of the men were sons and 28 of the women were daughters of alcohol-dependent fathers (sons of alcoholics, SOAs; daughters of alcoholics, DOAs); 12 women and 10 men had no family history of any alcohol use disorders (daughters of nonalcoholics, DONAs; sons of nonalcoholics, SONAs). The subjects were part of a large-scale project in which participants received two laboratory sessions with exposure in each to three experimental paradigms involving psychological stress while various psychophysiological and neuroendocrine measures were taken. In one of the sessions alcohol was administered. RESULTS: In the 1-hour period after termination of the stress paradigms, SOAs showed significantly lower plasma cortisol levels on laboratory days with alcohol administration than on days without alcohol administration at two of the three poststress sampling points. DOAs, however, did not exhibit a dampening pattern for cortisol. In the two control groups of SONAs and DONAs, no stress response attenuation effects of alcohol were observed. CONCLUSIONS: The results of experimental laboratory work with individuals at risk of alcoholism in the present and other studies add to the validity of SRD models of this disorder. Research strategies that should provide direct evidence for the SRD hypothesis are addressed in the Discussion section.