Patient Perspectives on Pharmacotherapy of Alcohol Dependence.

INTRODUCTION: Pharmacotherapy with drugs like naltrexone or acamprosate is a well-evaluated element in the treatment of alcohol dependence (AD). However, in many countries, these medications are rarely administered. The objective of the present study was to identify from patients' perspective factors that prevent the initiation and compliance with pharmacological treatment of AD. METHODS: Patients from inpatient alcohol withdrawal treatment underwent a standardized interview. Questions included socio-demographic data, history of AD, treatment history, knowledge and personal experience regarding pharmacotherapy of AD, and personal views about the causes of AD. RESULTS: Three hundred patients (mean age 47.3 years, 27.7% female, mean duration of AD 8.9 years, 67% with a history of previous inpatient withdrawal treatment) were included. The majority of patients (58.7%) already knew drugs for the pharmacotherapy of AD. Thirty percent had ever used such medications, most often acamprosate. Except for disulfiram, pharmacotherapy of AD had lasted only a few weeks, on average. Medication usually had been applied without additional psychotherapy. No severe side effects were reported. Patients had often stopped pharmacotherapy on their own, when assuming they had reached stable abstinence. Openness to start pharmacotherapy for AD was currently stated by 67% of the total sample. In multiple logistic regression, openness was predicted by having a concept of AD as a medical disease and by a shorter duration of AD. DISCUSSION: To improve the administration of pharmacotherapy for AD implementation strategies should be systematically developed and evaluated with a focus on the concept of AD as a medical disease.

Shifted balance of dorsal versus ventral striatal communication with frontal reward and regulatory regions in cannabis-dependent males.

The transition from voluntary to addictive behavior is characterized by a loss of regulatory control in favor of reward driven behavior. Animal models indicate that this process is neurally underpinned by a shift in ventral-dorsal striatal control of behavior; however, this shift has not been directly examined in humans. The present resting state functional magnetic resonance imaging (fMRI) study employed a two-step approach to: (a) precisely map striatal alterations using a novel, data-driven network classification strategy combining intrinsic connectivity contrast with multivoxel pattern analysis and, (b) to determine whether a ventral to dorsal striatal shift in connectivity with reward and regulatory control regions can be observed in abstinent (28 days) male cannabis-dependent individuals (n = 24) relative to matched controls (n = 28). Network classification revealed that the groups can be reliably discriminated by global connectivity profiles of two striatal regions that mapped onto the ventral (nucleus accumbens) and dorsal striatum (caudate). Subsequent functional connectivity analysis demonstrated a relative shift between ventral and dorsal striatal communication with fronto-limbic regions that have been consistently involved in reward processing (rostral anterior cingulate cortex [ACC]) and executive/regulatory functions (dorsomedial prefrontal cortex [PFC]). Specifically, in the cannabis-dependent subjects, connectivity between the ventral striatum with the rostral ACC increased, whereas both striatal regions were uncoupled from the regulatory dorsomedial PFC. Together, these findings suggest a shift in the balance between dorsal and ventral striatal control in cannabis dependence. Similar changes have been observed in animal models and may promote the loss of control central to addictive behavior.

Interoceptive awareness, tension reduction expectancies and self-reported drinking behavior.

AIMS: Recent accounts have suggested the involvement of interoceptive processes in consumption behavior for alcohol and other drugs. However, there is a paucity of empirical support for a direct association with physiologically assessed individual differences in interoceptive awareness (IA). The current research explored this postulated link and examined the interplay with positive outcome expectancies of alcohol consumption. METHOD: IA of alcohol-dependent adult in- and outpatients was measured with an objective electrocardiogram heart rate tracking task. Tension reduction expectancies (TRE) and drinking compulsions/obsessions were assessed with self-report questionnaires. RESULTS: No direct associations of IA with drinking compulsions/obsessions were found. However, IA and TRE interacted as predictors of drinking compulsions and drinking obsessions. CONCLUSION: The results corroborate the suggestion that neglect of bodily feedback might be a maintaining factor for drinking behavior.

Development and implementation of quality indicators in a group of nine psychiatric hospitals.

Quality indicators (QI) are becoming increasingly important in mental healthcare in Germany. QI can be used for various purposes, such as for creating transparency as well as for benchmarking between hospitals. QI themselves are subject to high quality standards. The aim of this report is to describe the development and implementation of QI in a group of psychiatric hospitals. Since 2015, the LVR hospital group has developed and gradually implemented QI for the purposes of quality measurement, quality assurance and internal benchmarking in its nine psychiatric hospitals in a comprehensive, multidisciplinary, scientifically accompanied process. The full LVR-QI set, consisting of eight structure-, twelve process- and four outcome indicators as well as one patient satisfaction questionnaire, was implemented by 2019. In order to create high documentation quality and acceptance by clinicians, various implementation and dissemination strategies were used, such as written documentation manuals, staff training as well as regular face-to-face communication between the LVR hospitals, the LVR Institute for Health Services Research as the central coordinating body and the headquarters of the LVR hospital group. The QI led to a quality-oriented dialogue within and between the LVR hospitals.

Preliminary investigations on ethyl glucuronide and ethyl sulfate cutoffs for detecting alcohol consumption on the basis of an ingestion experiment and on data from withdrawal treatment.

Ethyl glucuronide (EtG) and ethyl sulfate (EtS) are commonly used alcohol markers for previous alcohol consumption. Nevertheless, the optimum EtG cutoff for urinary abstinence tests is still being discussed, and no cutoff has been recommended for EtS yet. The aim of this study was to verify cutoffs by investigating EtG and EtS concentrations (c(EtG) and c(EtS)) in the urine of healthy persons after drinking small, but realistic amounts of alcohol (one or two glasses of beer or white wine), and to look for the window of detection in strongly alcohol-intoxicated patients who were beginning withdrawal treatment. Very high EtG and EtS concentrations were measured in the first urine samples of patients under withdrawal treatment. However, 24 h later, concentrations decreased considerably, and c (EtG) < 0.5 mg/l and c (EtS) < 0.1 mg/l were determined in 26.7 % (4/13) and 13.3 % (2/13) of the samples, respectively. Concentrations above 0.1 mg/l (EtG) and 0.05 mg/l (EtS) were measured for 23.5 and 20.5 h after consuming 0.1 l of white wine or 0.33 l of beer, and 24 h after the experiment, 75 % (9/12) of the urine samples were tested negative for EtG and EtS using the following cutoffs: EtG 0.5 mg/l and EtS 0.1 mg/l. In half of the samples, concentrations below 0.1 mg/l (EtG) and 0.05 mg/l (EtS) were detected. Urinary cutoffs for EtG of 0.5 mg/l or higher are not suitable for testing abstinence. Even 0.1 mg/l is not effective to detect the intake of small amounts of alcohol in the context of abstinence tests. For EtS, 0.05 mg/l were found to be a potential cutoff to exclude the repeated intake of alcohol. Yet, further research is required to verify this cutoff. For a limited time period, EtG and EtS concentrations within the range of these cutoffs are also detectable after unintentional consumption of alcohol. Participants of abstinence programs have to be informed about the alcohol content of certain foods and beverages whose consumption is in conflict with strict abstinence.

Alterations of homocysteine serum levels during alcohol withdrawal are influenced by folate and riboflavin: results from the German Investigation on Neurobiology in Alcoholism (GINA).

AIMS: Various studies have shown that plasma homocysteine (HCY) serum levels are elevated in actively drinking alcohol-dependent patients a during alcohol withdrawal, while rapidly declining during abstinence. Hyperhomocysteinemia has been associated not only with blood alcohol concentration (BAC), but also with deficiency of different B-vitamins, particularly folate, pyridoxine and cobalamin. METHODS: Our study included 168 inpatients (110 men, 58 women) after admission for detoxification treatment. BAC, folate, cobalamin, pyridoxine, thiamine and riboflavin were obtained on admission (Day 1). HCY was assessed on Days 1, 7 and 11. RESULTS: HCY levels significantly declined during withdrawal. General linear models and linear regression analysis showed an influence of BAC, folate and riboflavin on the HCY levels on admission as well as on HCY changes occurring during alcohol withdrawal. No significant influence was found for thiamine, cobalamin and pyridoxine. CONCLUSIONS: These findings show that not only BAC and plasma folate levels, but also plasma levels of riboflavin influence HCY plasma levels in alcohol-dependent patients.

[Antipsychotic Polypharmacy in the Treatment of Patients with Schizophrenia in Nine Psychiatric Hospitals of the Landschaftsverband Rheinland, Germany]. / Antipsychotische Polypharmazie in der Behandlung von Patientinnen und Patienten mit Schizophrenie am Beispiel von neun psychiatrischen Fachkliniken des Landschaftsverbandes Rheinland.

BACKGROUND: Antipsychotics are the cornerstone in the treatment of schizophrenia and are primarily recommended as monotherapy by evidence-based guidelines. Nevertheless, antipsychotic polypharmacy (APP) is prevalent in routine practice and APP is also used as a quality indicator since 2016 in quality management programs. OBJECTIVE: Based on routine data of nine psychiatric hospitals of the Landschaftsverband Rheinland (LVR)/Germany the prevalence of APP was determined and correlated with factors of routine healthcare in order to monitor the adoption of APP and to discuss its feasibility as a quality indicator. MATERIALS AND METHODS: All cases with schizophrenia (ICD-10 F20.x; ≥ 18 years) discharged between June 1st, 2016, and June 1st, 2017, (in-patient and day clinic) were extracted from an established research database shared by all nine hospitals and analyzed regarding APP prevalence at the time of discharge. RESULTS: Based on 6,788 cases, the prevalence of APP was 55.5 % with an average of 2.4 antipsychotics (SD = 0.6) administered simultaneously. In multivariate analyses, significant predictors for APP were: gender (male > female), the number of days in hospital (long > short), involuntary treatment (no > yes) and the location of the hospital. CONCLUSIONS: We found a high proportion of polypharmacy in inpatient schizophrenia patients and significant differences between hospitals. The use of the results as a quality indicator (criteria ≥ 2 antipsychotics) remains dependent on the background of the individual treatment courses, which cannot be adequately represented by the existing routine data. The LVR has been using the quality indicator of ≥ 3 antipsychotics since 2018, which is discussed as a more appropriate approach for future evaluations.

Altered striatal reward processing in abstinent dependent cannabis users: Social context matters.

Public perception of cannabis as relatively harmless, alongside claimed medical benefits, have led to moves towards its legalization. Yet, long-term consequences of cannabis dependence, and whether they differ qualitatively from other drugs, are still poorly understood. A key feature of addictive drugs is that chronic use leads to adaptations in striatal reward processing, blunting responsivity to the substance itself and natural (non-drug) rewards. Against this background, the present study investigated whether cannabis dependence is associated with lasting alterations in behavioral and neural responses to social reward in 23 abstinent cannabis-dependent men and 24 matched non-using controls. In an interpersonal pleasant touch fMRI paradigm, participants were led to believe they were in physical closeness of or touched (CLOSE, TOUCH) by either a male or female experimenter (MALE, FEMALE), allowing contextual modulation of the perceived pleasantness and associated neural responses. Upon female compared to male touch, dependent cannabis users displayed a significantly attenuated increase of pleasantness experience compared to healthy controls. Controls responded to female as compared to male interaction with increased striatal activation whereas cannabis users displayed the opposite activation pattern, with stronger alterations being associated with a higher lifetime exposure to cannabis. Neural processing of pleasant touch in dependent cannabis users was found to be intact. These findings demonstrate that cannabis dependence is linked to blunted striatal processing of non-drug rewards and suggest that these alterations may contribute to social processing deficits.

Range of therapeutic prothipendyl and prothipendyl sulfoxide concentrations in clinical blood samples.

Due to a lack of reference blood concentrations in the literature, the forensic evaluation of prothipendyl findings in blood samples is difficult. Interpretations with regard to the assessment of blood concentrations as well as an estimation of the ingested prothipendyl amounts were often vague. To describe a concentration range in clinical samples, prothipendyl and prothipendyl sulfoxide concentrations were determined in serum samples of 50 psychiatric patients receiving 40 mg, 80 mg, or 160 mg doses of prothipendyl. The analyses of prothipendyl and prothipendyl sulfoxide were carried out using validated methods of high performance liquid chromatography coupled to triple quadrupole mass spectrometry (LC-QQQ-MS), respectively. 40 mg doses caused average prothipendyl serum concentrations of 18.0 ng/mL (1 hour after intake) and 7.9 ng/mL (10.5 hours after intake), while 80 mg doses caused averages of 42.6 ng/mL and 15.2 ng/mL at the mentioned times of sampling. Irrespective of the given dose, prothipendyl concentrations below 30 ng/mL were observed in 80% of the patient samples taken 1 hour after ingestion as well as in 90% of the samples collected 10.5 hours after administration. Serum concentrations of the Phase I metabolite prothipendyl sulfoxide averaged 4.3 ng/mL (1 hour after intake) and 3.6 ng/mL (10.5 hours after intake). Possible drug-drug interactions regarding absorption and metabolism of prothipendyl are discussed. Results of the herein presented study are useful for the interpretation of analytical prothipendyl findings in forensic toxicology. The utility of the described concentration range is demonstrated by discussing two death cases involving prothipendyl findings.

Altered orbitofrontal activity and dorsal striatal connectivity during emotion processing in dependent marijuana users after 28 days of abstinence.

RATIONALE: Intact cognitive and emotional functioning is vital for the long-term success of addiction treatment strategies. Accumulating evidence suggests an association between chronic marijuana use and lasting alterations in cognitive brain function. Despite initial evidence for altered emotion processing in dependent marijuana users after short abstinence periods, adaptations in the domain of emotion processing after longer abstinence remain to be determined. OBJECTIVE AND METHODS: Using task-based and resting state fMRI, the present study investigated emotion processing in 19 dependent marijuana users and 18 matched non-using controls after an abstinence period of > 28 days. RESULTS: Relative to the control subjects, negative emotional stimuli elicited increased medial orbitofrontal cortex (mOFC) activity and stronger mOFC-dorsal striatal and mOFC-amygdala functional coupling in dependent marijuana users (p < 0.022, FWE-corrected). Furthermore, mOFC-dorsal striatal functional connectivity was increased at rest in marijuana users (p < 0.03, FWE-corrected). Yet, processing of positive stimuli and subjective ratings of valence and arousal were comparable in both groups. CONCLUSIONS: Together, the present findings provide the first evidence for persisting emotion processing alterations in dependent marijuana users. Alterations might reflect long-term neural adaptations as a consequence of chronic marijuana use or predisposing risk factors for the development of marijuana dependence.

Gabapentin's acute effect on mood profile -- a controlled study on patients with alcohol withdrawal.

RATIONALE: Delayed beneficial effects of gabapentin on mood were frequently reported in various patient populations. This is the first controlled study which addressed acute effects of gabapentin on mood. METHODS: Analysis of the German version of Profile of Mood States (POMS) throughout a randomised placebo-controlled, double-blinded study of gabapentin on acute alcohol withdrawal [Bonnet, U., Banger, M., Leweke, F.M., Specka, M., Müller, B.W., Hashemi, T., Nyhuis, P.W., Kutscher, S., Burtscheidt, W., Gastpar, M. 2003. Treatment of acute alcohol withdrawal with gabapentin -- results from a controlled two-center trial. J Clin Psychopharmacol 23, 514-519]. In addition, subjective severity of alcohol withdrawal was determined by the Essen Self-Assessment of Alcohol Withdrawal Scale (ESA) to control effects of concurrent withdrawal on POMS. Ratings were performed at intake (baseline), day 1 (study medication 400 mg q.i.d.), day 2 (study medication 400 mg q.i.d.) and day 7 (no study medication). RESULTS: Analyses could be performed on 46 out of 59 randomised subjects. Within the first two days of the study, a significant stronger increase in the POMS-vigour subscore occurred in the gabapentin group. A subgroup analysis suggests that gabapentin's effect on vigour largely results from a stronger improvement of vigour in a small group of 11 patients with co-morbid mild depression (according to ICD-10: dysthymia or depressive adjustment disorder). There were no significant differences between the treatment groups regarding the other POMS-subscores (dejection, fatigue, anger) ruling out an overall fast effect on mood. Moreover, ESA-measures were not significantly altered indicating a missing effect of 400 mg gabapentin q.i.d. on acute alcohol withdrawal itself. After tapering off study medication, no more significant differences between gabapentin and placebo group were observed on vigour, strongly suggesting that the initial effect results from a pharmacological gabapentin action. CONCLUSION: Gabapentin selectively accelerated the improvement of the vigour-subscore of patients with acute alcohol withdrawal within 48 h. This effect was independent from the subjective severity of withdrawal and especially marked in patients with co-morbid mild depression.

Alcohol abuse and cigarette smoking are associated with global DNA hypermethylation: results from the German Investigation on Neurobiology in Alcoholism (GINA).

Recent studies have shown that smoking and alcoholism may be associated with altered DNA methylation and that alcohol consumption might induce changes in DNA methylation by altering homocysteine metabolism. In this monocenter study, we included 363 consecutive patients referred for hospitalization for alcohol detoxification treatment. Blood samples were obtained on treatment days 1, 3, and 7 for measurement of global DNA methylation in leukocytes by liquid chromatography tandem mass spectrometry. Genomic DNA was used for genotyping the following seven genetic variants of homocysteine metabolism: cystathionine beta-synthase (CBS) c.844_855ins68, dihydrofolate-reductase (DHFR) c.594 + 59del19bp, methylenetetrahydrofolate-reductase (MTHFR) c.677C > T and c.1298A > C, methyltetrahydrofolate-transferase (MTR) c.2756A > G, reduced folate carrier 1 (RFC1) c.80G > A, and transcobalamin 2 c.776C > G. Multivariate linear regression showed a positive correlation of global DNA methylation with alcohol consumption and smoking on day 1 of hospitalization. DNA methylation was not correlated with homocysteine or vitamin plasma levels, nor with the tested genetic variants of homocysteine metabolism. This suggests a direct effect of alcohol consumption and smoking on DNA methylation, which is not mediated by effects of alcohol on homocysteine metabolism.

[The qualified-detoxification-of-alcoholics procedure--in light of the development of guidelines for the treatment of substance-related disorders]. / Die "Qualifizierte Entgiftung Alkoholkranker"--Im Lichte der Entwicklung von Behandlungsleitlinien für substanzbezogene Störungen.

The qualified-detoxification-of-alcoholics procedure encompasses the diagnosis and treatment of ethanol intoxication, the states of complicated and uncomplicated withdrawal, addiction as the underlying disease and the consequences of heavy drinking. There is empirical evidence that treatment periods of 3 weeks for inpatients are efficient and cost-effective and there are indications that the shorter treatment periods enforced by health insurance companies may lead to rapid relapse and readmission and hence to longer total treatment times and higher costs.

Can reinforcement-based interventions to reduce drug use successfully be adapted to routine opioid maintenance treatment?

INTRODUCTION: Comorbid substance related disorders are a major health problem for patients in opioid maintenance treatment (OMT). It was investigated whether a reinforcement scheme adapted to the regulatory and financial restrictions of routine treatment reduces concomitant drug use. METHODS: OMT patients from 7 clinics who were using cocaine, benzodiazepines, heroin or amphetamines were randomly allocated to either treatment as usual (n = 64) or treatment with an additional escalating reinforcement scheme (n = 72) in which a patient's number of weekly take-home dosages was increased after 1, 4, 8 and 12 consecutive weeks with drug-free urine specimens. Trial duration was 26 weeks. RESULTS: Completion rates were 64% for controls and 62.5% in the experimental group. Mean number of drug-free weeks was 11.3 (SD 8.5) for the control group and 9.8 (8.9) for the experimental group (p = 0.30). CONCLUSION: The intervention was not effective compared to routine treatment. Additional features might be necessary to achieve an effect, e.g. a higher frequency of urine sampling or use of other reinforcers. It has to be further investigated how interventions which have been proven effective in experimental studies can successfully be adapted to routine care conditions.

[The visit at home by a social worker of a psychiatric outpatient clinic]. / Der Hausbesuch im Kontext der aufsuchenden Sozialarbeit einer psychiatrischen Institutsambulanz.

OBJECTIVE: The high rank of social work in context with psychiatric treatment of in-patients is generally accepted. The value of social work and here especially the visit at home by the social worker has hardly been examined up to now. METHOD: In the article first of all the method of visits at home is presented. Furthermore all visits at home by a female social worker of an outpatient clinic over a period of three years are retrospectively evaluated. RESULTS: In connection with 28 patients (54 +/- 14 years old) 218 visits - in total - were carried out. It is remarkable that - apart from one case - the patients were at home and the social worker was admitted to their private rooms. By far most frequently the emphasis of the visit at home was assigned to the solution of actual problems within the framework of a long-term socio-therapeutic process. CONCLUSIONS: In further discussion it will be crucial to work out indications and contraindications as well as directives for technical execution and - if necessary - to develop differential indications for different types of visits at home for different groups of patients.

Concomitant endocrine and immune alterations during alcohol intoxication and acute withdrawal in alcohol-dependent subjects.

Although both alcohol intoxication and withdrawal have been demonstrated to produce significant endocrine alterations, no data exist on the effects of acute withdrawal on immune functions. Therefore, the current study investigated the effect of alcohol intoxication and acute withdrawal on plasma cortisol, prolactin and catecholamines, and blood leukocyte subset distribution in alcohol-dependent subjects. Nine male alcoholics admitted to the university clinic for alcohol dependence and 9 age-matched controls participated in the study. Blood was drawn from the alcohol-dependent subjects at 10:30 a.m. on day 0 (chronic alcohol intoxication), at the same time during acute alcohol withdrawal (day 1) and following the resolution of acute withdrawal (day 7). Blood was drawn from age- and gender-matched healthy control subjects at the corresponding time points. Plasma was then analyzed for hormone concentrations and blood examined for leukocyte subsets by flow cytometry. Alcohol-dependent patients displayed significantly elevated plasma cortisol during intoxication and withdrawal, which decreased to control levels following resolution of acute withdrawal. Small elevations of plasma prolactin and catecholamines were also observed during intoxication. Furthermore, alcohol-dependent subjects showed reduced absolute numbers of CD4(+) and CD8(+) T cells and natural killer cells compared with healthy controls across all time points. In contrast, although monocyte numbers were lower in alcohol-dependent patients during intoxication, acute alcohol withdrawal increased the number of monocytes in patients. Thus, alcohol dependence produces a general suppression of leukocyte subset populations in blood. However, resolution of acute alcohol withdrawal is associated with a return of plasma cortisol to control levels, and a concomitant increase in peripheral blood monocyte numbers.

Treatment of acute alcohol withdrawal with gabapentin: results from a controlled two-center trial.

A few case reports and data from animal experiments point to a possible efficacy of gabapentin (GP) in the treatment of alcohol withdrawal syndrome (AWS). Because of ethical considerations, the efficacy of GP in acute AWS was tested in an add-on fashion to clomethiazole (CLO). Given that the symptom-triggered amount of CLO required to limit AWS within the first 24 hours is related to the severity of AWS, we tested this amount of CLO during placebo (P) or GP (400 mg qid) under double blind, randomized conditions. Sixty-one patients (P = 29/GP = 32) suffering from alcohol dependence (ICD-10) and without any other psychiatric condition or psychotropic medication were included. The groups were not significantly different in baseline characteristics (eg, demographic data, severity of AWS). Both ITT and completer analyses revealed no significant differences between the groups considering the primary effectiveness measure: amount of CLO required in the first 24 hours (P = 6.1 +/- 5.4/GP = 6.2 +/- 4.7 capsules). In addition, premature discontinuations (P = 3/GP = 2) and decreases in Mainz Alcohol Withdrawal Scores were not significantly different in the first 48 hours of AWS (secondary effectiveness measures). Tolerability of combined CLO/GP was studied throughout the whole treatment comprising a 5-day lasting reduction part subsequent to the first 48 hours. Throughout the whole 7-day treatment a total of 5 and 2 patients dropped out and 6 and 5 patients reported adverse clinical events in the P and GP groups, respectively. All together, GP (400 mg qid) was no better than P in saving initial consumption of CLO or decreasing initial Mainz Alcohol Withdrawal Scores suggesting that GP was ineffective in the management of acute AWS in this model. The combination of GP and CLO was safe.