Current Findings and Mechanisms of Action of Disulfiram in the Treatment of Alcohol Dependence.

As an alcohol-aversive agent, disulfiram occupies an exceptional position in the pharmacological relapse prevention of alcohol dependence. In contrast to anti-craving drugs, disulfiram does not modulate neurobiological mechanisms of addiction, but rather works by producing an aversive reaction when combined with alcohol. Therapeutic and adverse effects are therefore closely related: On the one hand, the aversiveness of the disulfiram ethanol reaction has the potential to support abstinence in a subgroup of alcohol-dependent patients, while on the other hand it becomes a health threat if the patient fails to maintain complete abstinence. The exceptional position of disulfiram is also related to the role that expectations play in the mediation of therapeutic effects. These are not determined by the pharmacological effects or the actual occurrence of a disulfiram-ethanol reaction, but are attributable to patient awareness that the drug was consumed and the corresponding anticipation of an aversive reaction if combined with alcohol. This is in line with the findings of a recent meta-analysis that only showed significant effects for disulfiram in open-label trials. The authors of the meta-analysis conclude that due to expectations induced in both the treatment and placebo groups, blinded studies are incapable of distinguishing a difference between groups. The mediation of therapeutic effects through expectation has a number of consequences for clinical practice and future research on disulfiram.

Impairment of inhibitory control in response to food-associated cues and attentional bias of obese participants and normal-weight controls.

OBJECTIVE: Starting from a model of impaired response inhibition and salience attribution for addictive behaviour we investigated whether obese participants show a greater impairment of inhibitory control in response to food-associated cues compared with neutral stimuli and whether this is seen in normal-weight control subjects. In addition, we questioned whether an attentional bias towards food-associated cues can be observed in an early stage of information processing. DESIGN: Control-group study including the administration of behavioural tasks (that is, go/no-go task with food-associated and neutral words, visual dot probe task with food-associated and neutral pictures) and self-reported measures of eating behaviour and impulsivity. RESULTS: Although self-reported measures indicated disinhibition of eating behaviour of obese patients, we found that food-associated stimuli induced an impairment of inhibitory control in both obese participants as well as normal-weight controls. Results from the visual dot-probe task indicated that food-associated cues did not modulate attention allocation in a very early stage of information processing, which suggests that the incentive salience of food-associated stimuli might be lower than that of drug-associated cues. CONCLUSION: These findings are not in line with hypotheses derived from models of addictive behaviour and call into question that an impairment of inhibitory control in response to food-associated cues and salience attribution might be at the core of obesity. Future studies using larger sample sizes and refined experimental procedures are warranted to further investigate mechanisms controlling food intake in obesity.

[What can addiction research contribute towards the understanding of obesity?]. / Beitrag der Suchtforschung zum Verständnis der Adipositas.

Recent research suggests similarities between obesity and addictive disorders on both phenomenological and neurobiological levels. In particular neuro-endocrine and imaging studies have shown a close link between homeostatic regulation involved in appetite regulation and regulation of motivation and reward expectancy, which are of special impact for addictive disorders. Based on findings on the neurobiology of reinforcement processes and on the role of classical conditioning in addiction, new interventions for prevention and treatment were developed that offer the opportunity for transfer to the treatment of obesity. A first step may be testing psychotherapeutic and pharmacotherapeutic interventions, which primarily target motivational processes. The relevance of this topic for general psychiatry is reflected by the fact that including obesity in the psychiatric chapters of disease classification systems is currently being discussed.

[Carbamazepine intoxication. Complication of alcohol detoxification with combined carbamazepine and tiapride]. / Carbamazepin-Intoxikation. Komplikation der Kombinationsbehandlung aus Carbamazepin und Tiaprid zur Alkoholentgiftung.

The advantages of alcohol detoxification treatment with combined carbamazepine and tiapride compared to benzodiazepines or clomethiazole is a lower level of sedation and lack of addictive potential. We report a case of carbamazepine intoxication with serum levels up to 19 mg/l in an otherwise healthy 45-year-old alcohol-dependent male after treatment with 600 mg carbamazepine and 600 mg tiapride per day. Medication was discontinued immediately and a purgative was administered. We were able to combat the intoxication but the assumed good tolerance of the combined treatment with carbamazepine and tiapride for alcohol detoxification still has to be proven.

Scheme-based benzodiazepine detoxification with oxcarbazepine -- a case report.

We attempted to evaluate the tolerability and efficacy of the antiepileptic drug oxcarbazepine in benzodiazepine detoxification, by observing several cases. Detoxification followed a predefined dosage scheme. All patients detoxified with oxcarbazepine completed the withdrawal successfully, without withdrawal symptoms. The administration of oxcarbazepine according to the scheme proved to be tolerable. The dosage was sufficient. Though uncontrolled case observations must be interpreted with caution, oxcarbazepine appears to be a promising drug in inpatient benzodiazepine withdrawal. It should be examined in further randomized placebo-controlled studies including long-term follow-ups.