Rüdiger Holzbach

Leptin: a modulator of alcohol craving?

BACKGROUND Leptin has been shown to regulate food intake and energy expenditure. Because leptin acts via regulation of appetite, we studied the hypothesis that suggests leptin modulates craving for alcohol as well. METHODS We studied leptin plasma concentrations (RIA) both in alcoholic subjects during inpatient detoxification (day 1: n = 78, day 14: n = 60) and in healthy control subjects (n = 30). To rule out interference with the activation of the HPA axis during alcohol withdrawal, we also evaluated cortisol plasma levels (RIA). RESULTS We found plasma leptin and cortisol elevated at onset of withdrawal, decreasing significantly up to day 14. Leptin (and the body-mass corrected ratio leptin/BMI) was highly correlated with self-rated craving. No correlations of craving with cortisol and BMI were observed. CONCLUSIONS We suggest that leptin may modulate withdrawal-induced craving in alcoholic subjects.

Efficacy and Side-Effects of Clozapine: Testing for Association with Allelic Variation in the Dopamine D4 Receptor Gene

Genetic factors are supposed to play a major role not only in the etiology of psychiatric disorders but also in individual response to medications. To test the hypothesis that inter-individual differences in response to clozapine and the occurrence of side-effects might be influenced by variations in the dopamine D4 receptor gene, we examined frequencies of four known polymorphic sites affecting protein structure in the dopamine D4 receptor gene in 149 patients with schizophrenia or schizoaffective disorder treated with clozapine. The D4 polymorphisms included a 13-base pair deletion, which through a frameshift leads to a truncated nonfunctional receptor protein. There were, however, no significant differences in genotype counts between responders and non-responders. Furthermore, no side-effect was found to be associated with genetic variants of the dopamine D4 receptor.

Objective and subjective efficacy as well as tolerability of olanzapine in the acute treatment of 120 patients with schizophrenia spectrum disorders.

The aim of the present study was to evaluate the objective and subjective efficacy as well as tolerability of olanzapine in acute treatment of schizophrenia spectrum disorders under naturalistic non-selective conditions. Inpatients with schizophrenia spectrum disorders, consecutively admitted over an 18-month period, treated with olanzapine, were included. Diagnoses were made according to ICD-10 criteria based on repeated clinical assessments. Efficacy and tolerability of olanzapine were assessed at baseline and at the end of inpatient acute treatment including Positive and Negative Symptom Scale (PANSS), Clinical Global Impression, subjective assessments, UKU and biological investigations. One hundred and twenty non-selected patients who met ICD-10 criteria for schizophrenia (73%), schizophreniform disorder (14%) or schizoaffective disorder (13%) were treated with olanzapine 15.3±5.2 mg/day. Baseline severity (PANSS total mean score 102.2) was higher compared to various admittance studies (PANSS total mean score 86–90). In 32% of patients (n=38), olanzapine treatment was discontinued, mainly because of inefficacy for positive (89%, n=34) and/or negative (95%, n=36) symptoms and/or because of adverse events (37%, n=14). Response rates as improvement in PANSS total score (after ≥3 weeks of treatment) of ≥20%, 30% or 40% were 68%, 55% and 35%, respectively. Response rates in post-hoc defined treatment resistant patients were not significantly different from non-refractory patients. Sedation (26%) was the most common side-effect, followed by weight gain (22%). With regards to subjective efficacy, 30% of the patients were not satisfied with the efficacy of olanzapine, while only 6% of the patients reported a not satisfying subjective tolerability. According to duration of olanzapine treatment, the results for patients, who remained in hospital, revealed a faster increase of weight compared to admittance studies (7 kg in 14 weeks versus 7 kg in 38 weeks). Olanzapine has been found to be effective and tolerable, also under naturalistic acute treatment conditions. Compared to previous double-blind admittance studies, patients had a higher severity of illness at entry and a lower ≥40% PANSS total score response rate. By contrast to previous results, mean dose of olanzapine was similar for multiple- and first-episode patients, and weight gain was more severe. The results underline the need of Phase IV studies for the assessment of clinical antipsychotic efficacy and tolerability.

Comparing the efficacy of atypical antipsychotics in open uncontrolled versus double-blind controlled trials in schizophrenia

AbstractObjective. Due to methodological reservations, open clinical trials investigating efficacy and tolerability of antipsychotic agents are often regarded with doubt. However, there are nearly no studies comparing findings of controlled double-blind with those of open trials. The aim of this study was to investigate whether results of open and double-blind approaches differ and thereby gain information about the validity of open trials. Methods. After literature research, three atypical antipsychotic agents were identified for which at least three open and double-blind trials existed that met the inclusion criteria and from which either the reduction of the Brief Psychiatric Rating Scale (BPRS)- or Positive and Negative Symptom Scale (PANSS) scores or the response rate could be determined. Results. There were no differences in the reduction of the BPRS- or PANSS scores or in the response rates for all three antipsychotic agents between open and double-blind trials. Conclusions. Although double-blind controlled studies are essential in the investigation of new compounds, results of methodologically well-performed open studies are valid and deserve more attention. Preceding open trials may help in the design of double-blind studies.

[Substance-abuse related emergencies--illegal drugs, part I].

For the first time since the year 2000 the number of death due to substance abuse of illegal drugs has increased in Germany in 2007 (+8 % compared to 2006). Emergency situations due to drug abuse are frequent, particular in big cities. They may be, however, difficult to diagnose and/or treat for an emergency physician on scene because of a lack of diagnostic tools, the local and personal surroundings, and the unknown number and nature of drugs. Many drug intoxications must be considered suicidal. On the other hand, drug intoxications may mask (other) life-threatening conditions. Emergency situations due to withdrawal offer the possibility to motivate patients to take advantage of specialist-guided abstinence programs.

Alcohol-related disorders in the preclinical medicine

Alcohol is the most frequently abused drug in Germany. Approximately 50.000 individuals die annually due to alcohol-related disorders. Emergency situations due to alcohol intoxications, abuse or dependence are frequent reasons for calls for emergency physicians and paramedics. Agitation, suicidal intent, trauma and a multitude of degenerative and other somatic disorders may further complicate diagnosis and treatment on scene. The motivation of patients to participate in withdrawal programs should be built and strengthened already in emergency medicine.