Pipamperone Population Pharmacokinetics Related to Effectiveness and Side Effects in Children and Adolescents

Background: Pipamperone is a frequently prescribed antipsychotic in children and adolescents in the Netherlands, Belgium, and Germany. However, pediatric pharmacokinetics and the relationship with side effects and efficacy are unknown. Currently, divergent pediatric dosing recommendations exist. Objectives: The objective of this study was to describe the population pharmacokinetics of pipamperone in children and adolescents; to correlate measured and predicted pipamperone trough concentrations and predicted 24-h area under the curves with effectiveness, extrapyramidal symptoms, and sedation; and to propose dose recommendations based on simulations. Methods: Pipamperone concentrations were collected from Dutch pediatric patients in a prospective naturalistic trial (n = 8), and German pediatric patients in a therapeutic drug monitoring service (n = 22). A total of 70 pipamperone concentrations were used to develop a population pharmacokinetic model with non-linear mixed-effects modeling (NONMEM®). Additionally, an additional random sample of 21 German patients with 33 pipamperone concentrations from the same therapeutic drug monitoring service was used for external validation. Pharmacokinetic parameters were related to clinical improvement, sedation, and extrapyramidal symptoms. Simulations were performed to determine optimal dosages. Results: In a one-compartment model, the apparent volume of distribution was 416 L/70 kg and the apparent clearance was 22.1 L/h/70 kg. Allometric scaling was used to correct for differences in bodyweight. The model was successfully externally validated. The median [25th–75th percentile] measured pipamperone trough concentrations were numerically higher in responders (98.0 µg/L [56.0–180.5 µg/L]) than in non-responders (58.0 µg/L [14.9–105.5 µg/L]), although non-significant (p = 0.14). A twice-daily 0.6-mg/kg dosage was better than a fixed dosage to attain the concentration range observed in responders. Conclusions: Our findings suggest that pipamperone therapeutic reference ranges may be lower for children with behavioral problems than recommended for adults with psychotic symptoms (100–400 µg/L). When dosing pipamperone in children and adolescents, bodyweight should be taken into account

Statistics versus livelihoods: questioning Rwanda’s pathway out of poverty

Recent statistics indicate that poverty in Rwanda decreased impressively between 2006 and 2014. This seems to confirm Rwanda’s developmental progress. This article however argues for a more cautious interpretation of household survey data. The authors contrast macro-level statistical analysis with in-depth field research on livelihood conditions. Macro-economic numbers provide interesting information, however differentiated evidence is required to understand how poverty ‘works’ in everyday life. On the basis of the Rwandan case study, the authors conclude that because of the high political stakes of data collection and analysis, and given that relations of power influence the production of knowledge on poverty, cross-checking is crucial

The European NEAT program: an integrated approach using acamprosate and psychosocial support for the prevention of relapse in alcohol-dependent patients with a statistical modeling of therapy success prediction.

Multicenter, prospective study in five European countries to observe outcome in alcohol misusers treated for 24 weeks with acamprosate and various psychosocial support techniques, within the setting of standard patient care. 1289 patients were recruited,543 (42.1%)patients were observed for the full 24-week period. The overall proportion of cumulative abstinence days was 0.48. Multiple physical and psychiatric comorbidities and a history of drug addiction were negatively correlated with outcome, as were, to a lesser extent, multiple previous episodes of detoxification, unemployment, and living alone. Older age and stable employment were positively associated with outcome. The difference in the unadjusted proportion of cumulative abstinence days between countries was significant (p< 0.001). Overall, outcome was not influenced by the nature of the psychosocial support provided. Adverse events were generally mild, with gastrointestinal disorders, which occurred in 21.5% of patients.Multicentre, prospective study dans 5 pays Europeens pour observation de patients alcooliques traités sur 24 semaines avec acamprosate et des psychotherapies variées. 1289 patients ont été recrutés,543 (42.1%)patients ont terminés normalement au bout des 24 semaines. La proportion de cumulative abstinence days CAD fut de 0.48. La difference dans la proportion de CAD ajustée fut significative entre les pays(p< 0.001). Il semble que le devenir ne soit pas dépendant du choix de la psychothérapie

Double-blind clinical study comparing alprazolam and doxepin in primary unipolar depression

The therapeutic effect and safety of alprazolam and doxepin were studied in 126 outpatients suffering from primary unipolar depression. The 6-week study was double-blind with a random allocation of treatment. Patients were treated with a flexible dose of 1.0-4.5 mg of alprazolam and 50-225 mg of doxepin per day. The mean final doses were 2.7 mg for alprazolam and 137.5 mg for doxepin. The results indicate that alprazolam and doxepin were equally efficacious. The incidence of side-effects was lower in the alprazolam treatment group. © 1984