No abstract

Paliperidone ER (3-12 mg/day) was efficacious and tolerable in the treatment of acute mania.

Long-term efficacy and safety of paliperidone extended-release tablets (3-12 mg/day) were evaluated in pooled data from 52-week open-label extension (OLE) phases of three 6-week, placebo-controlled, double-blind (DB) trials involving 1083 schizophrenia patients. Forty-seven percent of patients completed the OLE phase. Outcome measures included Positive and Negative Syndrome Scale and Personal and Social Performance scale scores. Improvements observed on both scales in active treatment groups during the DB phases were maintained during the OLE phase. Most commonly (> or =10% patients) reported adverse events (AEs) were insomnia, headache, and akathisia. One or more serious AEs were reported by 16% of patients; two patients had a treatment-emergent AE that resulted in death (suicide). Extrapyramidal symptom-related AEs were reported by 25% of patients. Median maximum movement disorder rating scale scores indicated no severity change during the OLE. Mean (+/-SD) increase in body weight from OLE baseline to end point was 1.1+/-5.47 kg across treatment groups and there were no clinically meaningful changes for plasma glucose, insulin or lipid levels. This analysis shows that paliperidone extended-release can maintain improvements in symptoms and functioning and is generally well tolerated for up to 52 weeks in schizophrenia patients.

Background and Purpose-Early survival of patients with intracerebral hemorrhage in general is known to be most strongly dependent on the Glasgow Coma Scale score on admission. The aim of this study was to examine the factors determining functional outcome and in-hospital mortality of patients admitted with an intracerebral hemorrhage related to oral anticoagulant (OAC) use. Methods-Correlation studies and multiple logistic regression analyses were performed on data from a retrospective series of 42 patients admitted with OAC-related intracerebral hemorrhages over a 6-year period to a tertiary care center in the north of Scotland. Results-The functional outcome after an OAC-related intracerebral hemorrhage was dependent on maximum diameter of hematoma on CT scan (RϭϪ0.72, PϽ0.001) and international normalized ratio (INR) (RϭϪ0.35, Pϭ0.024). Hematoma diameter and INR were not themselves strongly correlated (Rϭ0.31, Pϭ0.099). In-hospital mortality can be predicted by the Glasgow Coma Scale score alone (R

Objective The pharmacokinetics (PK) and safety of single oral 750‐mg doses of a plant‐derived pharmaceutical formulation of highly purified cannabidiol (CBD; Epidiolex in the USA and Epidyolex in Europe; 100‐mg/mL oral solution) were assessed in healthy adults following a high‐fat/calorie meal (n = 15), a low‐fat/calorie meal (n = 14), whole milk (n = 15), or alcohol (n = 14), relative to the fasted state (n = 29). Methods Blood samples were collected until 96 hours postdose in each period and evaluated by liquid chromatography and tandem mass spectrometry. PK parameters (maximum observed plasma concentration [Cmax], area under the plasma concentration‐time curve from time zero to the last observed quantifiable concentration, area under the concentration‐time curve from time zero to infinity [AUC0‐∞], and time to maximum plasma concentration [tmax]) of CBD and its major metabolites were derived using noncompartmental analysis. Results CBD exposure increased by 3.8‐fold for AUC0‐∞ and 5.2‐fold for Cmax when CBD was administered with a high‐fat/calorie meal versus fasted. To a lesser extent, a low‐fat/calorie meal enhanced CBD exposure versus fasted with a 2.7‐fold increase in AUC0‐∞ and a 3.8‐fold increase in Cmax. Similarly, when dosed with whole milk, CBD exposure increased versus fasted by 2.4‐fold for AUC0‐∞ and 3.1‐fold for Cmax. Modest elevations in CBD exposure occurred when it was dosed with alcohol: 1.6‐fold for AUC0‐∞ and 1.9‐fold for Cmax. No clinically relevant effect of any test condition on CBD tmax or t½ versus the fasted state was apparent. The same trend was seen for the CBD metabolites, except that 7‐carboxy‐cannabidiol tmax was considerably longer when CBD was administered with alcohol (14 vs 4 hours fasted). Inter‐ and intrasubject variability in PK parameters was moderate to high during the trial. Significance CBD and metabolite exposures were most affected by a high‐fat/calorie meal. CBD exposures also increased with a low‐fat/calorie meal, whole milk, or alcohol, but to a lesser extent. CBD was tolerated, and there were no severe or serious adverse events during the trial.