RESUMEN
No drug to treat vascular dementia (VaD) has yet been approved by the American or European authorities, leaving a large population of patients without effective therapy. Cerebrolysin has a long record of safety and might be efficacious in this condition. We conducted a large, multicenter, double-blind, placebo-controlled study in 242 patients meeting the criteria for VaD. The primary endpoint was the combined outcome of cognition (based on Alzheimer's Disease Assessment Scale Cognitive Subpart, Extended Version [ADAS-cog+] score) and overall clinical functioning (based on Clinician's Interview-Based Impression of Change plus Caregiver Input [CIBIC+] score) assessed after 24 weeks of treatment. Intravenous Cerebrolysin 20 mL was administered once daily over the course of 2 treatment cycles as add-on therapy to basic treatment with acetylsalicylic acid. The addition of Cerebrolysin was associated with significant improvement in both primary parameters. At week 24, ADAS-cog+ score improved by 10.6 points in the Cerebrolysin group, compared with 4.4 points in the placebo group (least squares mean difference, -6.17; P < .0001 vs placebo). CIBIC+ showed a mean improvement of 2.84 in the treatment arm and 3.68 in the placebo arm, a treatment difference of 0.84 (P < .0001 vs placebo). These findings were confirmed by responder analyses demonstrating higher rates in the Cerebrolysin group (ADAS-cog+ improvement of ≥4 points from baseline, 82.1% vs 52.2%; CIBIC+ score of <4 at week 24, 75.3% vs 37.4%; combined response in ADAS-cog+ and CIBIC+, 67.5% vs 27.0%). For Cerebrolysin, the odds ratio for achieving a favorable CIBIC+ response was 5.08 (P < .05), and that for achieving a favorable combined response was 5.63 (P < .05). Our data indicate that the addition of Cerebrolysin significantly improved clinical outcome, and that the benefits persisted for at least 24 weeks. Cerebrolysin was safe and well tolerated.
Asunto(s)
Aminoácidos/uso terapéutico , Cognición/efectos de los fármacos , Demencia Vascular/tratamiento farmacológico , Nootrópicos/uso terapéutico , Anciano , Aminoácidos/administración & dosificación , Aminoácidos/efectos adversos , Aspirina/uso terapéutico , Distribución de Chi-Cuadrado , Demencia Vascular/diagnóstico , Demencia Vascular/psicología , Método Doble Ciego , Quimioterapia Combinada , Europa (Continente) , Femenino , Humanos , Infusiones Intravenosas , Modelos Logísticos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Nootrópicos/administración & dosificación , Nootrópicos/efectos adversos , Oportunidad Relativa , Efecto Placebo , Inhibidores de Agregación Plaquetaria/uso terapéutico , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del TratamientoRESUMEN
The maintenance of the effects of Cerebrolysin, a peptidergic compound with neurotrophic activity, on cognitive performance and qEEG activity was investigated through a 12-week, open-label extension of a 4-week, randomised, placebo-controlled pilot study. Thirty-three out of 41 patients with mild-to-moderate severe probable vascular dementia (VaD) according to NINDS-AIREN participating in the double-blind phase of the study were also assessed at the follow-up visit at week 16. Patients received i.v. infusions of Cerebrolysin (10 or 30 mL) or placebo (saline) 5 days/week for 4 weeks. Neuropsychological evaluations and qEEG recordings were done at baseline, week 4 and week 16. The mean change in score from baseline in the ADAS-cog+ and the slow-to-fast qEEG power ratio (PR), used as an index of qEEG slowing, were the two primary endpoints. Correlations between changes in cognition and qEEG induced by the treatment were also assessed. At the week 16 follow-up visit, Cerebrolysin improved (p<0.05) cognitive performance at the 10-mL and 30-mL doses and reduced qEEG slowing significantly (p<0.05) at the 30-mL dose with respect to the placebo. In addition, a significant (p<0.05) positive correlation between the change from the baseline qEEG PR and ADAS-cog+ variables was observed at week 16. These results indicate a persistence of the beneficial effects of Cerebrolysin on cognition and qEEG activity in VaD patients for at least 12 weeks after treatment cessation, and they suggest the potential utility of qEEG parameters as biomarkers for VaD clinical trials.
Asunto(s)
Aminoácidos/uso terapéutico , Encéfalo/efectos de los fármacos , Cognición/efectos de los fármacos , Demencia Vascular/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Mapeo Encefálico , Método Doble Ciego , Electroencefalografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Nootrópicos/uso terapéutico , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
AIMS: To investigate the extent of acute coprescribing in primary care to children on chronic antiepileptic therapy, which could give rise to potentially harmful drug-drug interactions. DESIGN: Acute coprescribing to children on chronic antiepileptic drug therapy in primary care was assessed in 178 324 children aged 0-17 years for the year 1 November 1999 to 31 October 2000. Computerized prescribing data were retrieved from 161 representative general practices in Scotland. SETTING: One hundred and sixty-one general practices throughout Scotland. RESULTS: During the study year 723 (0.41%) children chronically prescribed antiepileptic therapy were identified. Fourteen antiepileptic agents were prescribed, with carbamazepine, sodium valproate and lamotrigine accounting for 80% of the total. During the year children on chronic antiepileptic therapy were prescribed 4895 acute coprescriptions for 269 different medicines. The average number of acute coprescriptions for non-epileptic drug therapy were eight, 11, six, and six for the 0-1, 2-4, 5-11, and 12-17-year-olds, respectively. Of these acute coprescriptions 72 (1.5%) prescribed to 22 (3.0%) children were identified as a potential source of clinically serious interactions. The age-adjusted prevalence rates for potentially serious coprescribing were 86, 26, 22, and 33/1000 children chronically prescribed antiepileptic therapy in the 0-1, 2-4, 5-11, and 12-17-year-old age groups, respectively. The drugs most commonly coprescribed which could give rise to such interactions were antacids, erythromycin, ciprofloxacin, theophylline and the low-dose oral contraceptive. For 10 (45.5%0 of the 20 children identified at risk of a potentially clinically serious adverse drug interaction, the acute coprescription was prescribed off label because of age or specific contraindication/warning. CONCLUSIONS: In primary care, 3.0% of children on chronic antiepileptic therapy are coprescribed therapeutic agents, which could give rise to clinically serious drug-drug interactions.