摘要:

The treatment of partial seizures in children is based on the use of first generation and recently introduced antiepileptic drugs as well as nonpharmacological treatments such as the ketogenic diet, vagus nerve stimulation and surgical therapy. The present review discusses the efficacy and tolerability of different treatment options for partial seizures in childhood.Few adjunctive or monotherapy, placebo-controlled or comparative trials of the first-generation antiepileptic drugs and some of the more recently introduced antiepileptic drugs have been performed in children. This can be explained by the fact that it is only relatively recently (1989) that the International League against Epilepsy proposed that randomised, controlled trials be included among the required criteria for assessing the efficacy and tolerability of an antiepileptic agent. This led to controlled, comparative trials among older antiepileptic drugs (phenobarbital, phenytoin, carbamazepine and valproic acid), both in adults and in paediatric patients, being performed relatively ‘late’, based on when these drugs were first introduced.Carbamazepine and valproic acid may still be considered as first-line antiepileptic therapies for children with partial seizures. Phenobarbital and phenytoin are mostly considered as last choice drugs because of their adverse event profiles. The new generation of antiepileptic agents has added to the first- and second-line treatment options for paediatric partial seizures. To date, there are sufficient data to support the clinical use of some of the recently introduced antiepileptic drugs (e.g. oxcarbazepine, topiramate, gabapentin and lamotrigine) as adjunctive or first-line monotherapy. Because of the risk of visual field constriction with vigabatrin, the use of this drug is currently limited to patients refractory to other medications. Tiagabine, felbamate, levetiracetam and zonisamide have been shown to be effective in adults with partial seizures; however, at present there are not yet enough data on the efficacy of these drugs in children to support consideration of their use as either first-line or add-on therapy in this patient population, although controlled studies are expected shortly. Furthermore, the use of felbamate is considerably limited by rare, but severe, hepatic and haematological toxicity.Controlled trials for paediatric partial seizures are still lacking for the ketogenic diet and vagus nerve stimulation, though they may represent, in given patients, useful adjunctive alternative treatments for refractory partial seizures.In conclusion, further trials are needed to determine an optimal sequence of first- and second-line therapies and to establish whether other newer antiepileptic drugs merit consideration as initial therapy in children with partial seizures.

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

ObjectivesTo assess the impact of switching atypical antipsychotic treatment [fromrisperidone to olanzapine orolanzapine to risperidone] on medication use patterns and treatment costs for individuals with schizophrenia.In contrast, after switching from olanzapine to risperidone there was no significant change in treatment patterns for any of the medications assessed or in healthcare costs (mental healthcare-related or total), despite a significant decrease in mental health-related pharmaceutical costs.MethodsUsing a large, integrated medical service and pharmacy claims database, 244 individuals diagnosed with schizophrenia (International Classification of Diseases [9th revision]: 295.xx) who switched treatment from risperidone to olanzapine (n = 202) or from olanzapine to risperidone (n = 42) were identified. Changes in medication use patterns and treatment costs (1999 values) per patient from the pre- to the post-switch period were evaluated. McNemar’s tests were used to compare changes in use of antiparkinsonian, antidiabetic and antihyperlipidaemic agents and typical antipsychotics, while the Wilcoxon signed rank tests were applied to examine changes in treatment costs.In contrast, after switching from olanzapine to risperidone there was no significant change in treatment patterns for any of the medications assessed or in healthcare costs (mental healthcare-related or total), despite a significant decrease in mental health-related pharmaceutical costs.ResultsAfter switching from risperidone to olanzapine, the percentage of patients using concomitant antiparkinsonian agents and typical antipsychotics decreased significantly from 30.20% to 21.29% (p = 0.0094) and from 30.69% to 18.32% (p = 0.0006), respectively. There was no significant change in the use of antidiabetic or antihyperlipidaemic drugs. For mental health-related treatment, annualised pharmaceutical costs increased by $US1761 (from $US1829 to $US3590, p < 0.0001) but medical service costs decreased by $US3511 (from $US11 292 to $US7781, p = 0.0036), driven primarily by significantly lower emergency room care and hospital outpatient costs. This resulted in no significant change in overall mental healthcare costs. Similar results were observed with total healthcare costs.In contrast, after switching from olanzapine to risperidone there was no significant change in treatment patterns for any of the medications assessed or in healthcare costs (mental healthcare-related or total), despite a significant decrease in mental health-related pharmaceutical costs.ConclusionsSwitching from risperidone to olanzapine was associated with improved medication use patterns for antiparkinsonian and typical antipsychotic agents. While both mental health and total healthcare pharmaceutical costs increased significantly, this was not associated with a significant increase in overall mental health and total healthcare costs. These outcomes, however, were not evidenced in patients switched from olanzapine to risperidone.

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Introduction and ObjectiveHaemorrheological parameters and endothelial function are known to be altered in vascular diseases, including stroke. Treatment with HMG-CoA reductase inhibitors (‘statins’) improves cerebrovascular (and cardiovascular) morbidity and mortality in patients with atherosclerosis; the beneficial effects may involve lipid-independent mechanisms. The aim of this study was to assess the short-term effect of low-dose atorvastatin on haemorrheological parameters, platelet aggregation and endothelial dysfunction in patients with chronic cerebrovascular disease and hyperlipidaemia.Adverse events were recorded at each visit. Physical examinations, haematological assessments and serum and urine chemistry assays were performed during the study.Atorvastatin significantly improved WBV after 3 months of treatment and RBC deformability after 1 month and 3 months of treatment (p < 0.05). Collagen-induced platelet aggregation was significantly decreased at 1 (p < 0.05) and 3 months (p < 0.001) compared with baseline values, despite unaltered antiplatelet therapy. vWF activity was also improved significantly (p < 0.05) after 1 month of treatment.Patients and MethodsTwenty-seven patients (mean age 61 ± 8 years) with chronic cerebrovascular disease and hyperlipidaemia were included in the study. Serum lipid levels, haemorrheological parameters (haematocrit, plasma fibrinogen levels, plasma and whole blood viscosity [WBV] and red blood cell [RBC] aggregation and deformability) and platelet aggregation were assessed at baseline and after 1 and 3 months of treatment with atorvastatin (Sortis®) 10 mg/day. von Willebrand factor (vWF) activity (a measure of endothelial function) was measured at baseline and after 1 month of treatment.Adverse events were recorded at each visit. Physical examinations, haematological assessments and serum and urine chemistry assays were performed during the study.Atorvastatin significantly improved WBV after 3 months of treatment and RBC deformability after 1 month and 3 months of treatment (p < 0.05). Collagen-induced platelet aggregation was significantly decreased at 1 (p < 0.05) and 3 months (p < 0.001) compared with baseline values, despite unaltered antiplatelet therapy. vWF activity was also improved significantly (p < 0.05) after 1 month of treatment.ResultsPlasma total cholesterol levels were reduced by a mean of 27% compared with baseline after both 1 and 3 months of treatment (p < 0.001). Low density lipoprotein-cholesterol levels were reduced by a mean of 40% and 38% (p < 0.001), respectively, after 1 and 3 months of treatment, compared with baseline values. Triglyceride levels decreased by 20% at 1 month and by 10% after 3 months (p < 0.001).Atorvastatin significantly improved WBV after 3 months of treatment and RBC deformability after 1 month and 3 months of treatment (p < 0.05). Collagen-induced platelet aggregation was significantly decreased at 1 (p < 0.05) and 3 months (p < 0.001) compared with baseline values, despite unaltered antiplatelet therapy. vWF activity was also improved significantly (p < 0.05) after 1 month of treatment.ConclusionsOur findings show that the beneficial effects of atorvastatin are complex. Besides lipid lowering, atorvastatin can improve haemorrheological parameters, platelet aggregation and endothelial dysfunction after short-term and low-dose therapy. Whether such early laboratory changes translate into clinical utility for secondary stroke prevention awaits the results of endpoint trials.

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Quetiapine (Seroquel®), a dibenzothiazepine derivative, is an atypical antipsychotic with demonstrated efficacy in acute schizophrenia. In short-term, randomised, double-blind trials, it was usually more effective than placebo, and was generally effective against both positive and negative symptoms.Overall, quetiapine (up to 750 mg/day) was at least as effective as chlorpromazine (up to 750 mg/day) and had similar efficacy to haloperidol (up to 16 mg/day) in patients with acute schizophrenia in randomised, double-blind trials; it was at least as effective as haloperidol 20 mg/day in patients with schizophrenia unresponsive or partially responsive to previous antipsychotic treatment. Improvements in overall psychopathology and positive and negative symptoms with quetiapine (up to 800 mg/day) were similar to those with risperidone (up to 8 mg/day) or olanzapine (15 mg/day) [interim analysis].Efficacy was maintained for at least 52 weeks in open-label follow-up studies in adult and elderly patients. Quetiapine improved cognitive function versus haloperidol, and depressive symptoms and hostility/aggression versus placebo.Quetiapine is well tolerated. It is associated with placebo-level incidence of extrapyramidal symptoms (EPS) across its entire dose range, appears to have a low risk for EPS in vulnerable patient groups (e.g. the elderly, adolescents or patients with organic brain disorders) and has a more favourable EPS profile than risperidone. Irrespective of dose, quetiapine, unlike risperidone and amisulpride, does not elevate plasma prolactin levels compared with placebo, and previously elevated levels may even normalise. Quetiapine appears to have minimal short-term effects on bodyweight and a favourable long-term bodyweight profile. Preliminary studies indicate that there is a high level of patient acceptability and satisfaction with quetiapine.In conclusion, quetiapine has shown efficacy against both positive and negative symptoms of schizophrenia, and has benefits in improving cognitive deficits, affective symptoms and aggression/hostility. The beneficial effects of quetiapine have been maintained for at least 52 weeks. Quetiapine was effective and well tolerated in hard-to-treat patients, and may be of particular use in these individuals. It is at least as effective as standard antipsychotics and appears to have similar efficacy to risperidone and olanzapine. The relative risk/benefit profile of quetiapine compared with other atypical antipsychotics requires further research in head-to-head trials, although quetiapine's relatively benign tolerability profile distinguishes it from other commonly used atypical agents, particularly with respect to bodyweight, EPS and plasma prolactin levels. Overall, quetiapine has an excellent risk/benefit profile and is a suitable first-line option for the treatment of schizophrenia.

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS