摘要:

In pharmacotherapy, overtreatment may be defined as an excessive drug load (that is, excessive drug dosages or unnecessary polypharmacy) leading to a suboptimal risk-to-benefit ratio. The risk of overtreatment in the pharmacological management of epilepsy is substantial and may have serious consequences in terms of a greater incidence and severity of adverse effects. These effects can range from subtle CNS impairment to overt toxic effects, including teratogenicity. Overtreatment also causes increased treatment costs and may even lead to a paradoxical deterioration in seizure control. The prevention and correction of overtreatment requires a thorough understanding of the situations and mechanisms that lead to inappropriate prescribing of antiepileptic drugs. These include initiating treatment in conditions where it is not indicated (for example, long-term prophylaxis after head trauma or supratentorial surgery in seizure-free patients), use of excessively fast titration rates, prescription of excessively high initial target dosages, failure to consider conditions associated with reduced dosage requirements (for example, old age or comorbidities associated with impaired drug clearance), and failure to consider the dose-response characteristics of the selected drug. Many patients whose seizures do not respond to the initially prescribed medication can be optimally managed by switching to monotherapy with an alternative agent; premature use of combination therapy represents another common form of overtreatment. Overtreatment may also result from a failure to adjust the dosage to prevent or compensate for adverse pharmacokinetic or pharmacodynamic drug interactions, and from a failure to reduce drug load in patients who have not benefited from high dosages or polypharmacy. While the measurement of drug concentrations can aid in minimising adverse effects, there is also a danger of overtreatment resulting from inappropriate interpretation of drug concentration data. Continuation of drug therapy in seizure-free patients in whom the risk-benefit ratio is in favour of gradual withdrawal may also be regarded as overtreatment.Tailoring therapy to the needs of the individual patient is the key to the successful management of epilepsy. Even though the importance of complete seizure control cannot be overemphasised, no patient should be made to suffer more from the adverse effects of treatment than from the manifestations of the seizure disorder.

ISSN:1172-7047    

出版商:ADIS    

年代:2005

数据来源: ADIS

摘要:

Multiple sclerosis (MS) has been recognised as a disease since the mid-19th century. The delineation of its CNS pathology, revealing the presence of inflammatory demyelination and relative sparing of axons, was originally interpreted as evidence of infection. Despite many studies, a primary infectious aetiology of MS has not been found. However, the occurrence of acute demyelinating disease following a variety of infections and vaccinations, leading to MS in about a third of cases, provides evidence for the existence of an auto-allergic pathogenesis for the disease.Improved understanding of the role of the blood-brain barrier in protecting the CNS, and the mechanisms by which cells gain entry into the brain and spinal cord has advanced the understanding of MS. Evidence of the central role of the adhesion molecule α4β1-integrin (very late activation antigen-4 [VLA-4]) for lymphocytes in endothelial transmigration into the CNS specifically, has provided a major insight into the pathogenesis of human demyelinating disease and its experimental model, experimental autoimmune encephalomyelitis (EAE). This finding has led to a new window of therapeutic opportunity in MS.Monoclonal antibodies to VLA-4 abrogate the development of EAE in sensitised animals and may actually reverse its clinical and pathological findings in manifest disease. Natalizumab, one such monoclonal antibody, which is administered intravenously, has been found to be a promising agent in the treatment of MS. Although single doses produced no improvement in the speed or quality of recovery from acute exacerbations of MS in a phase II trial, long-term administration (in phase II and phase III trials) have produced significant benefits with results showing both a marked reduction in the risk of new magnetic resonance imaging lesions and a significant reduction in the risk of exacerbations within 2 months of the initiation of therapy. Phase III double-blinded controlled trials have provided additional evidence of safety and a favourable impact on exacerbation rates over the 1 year of administration. Unfortunately, the success of natalizumab has been curtailed by three cases of progressive multifocal leukoencephalopathy, which have prompted the manufacturer to voluntary withdraw the drug from the market. An independent review board is currently investigating the safety of the drug to determine whether it should return to the market.The demonstration that selective modulation (blocking) of the adhesion molecule VLA-4 by natalizumab in MS, resembling that observed in experimental disease, represents a major advance in rational therapy.

ISSN:1172-7047    

出版商:ADIS    

年代:2005

数据来源: ADIS

摘要:

Autism is a disorder characterised by abnormalities in language and social development, and repetitive behaviours. Antipsychotics, including haloperidol and risperidone, are the most widely studied drugs for reducing symptoms in children and adolescents with autism. When administered at relatively low dosages, antipsychotics have been shown to reduce repetitive behaviours (stereotypies) and social withdrawal, as well as a number of related symptoms, such as hyperactivity, aggression, self-abusive behaviour, temper tantrums, lability of mood and irritability. Adverse effects of antipsychotics include sedation, dizziness, increased appetite, weight gain, changes in the electrocardiogram parameters, drooling, hyperprolactinemia and a risk of drug-related dyskinesias.Other agents have been less well studied for the treatment of autism, but there are suggestive data regarding their safety and efficacy. Of these agents, a number have been investigated, based on theories about the aetiology of autism, including SSRIs and naltrexone, although the efficacy of these agents has been limited. Stimulant drugs have been shown to reduce hyperactivity and improve focus, but they may cause behavioural worsening, weight loss and stereotypiesde novo. Secretin is a treatment that has received much media attention after reports of efficacy from small open studies, but all controlled studies have failed to show any benefit. In autism, alternative treatments have also been used, but none have shown benefit in well-designed studies.

ISSN:1172-7047    

出版商:ADIS    

年代:2005

数据来源: ADIS

摘要:

In many countries, prescribing guidelines recommend the use of atypical or second-generation antipsychotics (SGAs) in the first-line treatment of individuals with newly diagnosed schizophrenia. This recommendation has increased the utilisation of these agents and, consequently, produced a progressive increase in the proportion of total direct costs in schizophrenia accounted for by drug therapy. In this still-evolving context of care, it becomes relevant to critically investigate the literature base on the relative cost effectiveness of each SGA in comparison with the others, the purpose being to ascertain whether the data reveal any one agent to be truly more cost effective than the others.A systematic search of economic evaluations comparing two or more SGAs yielded 19 studies meeting the inclusion criteria. Of these, 11 were retrospective database or chart review analyses, six were observational prospective or mirror-image studies, and two were randomised clinical trials. Olanzapine and risperidone were compared in 16 studies, two studies compared clozapine, olanzapine and risperidone, and one compared clozapine and risperidone.While experimental studies indicated an absence of differences among the SGAs in terms of total expenditure, database analyses found contrasting evidence. These latter studies, although susceptible to bias and confounding, should theoretically provide an added dimension, in that they are based on observations from ‘real world’ practice. However, there were too many potential threats to the validity of these analyses to draw a firm conclusion that any one agent is truly more cost effective than the others.In this uncertain situation, clinicians and policy makers should be aware that indirect evidence from independent randomised controlled trials comparing individual SGAs with haloperidol suggested similar cost effectiveness. As healthcare providers in different settings are ultimately the ones who pay for new innovations, it seems appropriate that they commission research into the cost effectiveness of SGAs.

ISSN:1172-7047    

出版商:ADIS    

年代:2005

数据来源: ADIS

摘要:

Many women experience headaches, including migraine, in association with their menstrual cycles. Although definitions vary, menstrual migraine generally refers to migraine without aura that occurs within several days prior to and several days after the onset of menses.Although menstrual migraine has been reported to be more difficult to treat than other types of migraines, there is no evidence from controlled clinical trials to support this assertion. Thus, the pharmacological treatment of menstrual migraine should be similar to that of other types of migraines, except with respect to the use of hormonal manipulations to treat menstrual migraine.Serotonin 5-HT1B/1Dreceptor agonists (triptans) are effective for the acute treatment of both menstrual and non-menstrual migraines. When used as acute therapy, a triptan should be administered early, when the headache is still mild in severity. Ideally, an acute therapy will provide rapid and complete pain relief with no disability. Some patients may require preventive therapy for menstrual migraine based on suboptimal response to an adequate trial of acute therapy. Patient diaries that record headache onset, relationship to the menstrual cycle and treatment response through three complete cycles will allow accurate prediction of the onset of menstrual migraine; this information is also needed to make decisions about timing of intermittent preventive therapy. The goals of intermittent preventive therapy are to reduce the frequency, duration and intensity of menstrual migraine attacks.Clinical studies show that triptans are effective when used as either acute therapy or as intermittent preventive therapy for menstrual migraine. Sumatriptan and zolmitriptan have been evaluated in prospective, randomised, controlled trials for acute treatment. Retrospective analyses and open-label studies also support the use of other triptans as acute therapy. In addition, sumatriptan, frovatriptan, naratriptan and zolmitriptan have been evaluated as intermittent preventive therapy in prospective studies. Thus, data from clinical studies indicate that triptans are effective for the treatment of menstrual migraine.

ISSN:1172-7047    

出版商:ADIS    

年代:2005

数据来源: ADIS

摘要:

▴ Rotigotine is a nonergolinic dopamine D3/D2/D1receptor agonist delivered via a transdermal system and has been evaluated for the treatment of idiopathic Parkinson's disease.▴ Patients with early Parkinson's disease receiving rotigotine monotherapy experienced significantly greater improvements in parkinsonian symptoms (as measured by Unified Parkinson's Disease Rating Scale scores) compared to placebo in two large, well designed clinical trials. Significant beneficial effects versus placebo were observed with the 30 and 40 cm2rotigotine patches in both trials.▴ Patients with advanced Parkinson's disease receiving rotigotine as adjunctive therapy with levodopa experienced clinically significant reductions from baseline in ‘off’ time in two well designed clinical trials. In one trial, a large placebo effect was observed, therefore, there was no significant difference between placebo and active treatment (20, 40 and 60 cm2) for this primary efficacy variable, However, a recent study found a significant (p ≤ 0.003) reduction in ‘off’ time in rotigotine 40 and 60 cm2recipients versus that in the placebo group.▴ Rotigotine was generally well tolerated in clinical trials as both monotherapy and when administered with levodopa; adverse events were generally mild or moderate in severity.Table. Features and properties of rotigotineFigure. Chemical structures of dopamine and rotigotine

ISSN:1172-7047    

出版商:ADIS    

年代:2005

数据来源: ADIS

ISSN:1172-7047    

出版商:ADIS    

年代:2005

数据来源: ADIS