摘要:

Discontinuation of antiepileptic drug (AED) treatment is a valuable option in patients with epilepsy who have been seizure free for 2 years or longer. However, the decision to withdraw AEDs must be based on a balanced view of the overall risk of seizure relapse, the factors most likely to affect that risk, and the medical, emotional and social implications of treatment continuation versus treatment withdrawal.In a critical review of 28 studies accounting for 4571 patients (2758 children, 1020 adults and a combined group of 793), most with at least 2 years of seizure remission, the proportion of patients with relapses during or after AED withdrawal ranged from 12 to 66%. Using life-table analysis, the cumulative probability of remaining seizure-free in children was 66–96% at 1 year and 61–91% at 2 years after withdrawal of AEDs. The corresponding values in adults were 39–74% and 35–57%, respectively. The relapse rate was highest in the first 12 months (especially in the first 6 months) after withdrawal and tended to decrease thereafter. Based on a previously published meta-analysis of data published up to 1992, the pooled relapse risk was 25% (95% CI 21, 30%) at 1 year and 29% (95% CI 24, 34%) at 2 years after AED withdrawal.The factors associated with a higher-than-average risk of seizure relapse included adolescent-onset epilepsy, partial seizures, the presence of an underlying neurological condition, and abnormal EEG findings at the time of AED withdrawal in children. Factors associated with a lower-than-average risk were childhood-onset epilepsy, idiopathic generalised epilepsy and – for children – a normal EEG. Selected epilepsy syndromes (e.g. benign epilepsy with centrotemporal spikes and juvenile myoclonic epilepsy) may be associated with significantly different outcomes after AED withdrawal.All these factors and their combinations may contribute to the development of guidelines for practising physicians to help them in making the best decision related to treatment discontinuation. The decision plan should also take into account social factors (driving license, job and leisure activities) as well as emotional and personal factors, and must be tailored to and discussed with the individual patient and his/her family.

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Rabbit syndrome is an antipsychotic-induced rhythmic motion of the mouth/lips, resembling the chewing movements of a rabbit. The movement consists of a vertical-only motion, at about 5Hz, with no involvement of the tongue. Usually, the involuntary movements associated with rabbit syndrome appear after a long period (in most cases months or years) of antipsychotic treatment; however, a few patients with the syndrome have had treatment histories with no antipsychotic involvement. The reported prevalence of rabbit syndrome ranges from 2.3 to 4.4% of patients treated with typical antipsychotics. There have been isolated reports of rabbit syndrome in patients treated with the atypical agents risperidone and clozapine.Patients with rabbit syndrome are most often misdiagnosed as having oral tardive dyskinesia. In such cases the key for correct diagnosis is the involvement of tardive tongue movements, which does not occur in rabbit syndrome.The treatment of rabbit syndrome is empirical, reflecting poor understanding of its neuropathology. The first step is to reduce the amount of antipsychotic treatment as much as possible. However, since, in most cases, full withdrawal of antipsychotic treatment is impossible, the syndrome cannot be completely abolished without additional measures. The next stage of treatment involves specific drugs that aim to control the syndrome. Anticholinergic drugs are the best known treatment. Rabbit syndrome does not respond to treatment with levodopa or dopamine agonists.The most striking aspect of this syndrome is its specificity. Rabbit syndrome affects only the buccal region, and within this area it involves a highly stereotyped involuntary movement. This immediately focuses attention on the basal ganglia, in particular the substantia nigra pars reticulata, which is also implicated in oral dyskinesia. Continuing neurophysiological and pharmacological research of the basal ganglia holds the key to better understanding and treatment of this syndrome in the coming years.

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Stroke is a disease of the elderly and, as a result of the expected demographic changes in many industrialised countries, its incidence is likely to increase in the future. A first-ever stroke significantly increases the likelihood of further events; thus, secondary prevention is of major importance. Only a minority of recurrent strokes can be prevented by surgical or other invasive methods, meaning that most secondary preventive measures involve drug treatment, which has become increasingly sophisticated in recent years.Ischaemic stroke constitutes the vast majority of all strokes; effective secondary prevention depends on a variety of factors, of which the correct classification in terms of subtypes and aetiological mechanisms is a pivotal prerequisite, as is the assessment of the patient’s cardiovascular risk profile. In addition to the evaluation of pathomechanisms, stratification of subtypes of brain infarction is mainly based on morphology seen with brain imaging techniques, which provides additional evidence for the presumed cause of the stroke.Inhibitors of platelet function and anticoagulants are the two major groups of antithrombotic drugs used for the secondary prevention of stroke. Antiplatelet agents are still indicated in the majority of patients after ischaemic stroke, especially if an arterial origin is presumed. In addition to aspirin (acetylsalicylic acid), the position of which as the first-line antiplatelet drug is increasingly being questioned, other compounds with antiplatelet activity have been developed and have proven effective in secondary stroke prevention, including ticlopidine, clopidogrel and dipyridamole. Anticoagulants are principally indicated after cardioembolic ischaemic stroke; however, their inherent bleeding risks render their use in many cases rather difficult, in particular for elderly patients. Patient compliance with the recommended treatment is of major importance, given the somewhat limited efficacy of antithrombotic agents in stroke prevention. Since ‘real world’ experience does not match the circumstances under which clinical trials are conducted, this article will also deal with problems not covered by specific studies, such as risk stratification for anticoagulant treatment and how to proceed in cases of unknown stroke aetiology.The management of major cardiovascular risk factors is the other mainstay of secondary stroke prevention. Recent evidence indicates that antihypertensive treatment may be as effective as antithrombotic drugs for secondary prevention of stroke. This still needs to be proven for the treatment of other cardiovascular risk factors, such as diabetes mellitus and hypercholesterolemia. Nevertheless, the results of recent studies investigating the effect of HMG-CoA reductase inhibitors (‘statins’) on cardiovascular events strongly suggest a stroke-preventive effect.

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Methylphenidate is commonly used for the treatment of attention-deficit hyperactivity disorder (ADHD). Its efficacy in improving the core symptoms of ADHD, as well as some of the aggressive and oppositional behaviours, is well documented, based on a large volume of research. Methylphenidate has a wide margin of safety and relatively mild adverse effects, most commonly appetite suppression and insomnia.Methylphenidate is a rapidly absorbed medication that, in itsd-isomer form, readily penetrates the CNS, particularly the striatum. It appears to function by blocking the reuptake of dopamine.Both the plasma concentrations and behavioural effects of methylphenidate demonstrate a time to maximum of between 1 and 3 hours, with the maximum behavioural effects occurring when the plasma concentrations are increasing. Because of the rapid onset of action, the effects of methylphenidate can be dramatic but usually last only about 4 hours with the immediate-release formulation. The behavioural responses of individuals are also highly variable, so that it is necessary to start treatment at a low dosage and increase up to a maximally effective dosage (usually starting at 10–15 mg/day with increases of 10–15mg at weekly intervals to a maximum dosage of 60 mg/day, irrespective of formulation). Because of the variability in behavioural responses, assessment of plasma concentrations is not clinically useful nor does weight help in deciding an appropriate dosage. The difficulties in administering methylphenidate multiple times a day, particularly during the school day, have been alleviated in the past few years by the development of extended-release preparations with varying behavioural effects lasting 8–12 hours. The 8-hour preparations (Metadate®CD and Ritalin®LA) utilise a microbead technology, while the 12-hour preparation (Concerta®) utilises an osmotic pump system. All extended-release formulations effectively control the symptoms of ADHD. While pharmacokinetic differences appear to exist between some of these new formulations, there are currently no clinical data available to demonstrate clinical efficacy differences between them.

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

This review examines the development of dopamine partial agonists as a new class of antipsychotic agents. Partial agonists have a lower intrinsic activity at receptors than full agonists, allowing them to act either as a functional agonist or a functional antagonist, depending on the surrounding levels of naturally occurring neurotransmitter (full agonist). In the absence of a full agonist, partial agonists show functional agonist activity, binding to the receptor to produce a response. In the presence of a full agonist, partial agonists show functional antagonist activity, as receptor binding reduces the response from that seen with the full agonist. A partial agonist at dopamine D2receptors therefore offers an attractive option for the treatment of schizophrenia. It should act as a functional antagonist in the mesolimbic dopamine pathway, where excessive dopamine activity is thought to cause positive symptoms, but show functional agonist activity in the mesocortical pathway, where reduced dopamine activity is thought to be associated with negative symptoms and cognitive impairment. In addition, it should avoid the complete blockade of the nigrostriatal or tuberoinfundibular pathways, associated with extrapyramidal symptoms (EPS) and elevated prolactin levels, respectively.Clinical trials with aripiprazole – a new antipsychotic, which shows partial agonist activity at D2receptors and serotonin 5-HT1Areceptors, and antagonist activity 5-HT2Areceptors – have demonstrated the value of this treatment approach. Aripiprazole produced significant improvements in positive and negative symptoms in short- and long-term studies of patients with schizophrenia or schizoaffective disorder. Improvements occurred rapidly after the start of treatment, and were sustained throughout studies lasting up to 52 weeks. Significantly more patients responded to aripiprazole treatment than to haloperidol in the 52-week study, and aripiprazole-treated patients showed significantly greater improvements in negative and depressive symptoms than those receiving haloperidol. Aripiprazole treatment was well tolerated in both short- and long-term studies, showing a low liability for EPS and hyperprolactinemia, a lack of QTc prolongation, and minimal weight gain or sedation.In conclusion, the findings from clinical studies of aripiprazole show that dopamine partial agonists offer a novel, effective and well-tolerated treatment approach for patients with schizophrenia.

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS