摘要:

Epilepsy is a serious and common neurological disorder for which effective and well tolerated new agents continue to be sought. While the assessment of potential antiepileptic agents in animals models of epilepsy poses few problems, such assessment in humans is fraught with methodological and ethical dilemmas.Before the introduction of controlled clinical trials, agents that were though to have antiepileptic potential were merely administered to patients with epilepsy and the effects observed. Nowadays, many controls are placed on the testing of all new pharmacological agents, including antiepileptic drugs.The simplest method of assessing the efficacy of a new antiepileptic agent in humans is in a monotherapy, placebo-controlled trial. However, such a trial design poses serious ethical and moral issues due to the importance of achieving early optimal control of epileptic seizures in patients. Because of these difficulties, placebo-controlled monotherapy trials are rarely performed. Instead, add-on and crossover designs are used, each of which has its own inherent disadvantages. Thus, the ideal trial design which allows accurate and simple assessment of the efficacy of a new antiepileptic agent has still to be developed.

ISSN:1172-7047    

出版商:ADIS    

年代:1994

数据来源: ADIS

摘要:

A series of new and selective catechol-O-methyltransferase (COMT) inhibitors have been developed. Entacapone, nitecapone and tolcapone are nitrocatechol-type agents that are potent COMT inhibitorsin vitroand are activein vivoafter oral administration. CGP 28014 is a pyridine derivative that is active onlyin vivo.In animal studies, these compounds inhibit effectively theO-methylation of levodopa, thus improving its bioavailability and brain penetration, and potentiating its behavioural effects. Entacapone and nitecapone have mainly peripheral effects, whereas tolcapone and CGP 28014 inhibitO-methylation also in the brain. In human volunteers, entacapone, nitecapone and tolcapone inhibit dose-dependently COMT activity of erythrocytes. COMT inhibitors also decrease the levels of COMT-dependent metabolites of adrenaline (epinephrine) and noradrenaline (norepinephrine) in plasma.Entacapone, tolcapone and CGP 28014 improve the bioavailability of levodopa and inhibit the formation of 3-O-methyldopa in human volunteers. In initial clinical studies in patients with Parkinson's disease, both entacapone and tolcapone potentiated and prolonged the therapeutic effects of levodopa.

ISSN:1172-7047    

出版商:ADIS    

年代:1994

数据来源: ADIS

摘要:

The pharmacotherapy of epilepsy in children must account for a number of specific issues. The nature of epileptic disorders found in children differs from that in adults. For example, epilepsies of childhood are more likely to be developmentally or genetically based than those found in adults. Children also differ from adults in indications for antiepileptic drugs. Indeed, some types of childhood epilepsy do not require specific pharmacological treatment since prognosis is often excellent without therapy. This is especially true for children who are neurologically normal and those with benign epilepsy syndromes that have a characteristic electroclinical presentation, such as febrile seizures. In contrast, children with evidence of brain damage or those with serious epilepsy syndromes must be treated promptly.Once it has been decided that treatment is necessary, the choice of treatment should be based on a comparison of efficacy and tolerability of individual antiepileptic agents. The spectrum of toxicity is often different in younger patients from that in adults, and adverse effects that are acceptable in adults may be cause for discontinuation of therapy in children. Intellectual, cognitive and behavioural toxicity are particularly unacceptable.Establishing sustained therapeutic serum concentrations in children also requires specific attention. Rapid gastrointestinal transit times and interactions with milk and infant formulas may pose special management problems. Toxic metabolites of antiepileptic drugs are frequently produced in children. This can lead to drug hypersensitivity and other possible conditions, such as valproic acid (sodium valproate)-induced hepatotoxicity.Unless specific paediatric data are obtained, recommendations for the treatment of epilepsies in children will continue to be based on studies in adults and on anecdotal observations. Given the high prevalence and significant morbidity of childhood epilepsies, further studies of treatments are urgently needed.

ISSN:1172-7047    

出版商:ADIS    

年代:1994

数据来源: ADIS

摘要:

The skin is intricately involved with emotional and behavioural problems, both in a causative and a reactive way. This can lead to the development of psychodermatological disorders. In addition to its primary role of tactile receptivity, the skin reacts directly to emotional stimuli. The high visibility of dermatoses makes the skin a direct target for behavioural problems. Furthermore, self-destructive tendencies (such as dermatitis artefacta) and hypochondriacal features are often expressed through dermatological symptoms.In view of the clinical interface between dermatology and psychiatry, a combination of pharmacological and nonpharmacological (psychotherapeutic and behavioural) therapies is recommended for the treatment of psychodermatological disorders. Psychotropic drug treatments that may be useful include benzodiazepines, antidepressants and antipsychotics.

ISSN:1172-7047    

出版商:ADIS    

年代:1994

数据来源: ADIS

摘要:

During the last decade, much investigation into possible pharmacotherapy for eating disorders has been undertaken, especially for bulimia nervosa.Intensive hospital treatment compromising a combination of individual, group and family therapies with or without adjunctive pharmacological treatments are usually offered in anorexia nervosa. Osteoporosis and delayed gastric emptying are 2 medical complications that should be addressed as early as possible in the course of the disorder. Although not yet confirmed in controlled clinical trials, there is preliminary support for the use of hormone replacement therapy for anorexic patients with amenorrhoea. The short term use of prokinetic agents such as cisapride or domperidone may assist in the refeeding process.Despite several controlled clinical trials involving antipsychotic and antidepressant drugs, there is no pharmacological agent that has demonstrated superiority in enhancing the rate of bodyweight gain. Recently, uncontrolled and unblinded trials with fluoxetine in anorexia nervosa have offered promising results. However, further double-blind controlled evaluation is necessary to properly evaluate the role of fluoxetine or other selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs) in treating anorexia nervosa.In contrast to the limited literature on the treatment of anorexia nervosa, there have been a series of controlled clinical trials investigating treatments for bulimia nervosa. These have involving different forms of psychotherapy, both individual and group formats, or pharmacotherapy. Several investigators have also reported on the benefits of combining drug and psychological treatment in comparison to either approach on its own.SSRIs, monoamine oxidase inhibitors and tricyclic antidepressants have all been shown to offer symptomatic improvement in trials lasting between 6 and 24 weeks. A 24-week clinical trial of desipramine combined with individual cognitive therapy produced the best outcome.It is hoped that over time, with reduced cultural pressures to diet and with more emphasis on early detection of those individuals at risk of developing eating disorders, the occurrence and complications of these disorders will be reduced. Treatment research in the next decade will hopefully include clinical and biological predictors of response, meaningful long term outcome assessment, and novel interventions that will minimise the significant morbidity and mortality of these illnesses.

ISSN:1172-7047    

出版商:ADIS    

年代:1994

数据来源: ADIS

摘要:

Numerousin vitroandin vivoexperimental animal studies have demonstrated that gangliosides, particularly GM1 ganglioside (siagoside), may stimulate or accelerate the repair of peripheral and central nervous system neurons after various types of damage. Clinical studies of GM1 in peripheral neuropathies and stroke, disorders in which the effects of GM1 have been studied most extensively, have yielded inconsistent results. Problems of inadequate study design, inclusion of heterogenous clinical populations and variations in dosage, duration of treatment and timing of initial administration make it difficult to compare results from individual studies and to conclusively assess efficacy of GM1 treatment. Therefore, further clinical studies of gangliosides seem warranted.Despite efforts to link gangliosides with the development of Guillain-Barré syndrome, there are no valid data to support such an association. Gangliosides, in particular GM1, are well tolerated after repeated administration to humans and do not appear to be immunogenic.GM1 may be a useful therapeutic agent if administered to particular patients with a specific spectrum of symptoms and disease severity. In addition, to be effective the agents need to be administered in appropriate dosages and at an appropriate time after neuronal injury. Human clinical trials of gangliosides should continue cautiously and with restraint.

ISSN:1172-7047    

出版商:ADIS    

年代:1994

数据来源: ADIS

摘要:

Evidence is emerging that a range of psychotropic drugs may precipitate akathisia and/or panic reactions in predisposed patients. The use of fluoxetine has hitherto been the most notable example of this occurrence. These reactions may foster the genesis of suicidal ideation in a small proportion of patients. At present, it is not clear what biological mechanism may underlie this finding. The serotonin (5-hydroxytryptamine; 5-HT) system may be involved in these reactions.The best management of such reactions will involve counselling patients beforehand about the possibility of these reactions, stopping treatment with the agents if such a reaction is suspected, or adding an agent with 5-HT1Aantagonistic properties (e.g. propranolol) to the treatment regimen.

ISSN:1172-7047    

出版商:ADIS    

年代:1994

数据来源: ADIS

摘要:

Velnacrine is an hydroxylated derivative of the acetylcholinesterase inhibitor tacrine. The ability of velnacrine to increase cholinergic neurotransmissionin vitroprovides the rationale for its investigation as a potential treatment in patients with Alzheimer's disease, who are known to have reduced acetylcholine levels in the central nervous system. Single doses of velnacrine (100 or 150mg) attenuated cognitive impairment induced by central cholinergic blockade in healthy volunteers, and memory improved significantly in a small number of patients with Alzheimer's disease administered a 75mg dose.Evidence of efficacy for velnacrine is limited to results of briefly reported placebo-controlled studies. When administered in dosages of up to 225 mg/day for 6 weeks, velnacrine appeared to confer modest benefit in about one-third of 423 patients with Alzheimer's disease enrolled in a US dose-finding trial. Velnacrine 150 mg/day for 10 days was also considered superior to placebo in a small European trial involving 35 patients, notably in its effects on language, praxis and memory. Fuller results are anticipated from a 6-month investigation demonstrating efficacy for velnacrine 150 or 225 mg/day at 12-week interim analysis. Of interest is the finding from this trial that caregiver time assessed at 24 weeks was shorter for velnacrine compared with placebo recipients.The development of elevated plasma hepatic enzyme levels leading to treatment discontinuation in 27% of participants in the US trial, combined with the appearance of neutropenia in a few patients, has cast doubt over the tolerability profile of velnacrine. Ongoing investigations are endeavouring to identify the mechanism of the hepatotoxic effect, to establish whether a dose-response relationship exists, and to define possible subpopulations that may respond to velnacrine and those who may be at particular risk of developing hepatotoxicity. Other reported adverse events severe enough to cause treatment withdrawal have included rash, nausea, diarrhoea, headache and dizziness/fainting.In summary, questions surrounding the tolerability and efficacy of velnacrine must be resolved before its early promise as a treatment in Alzheimer's disease can be realised. Nonetheless, given the limited therapeutic options presently available, the drug may yet prove to be of value in at least some patients with Alzheimer's disease.

ISSN:1172-7047    

出版商:ADIS    

年代:1994

数据来源: ADIS