摘要:

There continues to be an escalation in the number of new antiepileptic drugs, with many recently marketed drugs and many more entering clinical trials. This growth begs the question as to whether we need additional antiepileptic drugs. We consider the answer to this question from the medical perspective and also from the viewpoint of the pharmaceutical industry, health providers and from a more global, international perspective.There is undoubtedly a medical need for new antiepileptic drugs, and despite growing competition, the antiepileptic drug market remains profitable. However, in health services with limited resources, it is important that this expense is not offset by failure to research more appropriate use of existing antiepileptic drugs that may have a greater impact on healthcare. This is especially true for developing countries where resources would be much better spent on prevention and closing the treatment gap (the difference between those who can be treated and those who are treated).

ISSN:1172-7047    

出版商:ADIS    

年代:2002

数据来源: ADIS

摘要:

Patients with epilepsy are at high risk for depression because of an incompletely understood combination of factors that may be both psychosocial and neurological. Interictal depression in patients with epilepsy is an undertreated condition, in part because of concern regarding drug interactions and the risk of exacerbating seizures with antidepressant treatment. Bipolar disorder is not described as occurring with a higher than expected frequency in the population with epilepsy, but high rates of depression and suicide are well recognised, highlighting the need for more emphasis on antidepressive treatment in this group of at-risk patients.Neurological factors, including site and lateralisation of seizure focus, may be important for the development of depression, with left-sided seizure foci having a higher association with depressive symptoms. Forced normalisation may be a factor in the paradoxical onset of depression in patients with epilepsy whose seizures suddenly become well controlled by anti-seizure treatment. Lowering of folic acid levels by some antiepileptic drugs (AEDs) may also influence the expression of depression in patients with epilepsy.New AEDs continue to emerge as beneficial treatments themselves for mood disorders, with lamotrigine, gabapentin and, to a lesser extent, topiramate having clinical trials data to support their use in patients with bipolar disease. Similar positive data are available for vagal nerve stimulation. Mood effects of AEDs can be complicated, however, as many of these drugs (e.g. tiagabine) have also been reported to cause depression as an adverse effect. Electroconvulsive therapy in depressed patients with epilepsy requires special consideration.The selective serotonin reuptake inhibitors (SSRIs) and antidepressants that act at multiple receptors (e.g. nefazodone, venlafaxine) are the most appropriate treatments for depressed patients with epilepsy. Among these agents, citalopram has a low risk of interactions with AEDs. Bupropion, clomipramine and maprotiline are associated with a greater risk of seizures compared with other antidepressants and consequently should be used with caution in the treatment of depression in patients with epilepsy.

ISSN:1172-7047    

出版商:ADIS    

年代:2002

数据来源: ADIS

摘要:

Cytomegalovirus (CMV) infection of the CNS occurs most commonly in patients with severe immunosuppression such as those with advanced HIV infection (i.e. AIDS) or those who have undergone bone marrow or solid organ transplantation. Immunocompetent patients are affected very rarely. The infection of the CNS may affect the brain (diffuse encephalitis, ventriculoencephalitis, cerebral mass lesions) or the spinal cord (transverse myelitis, polyradiculomyelitis). Diagnosis is very difficult and should be based on clinical presentation, results of imaging and virological markers. The most specific diagnostic tool is the detection of CMV DNA by polymerase chain reaction in the CSF. Treatment should be initiated promptly if CMV infection is suspected. Antiviral therapy consists of intravenous ganciclovir, intravenous foscarnet or a combination of both. Cidofovir is the treatment of second choice. Patients who experience clinical improvement or stabilisation during induction therapy should be given maintenance therapy. After immune reconstitution (in HIV-positive patients) or discontinuation of immunosuppressive therapy (in transplant recipients), maintenance therapy may be stopped. Despite therapy, the prognosis for long-term survival is very poor, especially in patients with AIDS.

ISSN:1172-7047    

出版商:ADIS    

年代:2002

数据来源: ADIS

摘要:

Clozapine is one of the most clinically potent drugs currently available for treating the symptoms of schizophrenia. Compared with conventional antipsychotics it surpasses its predecessors in its ability to treat a wider range of symptoms in otherwise refractory patients, while possessing a low propensity to produce extrapyramidal symptoms. Despite its significant advantages, not all patients benefit from treatment. Some patients react adversely to therapy while others fail to respond adequately. If those most likely to benefit from clozapine could be identified prior to treatment, this would significantly improve the clinical management of these patients.Genetic alterations in drug-metabolising enzymes have previously been demonstrated to influence the efficacy of clinically relevant drugs. It is possible that similar alterations in these and other systems may influence the response variability of patients to clozapine. Pharmacogenetic studies are at present investigating genes encoding drug receptors, drug-metabolising enzymes and neurotransmitter transporters to identify genetic variants that may be important. To date polymorphisms within serotonergic and dopaminergic pathways have been implicated, though the involvement of similar variants in other candidate systems is also likely. This information will ultimately enable the genetic prediction of patients most likely to benefit from the drug, and in the process would alleviate the unnecessary exposure of predisposed individuals to potentially serious adverse effects.

ISSN:1172-7047    

出版商:ADIS    

年代:2002

数据来源: ADIS

摘要:

In recent years, a broader base of treatment options has evolved to improve the outcome for patients with brain metastases. The selection of the most appropriate intervention for the individual patient is dependent on a careful evaluation of the extent of intracranial tumour, as well as an understanding of patient and tumour characteristics that are important determinants of prognosis. Recent analyses have confirmed good performance status, control of the primary tumour, absence of extracranial metastases and age less than 65 years to be predictors for longer survival.Medical therapy typically includes the use of corticosteroids, and some advances have been made in optimising the use of these agents. Prophylactic use of antiepileptic drugs in patients with brain metastases is generally discouraged.Chemotherapy was previously not considered to have a role in treating brain metastases, but has increasingly become an accepted treatment option. Recent clinical studies have evaluated the integration of chemotherapy with conventional treatments such as radiotherapy and the addition of biological response modifiers.In the past, radiotherapy has been the mainstay of treatment for brain metastases. A number of randomised controlled trials have explored external beam radiation therapy, radiation sensitisers, postoperative whole brain irradiation and prophylactic cranial irradiation. Significant improvements in survival have been demonstrated as a result of prophylactic cranial irradiation in patients with small-cell lung cancer, and improved local control of brain metastases has been achieved with postoperative whole brain irradiation. A number of studies have helped define a more efficient use of external beam irradiation. Radiosurgery in particular has been identified as an important advance in radiation treatment delivery and may provide an acceptable alternative to surgical resection in many patients.Conventional surgery has long had a role to play in establishing the diagnosis, guiding the choice of subsequent therapies and reversing life-threatening complications from brain metastases. The risks of surgery have been reduced with recent improvements in anaesthesia and intraoperative tumour localisation. Recent clinical studies have addressed the role of surgical resection in the management of patients with a single brain metastasis. Survival benefits have been demonstrated in patients undergoing surgical resection in addition to external beam radiation therapy.Despite the improvements achieved in the treatment of patients with brain metastases at first diagnosis, the question of retreatment may arise in due course. The therapeutic options available in this situation include re-operation, radiosurgery and brachytherapy.

ISSN:1172-7047    

出版商:ADIS    

年代:2002

数据来源: ADIS

摘要:

Abnormalities in the metabolism of the transition metals iron and copper have been demonstrated to play a crucial role in the pathogenesis of various neurodegenerative diseases. Metal homeostasis as it pertains to alterations in brain function in neurodegenerative diseases is reviewed in this article in depth. While there is documented evidence for alterations in the homeostasis, redox-activity and localisation of transition metals, it is also important to realise that alterations in specific copper- and iron-containing metalloenzymes appear to play a crucial role in the neurodegenerative process. These changes provide the opportunity to identify pathways where modification of the disease process can occur, potentially offering opportunities for clinical intervention. As understanding of disease aetiology evolves, so do the tools with which diseases are treated. In this article, we examine not only the possible mechanism of disease but also how pharmaceuticals may intervene, from direct and indirect antioxidant therapy to strategies involving gene therapy.

ISSN:1172-7047    

出版商:ADIS    

年代:2002

数据来源: ADIS

摘要:

BackgroundThe newer antidepressants are among the most commonly prescribed classes of medications. A favourable adverse effect profile and approvals for a wider range of disorders than their predecessors have fostered the growth of these drugs. However, newer antidepressants are appreciably more expensive than older medications, and the annual prescription costs of newer drugs are expected to continue to rise at double-digit rates. The price structuring of these medications is largely independent of their pill strengths, and splitting higher strength pills may reduce the average cost per dose by nearly half. Therefore, various health organisations and consumers have been using pill splitting to reduce prescription costs. Antidepressants are well suited for pill splitting because their therapeutic effects depend upon long-term alterations in neurotransmitters, and small variations in dose are not critical.ObjectiveTo examine the potential savings for various purchasers − health organisations and consumers − that can be derived from pill splitting of newer antidepressants.Design and settingProduct review and simulation study in the US healthcare setting.MethodsAll new antidepressants with pill strengths that could be halved and were not in capsular or time-release forms were included. Expenditures for purchasers of these pills were calculated using a variety of factors, such as the level of discounting of official average wholesale costs, average retail costs and the site of prescription dispensing.ResultsSeven antidepressants were included. In 2000, 42% of the pills of these antidepressants were at strengths that permitted splitting. If all eligible prescriptions had utilised split doses, purchasers could have saved over $US1.7 billion. The bulk of the saving ($US1.5 billion) would have been realised by pill splitting of only three medications − sertraline, paroxetine and citalopram.Discussion and conclusionsThe economic rationale for pill splitting of antidepressants is compelling for both health organisations and individual consumers. The literature indicates that when pill-splitters are used or a pharmacy cuts the pills, patients are satisfied and compliance is not reduced. However, pill splitting may be inadvisable for some subgroups of patients with reduced cognition or sensory or motor impairment, or older persons on polypharmacy. Pill splitting can be facilitated by mandating manufacturers to score all tablets, requiring pharmacists to fill prescriptions for split doses, and giving pharmacists incentives for splitting pills for patients. Finally, large-scale studies should be undertaken to examine the clinical effectiveness of, and financial savings from, pill splitting.

ISSN:1172-7047    

出版商:ADIS    

年代:2002

数据来源: ADIS

ISSN:1172-7047    

出版商:ADIS    

年代:2002

数据来源: ADIS