摘要:

The most prevalent cause of dementia – Alzheimer’s disease – is characterised by an early cholinergic deficit that is in part responsible for the cognitive deficits, especially memory and attention defects, seen with this condition. Three cholinesterase inhibitors (ChEIs), namely donepezil, rivastigmine and galantamine, are widely used for the symptomatic treatment of patients with Alzheimer’s disease. Placebo-controlled, randomised clinical trials have shown significant effects of these drugs on global function, cognition, activities of daily living (ADL) and behavioural symptoms in patients with this disorder. These trials have been conducted for up to 12 months and were followed by open-label extension studies. One placebo-controlled, randomised clinical trial followed patients for up to 4 years. Both retrospective and prospective follow-up studies suggest a treatment effect for ChEIs that lasts for up to 5 years. Studies have shown comparable effects for ChEIs in patients with moderate-to-severe Alzheimer’s disease or mild Alzheimer’s disease. Clinically relevant responses consist not only of improvement over 3–6 months but also stabilisation and possibly slower than expected decline. Lack of overt clinical improvement in one domain (e.g. global function, cognition, ADL or behaviour) does not preclude clinically relevant benefit(s) in other domains.If it is judged that the patient has experienced a treatment effect from ChEI therapy during the first 6 months, it is recommended that treatment be continued for at least 1 year before discontinuation is considered again. On average, patients will return to their pre-treatment status between 9 and 12 months of initiation of treatment. However, this return to pre-treatment level does not mean that the treatment effect has disappeared. At this point in time, the patient may still function better than he or she would have without treatment. Setting a fixed measurement, e.g. a Mini-Mental State Examination score, as a ‘when to stop treatment limit’ is not clinically rational. The length of treatment should depend on several individual patient factors. The earlier the diagnosis is made and the slower the rate of disease progression, the longer the treatment period will tend to be. Treatment duration must therefore be evaluated on an individual basis, and the patient’s status compared with what would have been expected without treatment. If a clinical evaluation is conducted with a view to stopping or switching treatment, it is crucial that all domains are evaluated and that the patient is evaluated at more than one point in time before the decision is made.

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Pharmacological treatment of schizophrenia often requires careful dosage titration to achieve satisfactory symptom control whilst minimising the risk of adverse effects. Relapses requiring hospitalisation are an important potential source of additional cost for the health service and any inadequate symptom control increases the indirect costs of schizophrenia relating to, for example, the need for sheltered accommodation or intensive social services support.The availability of generic drugs is widely regarded as an opportunity to reduce expenditure on drug costs and deploy limited resources more widely and effectively. However, generic drugs may differ from branded drugs in their formulation and may not show precise bioequivalence with the branded product. This may have consequences for the pharmacokinetic profile of the generic drug. A higher maximum plasma concentration (Cmax) could lead to increased or emergent adverse effects, whereas a decreased absorption or minimum plasma concentration (Cmin) may result in a reduced therapeutic effect. For example, plasma levels of clozapine are critical to therapeutic response. Symptom aggravation occurred in approximately 10% of patients switched from branded to generic clozapine in a small, randomised, crossover study.Patients with schizophrenia may also show suspicion and hostility regarding their treatment. This may result in unwillingness to take an unfamiliar medication and decreased compliance, thus increasing the risk of a relapse.Thus, great care should be taken by psychiatrists when switching patients with schizophrenia from branded to generic antipsychotic drugs; this entails monitoring clinical outcome closely and adjusting the treatment in case of symptom aggravation or emergence of adverse effects.

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Multiple sclerosis (MS) is an inflammatory autoimmune disease characterised by demyelination and axonal loss in the CNS. Although new immunomodulatory therapies including interferon-β and glatiramer acetate became available during the last decade, these therapies are only partially effective. There is a continuing need to develop more effective treatment strategies to combat the chronic and progressive aspects of the disease. In view of the complex pathophysiology underlying the MS disease process, combination therapy offers a rational therapeutic approach. Combining immunomodulatory agents with different mechanisms of action that promote synergistic or additive effects represents an important objective in MS therapeutic research. Ultimately, the optimal therapies will likely include strategies that promote repair and limit tissue destruction in combination with anti-inflammatory interventions.

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Cervicogenic headache is a relatively common and still controversial form of headache arising from structures in the neck. The estimated prevalence of the disorder varies considerably, ranging from 0.7% to 13.8%. Cervicogenic headache is a ‘side-locked’ or unilateral fixed headache characterised by a non-throbbing pain that starts in the neck and spreads to the ipsilateral oculo-fronto-temporal area. In patients with this disorder, attacks or chronic fluctuating periods of neck/head pain may be provoked/worsened by sustained neck movements or stimulation of ipsilateral tender points. The pathophysiology of cervicogenic headache probably depends on the effects of various local pain-producing or eliciting factors, such as intervertebral dysfunction, cytokines and nitric oxide. Frequent coexistence of a history of head traumas suggests these also play an important role. A reliable diagnosis of cervicogenic headache can be made based on the criteria established in 1998 by the Cervicogenic Headache International Study Group. Positive response after an appropriate nerve block is an essential diagnostic feature of the disorder. Differential diagnoses of cervicogenic headache include hemicrania continua, chronic paroxysmal hemicrania, occipital neuralgia, migraine and tension headache.Various therapies have been used in the management of cervicogenic headache. These range from lowly invasive, drug-based therapies to highly invasive, surgical-based therapies. This review evaluates use of drug therapy with paracetamol and NSAIDs, infliximab and botulinum toxin type A; manual modalities and transcutaneous electrical nerve stimulation therapy; local injection of anaesthetic or corticosteroids; and invasive surgical therapies for the treatment of cervicogenic headache. A curative therapy for cervicogenic headache will not be developed until increased knowledge of the aetiology and pathophysiology of the condition becomes available. In the meantime, limited evidence suggests that therapy with repeated injections of botulinum toxin type A may be the most safe and efficacious approach. The surgical approach, which includes decompression and radiofrequency lesions of the involved nerve structures, may also provide physicians with further options for refractory cervicogenic headache patients. Unfortunately, the paucity of experimental models for cervicogenic headache and the relative lack of biomolecular markers for the condition mean much is still unclear about cervicogenic headache and the disorder remains inadequately treated.

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

In this article, we review the evidence that tocopherol (vitamin E) may have a role to play in the prevention and treatment of Alzheimer’s disease and other neurological diseases. The theoretical rationale for the effectiveness of tocopherol as treatment and/or prevention of Alzheimer’s disease is based on its antioxidant properties. Results from animal andin vitrostudies provide evidence to support use of tocopherol for prevention and treatment of degenerative neurological diseases. Furthermore, several, but not all, epidemiological, cross-sectional, prospective studies indicate that tocopherol may have protective effects in Alzheimer’s disease, although dietary and supplemental forms of the vitamin may differ in their efficacy. Mixed results have been obtained from clinical trials. Evidence of the use of tocopherol as a protective measure or as therapy in neurological diseases other than Alzheimer’s disease is less compelling. To date, there are no clear-cut answers as to whether tocopherol is worth prescribing, but current clinical practice favours its use in the treatment of Alzheimer’s disease.

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS