摘要:

Alzheimer’s disease is a dementing illness, the risk of which increases markedly with age. It is estimated that it consumes $US90 billion annually. Alzheimer’s disease is marked by an expanding cholinergic deficit, with a direct relationship between the degree of cholinergic dysfunction and the cognitive impairment. Substantial research continues to be focused on the development of newer and better medications, in particular acetylcholinesterase inhibitors (AChEIs), to compensate for the cholinergic deficit.Trial observations over the past several years suggest that in addition to positive effects on cognitive function, AChEIs may be able to decrease and ameliorate the neuropsychiatric symptoms frequently associated with Alzheimer’s disease. These observations have also shown that the instrumentation used can significantly influence the interpretation and outcome of a study. Typically the individual subscores of the noncognitive component of the Alzheimer’s Disease Assessment Scale (ADAS-noncog) and the Neuropsychiatric Inventory (NPI) scale have most consistently reflected the ability of AChEIs to improve the noncognitive behavioural problems and neuropsychiatric symptoms.Apathy and visual hallucinations are the symptoms that respond most positively to AChEIs. These agents may have the potential to decrease polypharmacy in this elderly population by achieving symptom reduction without additional use of antipsychotic medication.

ISSN:1172-7047    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

Pathological gambling is a prevalent disorder that is gaining attention from patients, clinicians and policy makers. Aetiological factors that have been related to pathological gambling include: (i) abnormalities in the serotonergic, dopaminergic and noradrenergic systems; (ii) cognitive distortions; and (iii) a reinforcement of the gambling activity by either episodic gains or the excitement that accompanies gambling. Male gender, urban residence, lower income and the presence of a comorbid psychiatric disorder (particularly substance abuse) appear to constitute risk factors for the presence of the disorder.A number of treatments have been suggested as potentially effective: Gamblers Anonymous, behavioural therapy, manualised cognitive therapy and several medications. At present, only manualised cognitive therapy and the selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor fluvoxamine have shown efficacy in systematic (albeit small) studies. However, much research remains to be done to better understand the psychophysiology of pathological gambling, to firmly demonstrate the efficacy of the different proposed treatment approaches, and to establish criteria for treatment selection for individual patients.

ISSN:1172-7047    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

This article reviews the evidence of the effects of atypical antipsychotics other than clozapine in patients with schizophrenia that is resistant to treatment with conventional agents. Clozapine remains the one drug with proven efficacy in patients with severely refractory symptoms. However, while the drug is modestly effective in 30 to 70% of these patients, there are many who are either intolerant of, or unresponsive to, it.The initial hope that the new atypical antipsychotics would play a major role in treatment-resistant schizophrenia has not really materialised. Nevertheless, it is increasingly recognised that perhaps the majority of patients with schizophrenia have milder degrees of refractoriness − so-called ‘partial responders’ − and considerable evidence is emerging for an important role for risperidone, olanzapine and quetiapine in these patients. These drugs appear to have advantages over the conventional antipsychotics in terms of both efficacy and tolerability in these patients.More studies are required to establish optimal dosages of the atypical antipsychotics in patients with refractory symptoms, as well as whether some individuals respond differentially to a particular drug.

ISSN:1172-7047    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

Benzodiazepines have been used as anxiolytics for many years, despite well described withdrawal effects and drug interactions. Serotonergic antidepressants, which benefit from a favourable adverse effect profile and do not cause dependence, are now established first-line treatments for anxiety disorders. It is apparent, however, that current treatments are not ideal, particularly as they do not always produce a complete recovery. Our growing knowledge of the neurobiology of anxiety disorders, aided by advances in neuroimaging and pharmacological challenges, has led to the development of other potential anxiolytics.Agents with increased specificity for serotonin receptor subtypes have been developed, with the aim of maximising therapeutic efficacy while minimising adverse effects. Novel anxiolytics, such as neuropeptide agonists and antagonists, γ-aminobutyric acid (GABA)Areceptor partial agonists, N-methyl-D-aspartate (NMDA) receptor antagonists, neurosteroids and others, are currently in development and may eventually offer alternatives to currently available agents.

ISSN:1172-7047    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

Atypical antipsychotics are characterised by a low propensity for causing acute and tardive extrapyramidal symptoms and an increased efficacy against positive and negative symptoms in schizophrenia. A growing literature suggests clozapine and other atypical antipsychotics, including olanzapine, risperidone, and possibly quetiapine and ziprasidone, are also effective in the treatment of bipolar disorder, particularly the manic phase. Symptoms that are refractory to other drugs may respond to these agents. However, antipsychotic treatment can be associated with serious adverse effects, and caution needs to be exercised in the prescription of these agents.

ISSN:1172-7047    

出版商:ADIS    

年代:2000

数据来源: ADIS

摘要:

Acetylcholinesterase (AChE) inhibitors are currently the most promising drugs available for the treatment of Alzheimer’s disease (AD). Their efficacy is based on the cholinergic hypothesis of AD which links reduced levels of cerebral acetylcholine (ACh) with declining cognitive function in affected individuals. AChE inhibitors are believed to work by increasing the level of ACh in the synaptic cleft by binding to local AChE and preventing the hydrolysis of ACh.Metrifonate differs from other AChE inhibitors in that it is a prodrug which is non-enzymatically convertedin vivoto the active moiety 2,2-dichlorovinyl dimethylphosphate (DDVP). DDVP administered alone has a very short plasma elimination half-life, but small amounts released from metrifonate are sufficient to inhibit AChE activityin vivo. DDVP is an irreversible inhibitor of AChE and activity is maintained for several weeks. Metrifonate has been used as an anthelmintic since 1962 and has been under investigation as a treatment for the symptoms of AD since 1990. Randomised, placebo-controlled clinical trials, using a variety of dose regimens, have demonstrated that metrifonate produces a significant, but modest, improvement in the 3 domains of AD: cognition, behaviour and function. However, it should be noted that with some assessment instruments in some trials, the ‘improvement’ was actually a reduction in the rate of worsening of symptoms compared with placebo. Weekly and daily schedules, with and without loading doses, have been evaluated and the research supports a fixed daily dose of 40 to 50mg, administered to supply approximately 0.65 mg/kg.In studies of up to 6 months’ duration, metrifonate was well tolerated, and adverse events were mild and predominantly gastrointestinal. In clinical practice it is likely that metrifonate will be administered for several years and long term monitoring of adverse events will be important to further define the drug’s tolerability profile. Muscle weakness occurred in a dose-related fashion in ≈20 of 3000 patients taking part in long term trials, and in some patients respiratory support was required. The mechanism of muscle weakness is not well defined and requires further investigation.ConclusionsClinical data support the use of metrifonate in patients with AD. However, the improvements noted are modest and to date there is no evidence that metrifonate is more effective than other currently approved AChE inhibitors. The unique pharmacokinetic/pharmacodynamic profile of metrifonate may endow the agent with some advantages over other therapies, but this has yet to be evaluated in comparative trials. Moreover, long term studies evaluating the effects of metrifonate on maintenance of independence are required. While the clinical future of metrifonate is uncertain, it is one of a small group of drugs that have been shown to improve the outlook of patients with AD.

ISSN:1172-7047    

出版商:ADIS    

年代:2000

数据来源: ADIS