摘要:

The results of recent clinical studies have challenged our previously held view that estrogen therapy promotes neurological health and prevents or ameliorates Alzheimer’s disease. A major question emerging from these studies is: how can there be such disparity between the basic science and epidemiological data that show that estrogen can protect neurons against degenerative insults and reduce the risk of Alzheimer’s disease and the recent data (from the Women’s Health Initiative Memory Study [WHIMS] trial and the trial of estrogen treatment for Alzheimer’s disease), which show that hormone replacement therapy (HRT) showed no benefit and even a potential deleterious effect? Which set of data is correct? The proposition put forth in this review is that both sets of data are correct and that two major factors determine the efficacy of estrogen or HRT.First is the time at which estrogen therapy is initiated. The data indicate that initiation of therapy early in menopause and when neurons are in a healthy state, reduces the risk of Alzheimer’s disease; whereas, estrogen therapy initiated after the disease has developed or decades following menopause is without benefit. Second, estrogen therapy is not the same as HRT and the type of progestogen used determines the outcome of the therapeutic intervention. Insights into the mechanisms of action of estrogen and progestogen in the brain provide a framework for understanding the paradox of the benefit of estrogen in the prevention of Alzheimer’s disease versus the lack of benefit in treatment trials and in trials when HRT is instituted many years after menopause.Based on estrogen-inducible mechanisms, which have been elucidated in healthy neuron model systems, it would be predicted that estrogen therapy could be highly effective in preventing neurodegenerative disease by promoting neuronal defence and memory mechanisms. The mechanisms of action of estrogen also predict that estrogen therapy would be an ineffective strategy for reversing the pathology of Alzheimer’s disease.In summary, the time at which estrogen therapy is initiated, the neurological status of the brain at the time of estrogen therapy initiation and the type of progestogen used all contribute to the efficacy of estrogen in preventing neurodegenerative disease and to sustaining neurological health and function. An estrogen advantage hypothesis is put forth that provides a unifying mechanism of estrogen action with implications for both the benefits and risks of estrogen therapy.

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

The association of alcohol dependence with suicidal behaviour is well established although complex. On the basis of epidemiological and clinical evidence, alcohol dependence is known to increase the risk for suicidal ideation, suicide attempts and completed suicide. However, this risk is modulated by a wide variety of factors including sociodemographic, clinical, treatment-related and life situational characteristics as well as current drinking status and the effect of inebriation. Treatment and management of patients with alcohol dependence and concomitant suicidal communication or suicide attempts is crucial, as is the recognition of these patients in emergency and other healthcare service contacts. The treatment strategies cannot be based on evidence derived from randomised clinical trials as such data do not exist. They must rather be based on current knowledge of risk factors for suicidal behaviour, efficacy of treatment for alcohol dependence or relevant co-morbid conditions and problems known to be common in treatment settings. In this article, we review the essential literature on the epidemiological and clinical research in the areas of alcohol dependence and suicidal behaviour.On the basis of current data and clinical experience, we suggest the following principles be followed in the management of alcohol-dependent individuals:suicidal threats or communication by alcohol-dependent individuals in emergency and other contacts should be taken seriously;other mental disorders should be well evaluated, a consequent treatment plan initiated and follow-up arranged;appropriate and up-to-date pharmacological treatment should focus on both reducing the amount of drinking and treating symptoms of other mental disorders;psychotherapeutic efforts should be focused on emerging symptoms of both alcohol use and other mental disorders; andknown epidemiological and clinical risk factors, adverse life events in particular, should be recognised and taken into account.

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Psychogenic movement disorders (PMDs) are best defined as hyper- or hypo-kinetic movement disorders, often associated with gait disorders, that cannot be directly attributed to a lesion or dysfunction of the nervous system and which are derived in most cases from psychological or psychiatric causes. There are a variety of PMDs including tremor, dystonia, parkinsonism, gait disorders and, even, unusual forms including paroxysmal dyskinesias. As has been recognised in the recent literature, PMDs cannot be strictly classified into clearly defined psychiatric disorders such as somatoform, dissociative or conversion disorders.In this review, we discuss the diagnosis of various PMDs (including hyper- and hypo-kinetic disorders; and current evidence for underlying comorbid disorders) and the current therapeutic approach to them. The therapy of PMDs is not well established, is very challenging to the clinician, and a better outcome can be achieved in the setting of a team approach involving movement disorders specialists, psychiatrists and therapists who specialise in cognitive-behavioural techniques. Current pharmacological and non-pharmacological approaches to treatment focus on therapy of underlying comorbid psychiatric and psychological issues, although compliance is a major concern.

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

This review focuses on current information about luteal phase administration (i.e. typically for the last 2 weeks of the menstrual cycle) of pharmacological agents for the treatment of premenstrual dysphoric disorder (PMDD). Compared with continuous administration, a luteal phase administration regimen reduces the exposure to medication and lowers the costs of treatment.Based on evidence from randomised clinical trials, SSRIs are the first-line treatment for PMDD at this time. Of these agents, sertraline, fluoxetine and paroxetine (as an extended-release formulation) are approved by the US FDA for luteal phase, as well as continuous, administration. Clinical trials of these agents and citalopram have demonstrated that symptom reduction is similar with both administration regimens. When used to treat PMDD, SSRI doses are consistent with those used for major depressive disorder. The medications are well tolerated; discontinuation symptoms with this intermittent administration regimen have not been reported.Other medications that have been examined in clinical trials for PMDD or severe premenstrual syndrome (PMS) using luteal phase administration include buspirone, alprazolam, tryptophan and progesterone. Buspirone and alprazolam show only modest efficacy in PMS (in some but not all studies), but there may be a lower incidence of sexual adverse effects with these medications than with SSRIs. Symptom reduction with tryptophan was significantly greater than with placebo, but the availability of this medication is strictly limited because of safety concerns. Progesterone has consistently failed to show efficacy for severe PMS/PMDD in large, randomised, placebo-controlled trials.

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Escitalopram (Cipralex®), a new highly selective inhibitor of serotonin reuptake, is the activeS-enantiomer ofRS-citalopram. It is effective in the treatment of patients with major depressive disorder (MDD) and may have a faster onset of therapeutic effect than citalopram. It has also been shown to lead to improvements in measures of quality of life (QOL). Escitalopram is generally well tolerated, with nausea being the most common adverse event associated with its use.Modelled pharmacoeconomic analyses found escitalopram to have a cost-effectiveness and cost-utility advantage over other SSRIs, including generic citalopram and fluoxetine and branded sertraline, and also over the serotonin-noradrenaline reuptake inhibitor (SNRI) venlafaxine extended-release (XR). These studies used a decision-analytic approach with a 6-month time horizon and were performed in Western Europe (year of  costing  2000  or  2001). Cost-effectiveness ratios for escitalopram, in terms of cost per successfully treated patient over 6 months, ranged from euro871 to euro2598 in different countries, based on direct costs and remission rates, and were consistently lower (i.e. more favourable) than the ratios for comparators (euro970–euro3472). Outcomes similarly favoured escitalopram when indirect costs (represented by those associated with sick leave and loss of productivity) were included. The results of comparisons with citalopram, fluoxetine and sertraline were not markedly affected by changes to assumptions in sensitivity analyses, although comparisons with venlafaxine XR were sensitive to changes in the remission rate.The mean number of quality-adjusted life years gained during the 6-month period was similar for all drugs evaluated, but direct costs were lower with escitalopram, leading to lower cost-utility ratios than for comparators. Incremental analyses performed in two of the studies confirmed the cost-effectiveness and cost-utility advantage of escitalopram.A prospective, 8-week comparative pharmacoeconomic analysis found that escitalopram achieved similar efficacy to venlafaxine XR, but was associated with 40% lower direct costs (euro85 vs euro142 per patient over 8 weeks; 2001 costs), although this difference did not reach statistical significance.In both the modelled and prospective analyses, the differences in overall direct costs were mainly due to lower secondary care costs (in particular those related to hospitalisation) with escitalopram. In the prospective analysis, escitalopram had lower estimated drug acquisition costs than venlafaxine XR.ConclusionEscitalopram, theS-enantiomer ofRS-citalopram and a highly selective inhibitor of serotonin reuptake, is an effective antidepressant in patients with MDD, has a favourable tolerability profile, and, on the basis of available data, appears to have a rapid onset of therapeutic effect. Modelled pharmacoeconomic analyses from Western Europe suggest that it may be a cost-effective alternative to generic citalopram, generic fluoxetine and sertraline. Although the available data are less conclusive in comparison with venlafaxine XR, escitalopram is at least as cost effective as the SNRI based on a prospective study, and potentially more cost effective based on modelled analyses. Overall, clinical and pharmacoeconomic data support the use of escitalopram as first-line therapy in patients with MDD.

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS