摘要:

Post hocanalyses of pooled results from 11 randomised controlled trials of risperidone and olanzapine in elderly dementia subjects revealed an increased incidence of cerebrovascular adverse events compared with placebo. Reanalysis of the risperidone trials suggests that some of the increased incidence may be accounted for by nonspecific events that were not strokes. Large observational administrative health database studies appear to confirm that risperidone and olanzapine are not associated with an increased risk of stroke in elderly patients compared with typical antipsychotics or untreated dementia patients. A larger number of subjects with vascular and mixed dementias were included in the risperidone studies compared with the olanzapine studies, which likely accounts for the increased incidence of cerebrovascular adverse events in the risperidone trials compared with the olanzapine studies. Potential mechanisms proposed to explain an association between atypical antipsychotics and cerebrovascular adverse events include thromboembolic effects, cardiovascular effects (e.g. orthostatic hypotension, arrhythmias), excessive sedation resulting in dehydration and haemoconcentration, and hyperprolactinaemia. However, there is little evidence to support these hypothesised mechanisms at present. The association between atypical antipsychotics and cerebrovascular adverse events requires further clarification. At the present time, this association is another factor that clinicians should consider when weighing the risks and benefits of treating behavioural and psychological disturbances in elderly dementia patients.

ISSN:1172-7047    

出版商:ADIS    

年代:2005

数据来源: ADIS

摘要:

Recombinant preparations of the cytokine interferon (IFN)-α are increasingly used to treat a number of medical conditions, including chronic viral hepatitis and several malignancies. Although frequently effective, IFNα induces a variety of neuropsychiatric adverse effects, including an acute confusional state that develops rapidly after initiation of high-dose IFNα, a depressive syndrome that develops more slowly over weeks to months of treatment, and manic conditions most often characterised by extreme irritability and agitation, but also occasionally by euphoria. Acute IFNα-induced confusional states are typically characterised by disorientation, lethargy, somnolence, psychomotor retardation, difficulties with speaking and writing, parkinsonism and psychotic symptoms. Strategies for managing delirium should be employed, including treatment of contributing medical conditions, use of either typical or atypical antipsychotic agents and avoidance of medications likely to worsen mental status. Significant depressive symptoms occur in 21–58% of patients receiving IFNα, with symptoms typically manifesting over the first several months of treatment. The most replicated risk factor for developing depression is the presence of mood and anxiety symptoms prior to treatment. Other potential, but less frequently replicated, risk factors include a past history of major depression, being female and increasing IFNα dosage and treatment duration. The available data support two approaches to the pharmacological management of IFNα-induced depression: antidepressant pretreatment or symptomatic treatment once IFNα has been initiated. Pretreatment might be best reserved for patients already receiving antidepressants or for patients who endorse depression or anxiety symptoms of mild or greater severity prior to therapy. Several recent studies demonstrate that antidepressants effectively treat IFNα-induced depression once it has developed, allowing the vast majority of subjects to complete treatment successfully. Recent data suggest that IFNα-induced depression may be composed of two overlapping syndromes: a depression-specific syndrome characterised by mood, anxiety and cognitive complaints, and a neurovegetative syndrome characterised by fatigue, anorexia, pain and psychomotor slowing. Depression-specific symptoms are highly responsive to serotonergic antidepressants, whereas neurovegetative symptoms are significantly less responsive to these agents. These symptoms may be more effectively treated by agents that modulate catecholaminergic functioning, such as combined serotonin-noradrenaline (norepinephrine) antidepressants, bupropion, psychostimulants or modafinil. Additional factors to consider in selecting an antidepressant include potential drug-drug interactions and adverse effect profile. Finally, IFNα appears capable of inducing manic symptoms. Mania, especially when severe, is a clinical emergency. When this occurs, IFNα and antidepressants should be stopped, an emergency psychiatric consultation should be obtained, and treatment with a mood stabiliser should be initiated.

ISSN:1172-7047    

出版商:ADIS    

年代:2005

数据来源: ADIS

摘要:

IntroductionMigraine is a common, disabling condition that has a significant impact on patients and relatives, and is a considerable economic burden on society. Migraine patients want fast-acting treatments with high efficacy. Previous studies have demonstrated that orally administered formulations of zolmitriptan are rapidly and highly effective in the acute treatment of migraine. The objective of this study was to assess the efficacy, speed of onset and tolerability of the nasal spray formulation of zolmitriptan in migraine treatment.Zolmitriptan nasal spray was well tolerated, with most adverse events being of short duration and mild or moderate intensity.MethodsThis multicentre, randomised, double-blind study recruited 2122 patients (aged 18–65 years) who had an established diagnosis of migraine (according to International Headache Society criteria), with or without aura. Patients were randomised to receive zolmitriptan 5mg nasal spray or placebo to treat up to two migraine attacks within 15 minutes of headache pain becoming moderate or severe. The primary endpoint was headache response (reduction in migraine pain from severe/moderate to mild/none) at 2 hours, 1 hour, 30 minutes and 15 minutes post-dose (analysed using a step-down approach). Secondary endpoints included headache response at 4 hours, pain-free rates at 30 minutes and 1, 2 and 4 hours, and sustained headache response and pain-free status at 24 hours post-dose.Zolmitriptan nasal spray was well tolerated, with most adverse events being of short duration and mild or moderate intensity.ResultsThe headache response rate at 2 hours post-dose was 66.2% for the zolmitriptan group, compared with 35.0% for the placebo group (p < 0.001). Zolmitriptan nasal spray also produced significantly higher headache response rates than placebo at all earlier timepoints assessed, starting as early as 15 minutes post-dose (p < 0.001). Similar results were obtained for the analysis of the first attack. Significantly higher pain-free rates were obtained with zolmitriptan nasal spray, compared with placebo, from 15 minutes post-dose onward (p < 0.005). Zolmitriptan nasal spray was also significantly superior to placebo for headache response at 4 hours, sustained headache response at 24 hours and sustained pain-free rate at 24 hours.Zolmitriptan nasal spray was well tolerated, with most adverse events being of short duration and mild or moderate intensity.ConclusionsZolmitriptan nasal spray is highly effective in the acute treatment of migraine and has a very fast onset of action, producing significant headache response and pain-free rates as early as 15 minutes post-dose (the earliest assessment in this study). In addition to the very fast onset of action, zolmitriptan nasal spray produced significantly higher sustained headache response and pain-free rates at 24 hours post-dose compared with placebo. These desirable efficacy outcomes were combined with good tolerability.

ISSN:1172-7047    

出版商:ADIS    

年代:2005

数据来源: ADIS

摘要:

IntroductionDepression is a major global problem associated with large medical, sociological and economic burdens. Mirtazapine (Remeron®, Organon NV, The Netherlands) is an antidepressant with a unique mechanism of action that has similar or superior efficacy to TCAs and SSRIs in moderate-to-severe depression. However, this agent has not yet been tested in patients with severe depression alone.ObjectiveTo compare the antidepressant efficacy and tolerability of mirtazapine and fluoxetine and their effects on anxiety and quality of life in patients with severe depression (≥25 points on the first 17 items of the Hamilton Depression Rating Scale [HDRS-17]).MethodsIn this double-blind study, 297 severely depressed patients were randomised to receive mirtazapine 15–60 mg/day (n = 147) or fluoxetine 20–40 mg/day (n = 152) for 8 weeks. 294 subjects were actually treated and 292 included in the intent-to-treat population. Symptom severity was measured by the HDRS-17, Montgomery-Äsberg Depression Rating Scale (MADRS) and Clinical Global Impression (CGI) rating scale. Quality of life was self-assessed by patients using the Leeds Sleep Evaluation Questionnaire and the Quality of Life, Enjoyment and Satisfaction Questionnaire. Adverse events were recorded throughout the study.ResultsNo statistically significant differences were noted between the two groups in change from baseline HDRS-17 score at any time point; both treatments were associated with large (~15 points) decreases by study end. However, more mirtazapine-treated patients tended to exhibit a ≥50% decrease in HDRS score (significant at day 7; 9.0% vs 0.7%, p = 0.002). Significant differences in favour of mirtazapine were also observed at day 14 for changes in MADRS scores (−10.9 vs −8.5, p = 0.006) and the proportion of patients with ≥50% decrease in MADRS score (21.4% vs 10.9%, p = 0.031). On the CGI, the proportion of ‘much/very much improved’ patients tended to be greater with mirtazapine (significant at day 7; 9.7% vs 3.4%, p = 0.032). No significant between-group differences were observed for the majority of quality-of-life measures. However, mirtazapine produced significantly better improvements on ‘sleeping assessment 1’ (14.9 ± 5.2 vs 13.7 ± 5.4, p = 0.028) and ‘sleeping assessment 2’ (p = 0.013) than fluoxetine. Both agents were generally well tolerated but mirtazapine-treated patients experienced a mean weight gain of 0.8 ± 2.7kg compared with a mean decrease in weight of 0.4 ± 2.1kg for fluoxetine-treated patients (p < 0.001).ConclusionsMirtazapine is as effective and well tolerated as fluoxetine in the treatment of patients with severe depression.

ISSN:1172-7047    

出版商:ADIS    

年代:2005

数据来源: ADIS

摘要:

Intramuscular olanzapine (Zyprexa®) is a rapid-acting atypical antipsychotic drug that is also indicated for use in patients with agitation associated with schizophrenia or bipolar mania, the focus of this review. Evidence from three well designed trials indicates that this formulation of olanzapine is at least as effective as intramuscular haloperidol or lorazepam in the treatment of patients with acute agitation associated with schizophrenia or bipolar mania, and has a faster onset of action. Although transient reductions in blood pressure and heart rate may occur in some patients administered intramuscular olanzapine, preliminary evidence of a general lack of clinical effect on the corrected QT (QTc) interval and a low incidence of extrapyramidal symptoms (EPS) is promising. The parenteral formulation of olanzapine appears to offer an effective, fast-acting and generally well tolerated alternative in the treatment of this significant behavioural problem.

ISSN:1172-7047    

出版商:ADIS    

年代:2005

数据来源: ADIS

摘要:

Tolcapone (Tasmar®) is a selective, reversible inhibitor of peripheral and central catechol-O-methyltransferase (COMT).Results of well designed studies indicate that oral tolcapone is an effective adjunct to levodopa plus a peripheral dopa-decarboxylase inhibitor (DDCI) in patients with fluctuating Parkinson's disease. Tolcapone significantly improves levodopa-induced motor fluctuations and significantly reduces levodopa requirements. The drug is generally well tolerated, with the most commonly occurring adverse events being dopaminergic related. Thus, tolcapone is a useful option in patients with fluctuating Parkinson's disease who are receiving levodopa/DDCI and are not responding to, or are not candidates for, other adjunctive treatments.

ISSN:1172-7047    

出版商:ADIS    

年代:2005

数据来源: ADIS