ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Multiple sclerosis (MS) is one of the most common chronic neurological diseases in young adults in western countries. An important aspect of treatment of this disease is the use of interferons (IFNs). These are molecules with antiviral, immunomodulatory, antiproliferative and hormonal activities. IFNβ, a class I IFN, has been used extensively in the therapy of MS, particularly in its relapsing-remitting (RRMS) phase, the most frequent clinical form of the disease.Although the available evidence from published clinical trials is difficult to evaluate because of methodological differences, an unbiased review of the data reveals sufficient evidence to conclude that treatment with IFNβ in RRMS is both efficacious and safe, at least over the periods so far investigated (up to 4–6 years). While there is no reason to suspect that IFNβ should not continue to be efficacious and safe over the longer term, studies investigating these questions over longer periods and including greater numbers of patients are needed.

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

At present, none of the neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s disease and stroke are treatable with compounds that slow or halt neuronal cell death. However, the prototype nitrone radical trap α-phenyl-tert-butylnitrone (PBN) has been shown to be an effective neuroprotective agent in various models of neurodegeneration. Some of these data are briefly reviewed as an introduction to an examination of the effect of the novel nitrone radical trapping agent disodium 2,4-disulfophenyl-N-tert-butylnitrone (NXY-059) in various animal models of stroke. NXY-059 has been shown to be an effective neuroprotective agent in both transient (reperfusion) and permanent focal ischaemia models in rats. In both types of model, NXY-059 has a large window of opportunity, providing effective neuroprotection when given up to 5 hours after the start of the occlusion in transient ischaemia and 4 hours after the start of permanent ischaemia. The compound is also effective in a marmoset permanent ischaemia model when administered up to 4 hours after the start of the occlusion. In this model it has been found to attenuate the problem of spatial neglect and maintain function to the paretic arm. NXY-059 administration also improves motor function in a rat haemorrhagic stroke model and has a neuroprotective effect in a rabbit thromboembolic stroke model. The compound is also well tolerated in stroke patients at plasma levels shown to provide a maximum neuroprotective effect in animal models of stroke.NXY-059, like PBN, is a nitrone with free radical trapping properties and this may be the basis of its neuroprotective action. However, experiments with PBN and NXY-059 suggest the possibility of other mechanisms being involved and these are also reviewed. Further experiments are required to fully elucidate the mechanism of action of these very effective neuroprotective agents.

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

The anilidopiperidine opioid remifentanil has pharmacodynamic properties similar to all opioids; however, its pharmacokinetic characteristics are unique. Favourable pharmacokinetic properties, minimally altered by extremes of age or renal or hepatic dysfunction, enable easy titration and rapid dissipation of clinical effect of this agent, even after prolonged infusion.Remifentanil is metabolised by esterases that are widespread throughout the plasma, red blood cells, and interstitial tissues, whereas other anilidopiperidine opioids (e.g. fentanyl, alfentanil and sufentanil) depend upon hepatic biotransformation and renal excretion for elimination. Consequently, remifentanil is cleared considerably more rapidly than other anilidopiperidine opioids. In addition, its pKa(the pH at which the drug is 50% ionised) is less than physiological pH; thus, remifentanil circulates primarily in the non-ionised moiety, which quickly penetrates the lipid blood-brain barrier and rapidly equilibrates across the plasma/effect site interface. By virtue of these distinctive pharmacokinetic properties, the context-sensitive half-time (i.e. the time required for the drug’s plasma concentration to decrease by 50% after cessation of an infusion) of remifentanil remains consistently short (3.2 minutes), even following an infusion of long duration (≥8 hours).Remifentanil, a clinically versatile opioid, is useful for intravenous analgesia and sedation in spontaneously breathing patients undergoing painful procedures. Profound analgesia may be achieved with minimal effect on cognitive function. Remifentanil may also provide sedation and analgesia during placement of regional anaesthetic blocks, and in conjunction with topical anaesthesia and airway nerve blocks, it may be useful for blunting reflex responses and facilitating ‘awake’ fibreoptic intubation.Compared with fentanyl and alfentanil in a day-surgery setting, remifentanil supplementation of general anaesthesia may improve intraoperative haemodynamic control. Both emergence time and the incidence of respiratory depression during post-anaesthetic recovery may be reduced. However, outcomes such as home discharge time, post-emergence adverse effect profile, and patient and provider satisfaction are not significantly improved, and the incidence of intraoperative hypotension and bradycardia is greater. In addition, drug acquisition costs for remifentanil are higher and clinicians may need extra time to familiarise themselves with the drug’s unique pharmacokinetics.Ironically, the quick dissipation of opioid analgesic effect following remifentanil discontinuation may be a significant clinical disadvantage. Unless little or no postoperative pain is anticipated, the clinician may wish to treat prospectively using local or regional anaesthesia, non-opioid analgesics, or longer-acting opioid analgesics.

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

Preclinical studies have contributed greatly to our understanding of the neurochemical pathways associated with the development and maintenance of alcohol-seeking behaviour. These studies have demonstrated the important role of serotonin pathways, particularly as they relate to dopaminergic function, which mediates alcohol-induced reward associated with its abuse liability. Naturally, this has led to the study of serotonergic agents as treatments for alcoholism.SSRIs do not appear to be effective treatment for a heterogeneous alcoholic group. However, they may be useful as treatment for late-onset alcoholics, or alcoholism complicated by comorbid major depression. Buspirone, a serotonin 5-HT1Apartial agonist, does not appear to be an effective treatment for alcoholics without comorbid disease. Buspirone may, however, have some utility for treating alcoholics with comorbid anxiety disorder. The 5-HT2antagonist ritanserin, at pharmacologically relevant clinical doses, does not appear to be an effective treatment for alcoholism. Ondansetron, a 5-HT3antagonist, is an efficacious and promising medication for the treatment of early-onset alcoholism. Preliminary evidence suggests that combining the mu antagonist naltrexone with the 5-HT3antagonist ondansetron promises to be more effective for treating alcoholism than either alone.The differential treatment effect of SSRIs and ondansetron among various subtypes of alcoholic is intriguing. Future research is needed to understand more clearly the molecular genetic differences and the interactions of such differences with the environment that typify a particular alcoholic subtype. Such an understanding could enable us to make comfortable predictions as to which alcoholic subtype might respond best to a particular serotonergic agent, which could then be provided.

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

ContextThe US FDA has issued an advisory warning of a possible link between antidepressant treatment for paediatric patients with major depressive disorder (MDD) and an increased risk of suicidal behaviour. A large database of paid health insurance claims for adolescents with MDD provided the opportunity to examine this possible relationship.ObjectiveTo examine the potential empirical link between antidepressant treatment and suicide attempts among adolescents aged 12–18 years using a community sample of managed care enrollees across the US.DesignA retrospective longitudinal cohort using paid insurance claims for all healthcare and prescription fills for adolescents who were newly diagnosed with MDD and had at least 6 months of follow-up data. A multivariate Cox proportional hazards regression analysis was used to test the hypothesis that antidepressant use increased the risk of suicide attempt, adjusting for propensity for allocation to each treatment group and for demographic and clinical characteristics.SettingManaged care plans including both commercial and Medicaid plans in the east, midwest, south and western regions of the US from January 1997 to March 2003.ParticipantsAll adolescent insurance members aged 12–18 years at first diagnosis of MDD.Main outcome measuresSuicide attempts as indicated by medical utilisation with International Classification of Diseases (9th edition) [ICD-9] or 10th edition (ICD-10) codes in any healthcare setting or by any covered provider.Results24 119 adolescents met inclusion criteria (63% female). Crude suicide attempt rates ranged from 0.0–2.3% by index treatment group. Treatment with SSRIs (hazard ratio) [HR] = 1.59; CI 0.89, 2.82), other antidepressants (HR = 1.03; CI 0.43, 2.44), or multiple antidepressants (HR = 1.43; CI 0.70, 2.89) after index MDD diagnosis resulted in no statistically increased risk of suicide attempt. Treatment with antidepressant medication for at least 180 days (6 months) reduced the likelihood of suicide attempt compared with antidepressant treatment for <55 days (8 weeks) [HR = 0.34; CI 0.21, 0.55]. Other variables that were independently associated with greater risk of suicide attempts included female gender, severity of illness indicators, younger age at time of MDD diagnosis, and living in the midwest or west.ConclusionsAntidepressant medication use had no statistically significant effect on the likelihood of suicide attempt in a large cohort of adolescents across the US after propensity adjustment for treatment allocation and controlling for other factors. The relationship between suicidal behaviour and antidepressant medication use is complex and requires further investigation.

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

ObjectiveTo determine the speed of onset of headache response and duration of response with zolmitriptan 5mg orally disintegrating tablet (ODT) in the acute treatment of migraine.BackgroundRapid pain relief is important for migraine sufferers. The early efficacy (30 minutes) of the 5mg dose of the zolmitriptan ODT formulation was evaluated.MethodsIn this double-blind, parallel-group trial, 670 patients were randomised to receive either zolmitriptan 5mg ODT (n = 329) or matching placebo (n = 341) to treat two migraine headaches of moderate or severe intensity.ResultsZolmitriptan 5mg ODT was significantly more effective than placebo in achieving a headache response (reduction in migraine headache intensity from moderate or severe to mild or no pain) at 30 minutes (16.5% vs 12.5%; p = 0.048; primary endpoint), 1 hour (p < 0.0001), and 2 hours (p < 0.0001). Significantly more patients achieved a sustained headache response for 24 hours with zolmitriptan 5mg ODT than with placebo (42.5% vs 16.4%; p < 0.0001). Zolmitriptan 5mg ODT also produced a higher pain-free rate than placebo at all timepoints (0.5, 1 and 2 hours post-dose), with the differences becoming significant at 1 hour. Adverse events were reported by 37.7% of the patients treated with zolmitriptan 5mg ODT and 18.1% of the patients treated with placebo. Those that occurred most often for the patients treated with zolmitriptan 5mg ODT were tightness (7.0%), dizziness (6.7%), somnolence (6.7%) and paraesthesias (6.1%).ConclusionsA significant headache response as early as 30 minutes post-dose and good maintenance of this headache response at 24 hours makes zolmitriptan 5mg ODT an excellent acute treatment for migraine. Together with the relatively low adverse event rate, these data demonstrate that zolmitriptan 5mg ODT is a valuable therapy for migraine sufferers.

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

IntroductionAlthough numerous studies have evaluated predictors of nursing home placement (NHP), few have focused on the effects of cholinesterase inhibitor (ChEI) use on NHP. The objective of this study was to compare the risk of NHP between rivastigmine patients versus no-ChEI patients (control group), and secondly, between rivastigmine versus donepezil patients.MethodsA retrospective analysis of a large US medical claims database was performed. Eligible subjects were identified from those who had continuous medical coverage from 1 April 2000 to 30 June 2002. Rivastigmine and donepezil subjects were new users, defined as having received no ChEI treatment during the initial 6 months of the study. Control subjects were diagnosed with Alzheimer’s disease (AD) at some point after the initial 6-month period. All subjects were followed from baseline (initiation of ChEI therapy or initial AD diagnosis) to the date of NHP or 30 June 2002, whichever occurred first.ResultsIn the rivastigmine (n = 1181), donepezil (n = 3864), and control (n = 517) groups, 3.7%, 4.4% and 11.0% of subjects, respectively, had an NHP (p < 0.001 for rivastigmine versus control). A Cox proportional hazard model, controlling for age, gender, comorbidities and behavioural disorders, showed that the control subjects were almost 3-fold more likely to have NHP than rivastigmine subjects (hazard ratio [HR] = 2.71; 95% CI 1.82, 4.03). The difference in the risk of NHP was not significant between the rivastigmine and donepezil groups (HR = 1.23; 95% CI 0.89, 1.71).DiscussionThis study demonstrated that rivastigmine decreased the risk of NHP in a large insured population.

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS

摘要:

IntroductionSeglor®capsules, a unique modified-release formulation of dihydroergotamine mesilate, have long been in clinical use in France for migraine prophylaxis. The aim of the PROMISE (PROphylaxis of MIgraine with SEglor®) study was to establish the efficacy and tolerability of Seglor®in the prevention of migraine in a general practice setting.MethodsThe PROMISE study was a double blind, placebo-controlled, parallel-group study carried out in primary care practice. It included 363 migraine patients treated with Seglor®or placebo for 5 months after a 1-month placebo run-in phase.ResultsMigraine attack frequency (primary efficacy criterion) decreased markedly in the two treatment groups so that the difference in favour of Seglor®did not reach statistical significance. However, most secondary outcome measures (duration of single attack, total duration of attacks over 1 month, consumption of mild opiate analgesics, subjective improvement) improved to a significantly greater degree in patients receiving Seglor®than in those receiving placebo. In the 84.5% of patients who had impaired quality of life at entry, the percentage of reduction in attack frequency and most other efficacy measures showed significant improvement with Seglor®. The safety profile for Seglor®was comparable to that of placebo.ConclusionThese results support the effectiveness of Seglor®in patients with migraine-related quality-of-life impairment. The findings of the PROMISE study also suggest that patients’ quality of life should be assessed systematically before initiating a preventive treatment for migraine.

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS

ISSN:1172-7047    

出版商:ADIS    

年代:2004

数据来源: ADIS