Biomedical subjects

Stuart Noble

Publications and source records attributed to Stuart Noble.

21 records · Page 2Linked to original sources

PubMed2002

Spotlight on sertraline in the management of major depressive disorder in elderly patients.

UNLABELLED: Sertraline is a selective serotonin reuptake inhibitor (SSRI) with well established antidepressant and anxiolytic activity. Results from several well designed trials show that sertraline (50-200 mg/day) is effective in the treatment of major depressive disorder in elderly patients (> or =60 years of age). Primary endpoints in most studies included the Hamilton Depression Rating Scale (HDRS), Clinical Global Impression score and the Montgomery-Asberg Depression Rating Scale. Sertraline was significantly more effective than placebo and was as effective as fluoxetine, nortriptyline and imipramine in elderly patients. During one trial, amitriptyline was significantly more effective than sertraline (mean reduction from baseline on one of six primary outcomes [HDRS]), although no quantitative data were provided. Subgroup analysis of data from a randomised, double-blind trial in elderly patients with major depressive disorder suggests that vascular morbidity, diabetes mellitus or arthritis does not affect the antidepressant effect of sertraline. Secondary endpoints from these clinical trials suggest that sertraline has significant benefits over nortriptyline in terms of quality of life. In addition, significant differences favouring sertraline in comparison with nortriptyline and fluoxetine have been recorded for a number of cognitive functioning parameters. Sertraline is generally well tolerated in elderly patients with major depressive disorder and lacks the marked anticholinergic effects that characterise the adverse event profiles of tricyclic antidepressants (TCAs). The most frequently reported adverse events in patients aged > or =60 years with major depressive disorder receiving sertraline 50-150 mg/day were dry mouth, headache, diarrhoea, nausea, insomnia, somnolence, constipation, dizziness, sweating and taste abnormalities. The tolerability profile of sertraline is generally similar in younger and elderly patients. Sertraline has a low potential for drug interactions at the level of the cytochrome P450 enzyme system. In addition, no dosage adjustments are warranted for elderly patients solely based on age. CONCLUSION: Sertraline is an effective and well tolerated antidepressant for the treatment of major depressive disorder in patients aged > or =60 years. Since elderly patients are particularly prone to the anticholinergic effects of TCAs as a class, SSRIs such as sertraline are likely to be a better choice for the treatment of major depressive disorder in this age group. In addition, sertraline may have advantages over the SSRIs paroxetine, fluoxetine and fluvoxamine in elderly patients because of the drug's comparatively low potential for drug interactions, which is of importance in patient groups such as the elderly who are likely to receive more than one drug regimen.

Aged↗

PubMed2002

Glatiramer acetate: a review of its use in relapsing-remitting multiple sclerosis.

UNLABELLED: Glatiramer acetate is a synthetic copolymer composed of a random mixture of four amino acids that modifies the immune response that results in the CNS inflammation, demyelination and axonal loss characteristic of relapsing-remitting multiple sclerosis (RRMS). In three randomised, double-blind trials in patients with RRMS, subcutaneous glatiramer acetate 20 mg/day was significantly more effective than placebo for the primary outcome measure of each trial (mean relapse rate, proportion of relapse-free patients and number of gadolinium-enhancing lesions on magnetic resonance imaging [MRI] scans). The mean relapse rate was significantly reduced at endpoint (approximately one-third less) in the two larger trials (the US pivotal trial [primary endpoint] and the European/Canadian study [tertiary endpoint]) in patients receiving glatiramer acetate compared with those receiving placebo. The rate was 78% less for glatiramer acetate than placebo patients in the pilot trial that investigated a slightly different patient population. Glatiramer acetate significantly decreased disease activity and burden of disease, as assessed in the European/Canadian study using a range of MRI measures. Patients with RRMS treated with glatiramer acetate in the US trial were significantly more likely to experience improved disability (whereas placebo recipients were more likely to experience worsening disability) and their overall disability status was significantly improved compared with placebo recipients. Data from the active-treatment extension of the US trial suggest that glatiramer acetate has sustained clinical benefits up to 8 years. Glatiramer acetate was generally well tolerated; the most commonly reported treatment-related adverse events were localised injection-site reactions and transient post-injection systemic reactions. Both reactions were generally mild and self limiting but were responsible for the majority of withdrawals from treatment (up to 6.5 and 3.5%, respectively). Glatiramer acetate is not associated with the influenza-like syndrome or neutralising antibodies that are reported in patients treated with interferon-beta for RRMS. The cost effectiveness of glatiramer acetate has yet to be definitively determined as assessment of available data is confounded by very different models, data sources and assumptions. CONCLUSION: Glatiramer acetate has shown efficacy in well controlled clinical trials in patients with RRMS; it reduces relapse rate and decreases MRI-assessed disease activity and burden. It is generally well tolerated and is not associated with the influenza-like symptoms and formation of neutralising antibodies seen with the interferons-beta. Based on available data and current management guidelines, glatiramer acetate is a valuable first-line treatment option for patients with RRMS.

Adjuvants, Immunologic↗

PubMed2002

Montelukast: a review of its therapeutic potential in asthma in children 2 to 14 years of age.

UNLABELLED: Montelukast is a cysteinyl leukotriene receptor antagonist which is used as a preventive treatment for persistent asthma in patients > or =2 years of age. In children aged 6 to 14 years montelukast (5 mg/day) treatment resulted in a significant increase in FEV(1) (forced expiratory volume in 1 second, primary clinical outcome) during an 8-week randomized, double-blind trial. Moreover, significant improvements were observed for a range of secondary endpoints assessing symptoms, exacerbation rates, beta-agonist usage and quality of life. Concomitant administration of montelukast (5 mg/day) and inhaled budesonide (200 microg twice daily) resulted in a trend towards an increase in FEV(1) (p = 0.06, primary endpoint) and a statistically significant reduction in both as-needed beta(2)-agonist usage and the percentage of days with asthma exacerbations compared with budesonide plus placebo. No significant differences were observed in asthma-related quality of life between the two groups. During clinical trials both improvements in lung function and reductions in as-needed beta(2)-agonist usage were generally observed within 1 day after initiation of therapy in children 2 to 14 years of age with persistent asthma. Data from a randomized, nonblind trial in 6- to 11-year-old children and a 6-month extension to this trial suggest that both compliance to therapy and patient satisfaction are greater for montelukast than for either inhaled sodium cromoglycate or inhaled beclomethasone. In addition, patients and parents preferred oral montelukast over sodium cromoglycate. In 2- to 5-year-old children with persistent asthma, montelukast (4 mg/day) treatment resulted in significant improvements in a range of outcomes, such as as-needed beta(2)-agonist usage, symptom scores and percentage of days with asthma symptoms, as assessed during a randomized, double-blind trial primarily designed to assess tolerability. Data from small randomized, double-blind trials suggest that montelukast reduces exercise-induced bronchoconstriction in 6- to 14-year-old children. Montelukast is generally well tolerated. The frequency of adverse events in montelukast-treated children of all ages was comparable to that in patients receiving placebo. CONCLUSION: Oral montelukast has shown efficacy as a preventive treatment for asthma during clinical trials in children aged 2 to 14 years. The drug offers benefits over more standard therapies such as inhaled sodium cromoglycate and nedocromil in terms of compliance and convenience. In addition, the drug offers significant benefits when added to inhaled corticosteroids (according to secondary endpoints). Montelukast offers an effective, well tolerated and convenient treatment option for children with asthma.

Acetates↗