ABSTRACT
Fatigue and cognitive impairment are debilitating features of multiple sclerosis (MS). ENER-G was a 12-month, open-label, multicenter, single-arm observational study designed to evaluate changes in fatigue and cognition in MS patients treated with natalizumab. Adults with relapsing MS and initiating natalizumab were enrolled. The primary endpoint was change in Visual Analog Scale for Fatigue (VAS-F) score over 12 weeks. Changes in Modified Fatigue Impact Scale (MFIS) score, Fatigue Severity Scale (FSS) score, and cognitive performance, using Automated Neuropsychological Assessment Metrics (ANAM), were also assessed. Patients (N = 89) had a mean age of 41 years and a median Expanded Disability Status Scale score of 3.0, and 83% had used at least two prior MS therapies. Significant improvements were observed and maintained at 12 weeks in VAS-F (mean ± SD baseline score, 77.7 ± 10.2; mean ± SD change, -14.9 ± 17.1; P < .0001), MFIS (mean baseline score, 59.1 ± 12.2; mean change, -7.4 ± 11.8; P < .0001), and FSS (median baseline score, 6.3 [range, 3.9-7.0]; median change, -0.4 [range, -2.9-1.4]; P < .0001). Cognitive performance remained stable or improved (depending on the ANAM measure). Thus significant improvements in fatigue were maintained over time, and cognitive performance improved or remained stable up to 48 weeks after initiation of natalizumab in MS patients with some degree of fatigue.
ABSTRACT
Cognition has become increasingly important as an outcome measure in studies of medication. Traditional neuropsychological assessment is limited in its ability to detect subtle, medication-related changes and it is not suitable for the rapid serial assessment required in most clinical trials. Thus, investigators have turned to computerized neuropsychological assessment for its repeatability, sensitivity to subtle cognitive changes, and ease of administration. The automated neuropsychological assessment metrics (ANAM) is one such computerized battery that has been used to measure the effects of numerous CNS-active drugs. This paper is an exhaustive review of studies that have used ANAM to measure cognitive changes associated with pharmacological treatments. The benefits and limitations of using ANAM in clinical trials are discussed.
Subject(s)
Central Nervous System Agents/adverse effects , Cognition Disorders/chemically induced , Diagnosis, Computer-Assisted , Neuropsychological Tests , Software , Brain/drug effects , Central Nervous System Agents/therapeutic use , Central Nervous System Diseases/diagnosis , Central Nervous System Diseases/drug therapy , Central Nervous System Diseases/psychology , Cognition Disorders/diagnosis , Cognition Disorders/drug therapy , Cognition Disorders/psychology , Humans , Reference Values , Reproducibility of ResultsABSTRACT
Seasonal allergic rhinitis (SAR) and perennial allergic rhinitis (PAR) affect up to 40% of the population (depending on geographical area), and are associated with significant morbidity, socioeconomic costs and reductions in quality of life. Antihistamines are a first-line therapy, with newer nonsedating agents having superseded sedating first-generation drugs. Desloratadine is a nonsedating, nonimpairing antihistamine that is effective in relieving nasal and non-nasal symptoms of SAR and PAR, including nasal congestion. Desloratadine has a 24-h duration of action, enabling once-daily dosing and providing relief of morning symptoms. Clinical trials have demonstrated that it has no performance impairment, cardiovascular effects or clinically relevant interactions with other tested medications. This article reviews the use of desloratadine in the treatment of SAR and PAR.
ABSTRACT
BACKGROUND: Decrements in cognitive performance are associated with the use of sedating antihistamines. Most, but not all, second-generation antihistamines have been found to be nonsedating. OBJECTIVE: To examine the central nervous system (CNS) profile of a new second-generation antihistamine, desloratadine. METHODS: Subjects with ragweed-induced allergic rhinitis (aged 18-60 years) who demonstrated a predetermined severity of symptoms after priming with ragweed pollen in the Environmental Exposure Unit were randomized to receive a single dose of desloratadine, 5 mg; diphenhydramine, 50 mg; or placebo. A comprehensive battery of repeatable, automated neuropsychological tests was administered to subjects before treatment (symptomatic baseline) and 90 minutes after taking study medication. RESULTS: Both desloratadine (P = .04) and diphenhydramine (P < .01) alleviated the symptoms of allergic rhinitis compared with placebo, but treatment with diphenhydramine was associated with clinically meaningful decrements on all vigilance parameters (P < .05 for desloratadine-diphenhydramine contrasts). Also, subjects treated with diphenhydramine performed significantly worse than subjects given desloratadine or placebo across all cognitive domains evaluated. Most effect sizes for the mean desloratadine and diphenhydramine differences were between 0.4 and 0.8 (moderate to high). Stanford Sleepiness Scale scores also indicated significantly more somnolence with diphenhydramine vs desloratadine or placebo (P < .001). There were no significant differences on any of the cognitive parameters between subjects treated with desloratadine and those given placebo. CONCLUSIONS: Desloratadine improved ragweed-induced allergic rhinitis symptoms without adversely affecting performance. Diphenhydramine improved allergic rhinitis symptoms but caused significant decrements in vigilance and cognitive functioning. Thus, efficacy of antihistamine treatment must be balanced against the associated effects on CNS functioning.