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Levodopa-induced dyskinesia can result in significant functional disability and reduced quality of life in patients with Parkinson's disease (PD). The goal of this study was to determine if the addition of once-daily ropinirole 24-hour prolonged-release (n = 104) in PD patients not optimally controlled with levodopa after up to 3 years of therapy with less than 600 mg/d delays the onset of dyskinesia compared with increasing doses of levodopa (n = 104). During the study, 3% of the ropinirole prolonged-release group (mean dose 10 mg/d) and 17% of the levodopa group (mean additional dose 284 mg/d) developed dyskinesia (P < 0.001). There were no significant differences in change in Unified Parkinson's Disease Rating Scale activities of daily living or motor scores, suggesting comparable efficacy between the two treatments. Adverse events were comparable in the two groups with nausea, dizziness, insomnia, back pain, arthralgia, somnolence, fatigue, and pain most commonly reported. Ropinirole prolonged-release delayed the onset of dyskinesia with comparable efficacy to increased doses of levodopa in early PD patients not optimally controlled with levodopa.

We performed a retrospective analysis of the Efficacy And Safety Evaluation in Parkinson's Disease (EASE-PD) Adjunct Study, assessing the minimum time to symptom improvement after initiation of ropinirole prolonged release (2-24 mg/day) versus placebo in patients with moderate-to-advanced PD not optimally controlled with levodopa. Ropinirole prolonged release was superior to placebo at Week 2 for change from baseline in "off" time (adjusted mean treatment difference [AMTD] - 0.7 hours; 95% confidence interval [CI], -1.1, -0.2; P = 0.0029), and "on" time without troublesome dyskinesia (0.4 hours; 95%CI, 0.01, 0.88; P = 0.0444). At Week 4, improvements were seen in change from baseline in Unified Parkinson's Disease Rating Scale total motor score (AMTD, -3.1; 95%CI, -4.4, -1.8; P < 0.0001), activities of daily living score (AMTD, -1.1; 95%CI, -1.7, -0.5; P = 0.0004), and the cardinal symptoms of PD compared with placebo. These analyses indicate that once-daily, adjunctive ropinirole prolonged release can offer PD symptom control 2 weeks after treatment initiation.

The tolerability of 311C90, a novel, selective and highly effective 5-HT1D receptor agonist in development for the acute treatment of migraine, has been evaluated in a number of clinical pharmacology and patient studies across the dose range 1-50 mg. 311C90 has been well tolerated across the entire dose range and no clinically relevant changes in routine laboratory parameters, blood pressure or ECG recordings have been observed. Adverse experiences reported are generally dose related, mild to moderate and resolve spontaneously. Chest-related symptoms occur infrequently and the cardiovascular safety profile of 311C90 is considered particularly favourable. 311C90, therefore, possesses a desirable safety profile which is well suited to broad-based outpatient administration.

In Alzheimer's disease, there is a marked decline in the function of cholinergic neurons in the brain. However, studies of treatment with cholinesterase inhibitors have produced conflicting results. We conducted a multicenter trial to evaluate whether the cholinesterase inhibitor tacrine (1,2,3,4-tetrahydro-9-acridinamine monohydrochloride monohydrate) could improve cognition in patients with Alzheimer's disease. Of 632 eligible patients with probable Alzheimer's disease, 215 improved while receiving tacrine during a preliminary crossover phase to determine responsiveness and the best dose. The 215 patients were randomly assigned to receive either placebo or their best dose of tacrine (10 or 20 mg four times a day) in a six-week, double-blind trial. The primary measures of efficacy were the cognitive subscale of the Alzheimer's Disease Assessment Scale and the Clinical Global Impression of Change scale; the secondary measures included the Mini-Mental State Examination and the assessment of the activities of daily living. At the end of the six-week trial, the patients receiving tacrine had a mean adjusted cognitive-subscale score of 30.3 (Alzheimer's Disease Assessment Scale) as compared with 32.7 in patients receiving placebo. This represents a smaller decline (by 2.4 points) in cognitive performance in the tacrine group (P