Cns Drugs
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Randomized Controlled Trial Multicenter Study Comparative Study Clinical Trial
Assessing therapeutic efficacy in a progressive disease: a study of donepezil in Alzheimer's disease.
To determine the value of continued donepezil treatment in patients with Alzheimer's disease for whom clinical benefit was initially judged to be uncertain. ⋯ Most patients showed clear clinical benefit during initial donepezil treatment. Among patients for whom clinical benefit was uncertain, improvement in cognition and behaviour were observed for those who continued donepezil treatment compared with the group switched to placebo. Initial decline or stabilisation does not necessarily indicate a lack of efficacy in Alzheimer's disease, and the decision to discontinue treatment should be based on an evaluation of all domains (cognition, behaviour and ADL) and performed at several timepoints.
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Subjective reports of sleep disturbance indicate that 70-91% of patients with post-traumatic stress disorder (PTSD) have difficulty falling or staying asleep. Nightmares are reported by 19-71% of patients, depending on the severity of their PTSD and their exposure to physical aggression. Objective measures of sleep disturbance are inconsistent, with some studies that used these measures indicating poor sleep and others finding no differences compared with non-PTSD controls. ⋯ Similarly, uncontrolled studies combining IRT and insomnia strategies have demonstrated good outcomes. Uncontrolled studies of continuous positive airway pressure for SDB in patients with PTSD show that this treatment led to significant decreases in nightmares, insomnia and PTSD symptoms. Controlled studies are needed to confirm these promising findings.
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Rivastigmine is a carbamate-type dual inhibitor of brain acetyl- and butyrylcholinesterases that has been evaluated in the symptomatic treatment of patients with mild to moderate dementia associated with idiopathic Parkinson's disease. Oral rivastigmine 3-12 mg/day for 24 weeks was significantly more effective than placebo in ameliorating cognitive and functional decline, including attentional deficits, in patients with Parkinson's disease dementia in a randomised, double-blind trial. ⋯ Rivastigmine appeared to be generally well tolerated, with the most common adverse events being mild to moderate in intensity and cholinergic in nature. Parkinsonian symptoms (mainly tremor) were more common in rivastigmine than placebo recipients.
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Parkinson's disease is a neurodegenerative disorder causing not only motor dysfunction but also cognitive, psychiatric, autonomic and sensory disturbances. Symptoms of dementia and psychosis are common: longitudinal studies suggest that up to 75% of patients with Parkinson's disease may eventually develop dementia, and the prevalence of hallucinations ranges from 16-17% in population-based surveys to 30-40% in hospital-based series. These cognitive and behavioural features are important in terms of prognosis, nursing home placement and mortality. ⋯ Certain atypical antipsychotics allow hallucinations, delusions and behavioural problems to be brought under control with minimal deleterious effects on motor function and cognition, but their safety in elderly patients has recently been called into question. Deep brain stimulation does not appear to be a useful treatment for cognitive and psychiatric dysfunction in patients with Parkinson's disease. Modafinil improves alertness in Parkinson's disease and warrants further investigation to establish its effects on cognitive performance.
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This review describes the medical, research and recreational uses of ketamine, an anaesthetic derivative of phencyclidine that has dissociative, analgesic and psychedelic properties. Ketamine has a complex mechanism of action that is further complicated by stereoselectivity; however, antagonism of glutamate NDMA receptors is thought to underlie its analgesic, dissociative and neuroprotective effects. While ketamine use in medical and veterinary settings is well documented and has a good safety record, the increase in its unregulated use outside of such controlled environments is a cause for concern. ⋯ The perceptual and mood changes observed in those who have consumed ketamine are highly sensitive to age, dose, route of administration, previous experience and setting. At low doses, stimulant effects predominate and the effect of environmental conditions are significant; with higher doses, psychedelic effects predominate and the effect of the environment diminishes. The potential of ketamine as a novel clinical and research tool is matched by its abuse potential outside medical settings.