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High circulating levels of glucocorticoid hormones adversely affect cognition. Previous studies exploring the hypothalamic-pituitary-adrenal (HPA) axis and basal cortisol levels in the elderly reported that subjects with mid-range cortisol levels outperformed subjects with high cortisol levels on assessments of memory and attention. This study examines the efficacy of mifepristone, a glucocorticoid-antagonist, in decelerating the rate of cortisol-related cognitive decline in subjects with mile-to-moderate Alzheimer's disease (AD). Rate of cognitve decline is compared in AD subjects randomized to receive 200 mg of mifepristone daily for 6 mo or placebo. The Alzheimer's Disease Assessment Scale (ADAS) and the Folstein Mini Mental Status Exam (MMSE) will be the primary measures used to assess change in cognitve function over the 6 mo period, supplemented by a neuropsychological battery testing memory and language and reasoning skills. During each visit, subjects will have samples collected for determination of plasma adrenocorticotropin (ACTH), serum cortisol and salivary cortisol levels to assess HPA axis activity. The placebo arm of this study also investigate whether subjects with high baseline cortisol levels experience greater declines in cognitive impairment over time relative to subjects with Ad who have low baseline cortisol levels. Additionally, this study test the hypothesis that AD subjects with elevated cortisol at baseline will perform more poorly on neuropsychological exams that do subjects with low cortisol.

The monaminergic properties of second generation antipsychotics are prompting research on their use to treat cocaine dependence, with inconclusive results to date. In preliminary reports, the atypical antipsychotic quetiapine has shown promise for the treatment of substance abuse disorders. The primary objective of the current study was to assess the efficacy of quetiapine in reducing cocaine cravings and use in nonpsychotic subjects with cocaine dependence over 6 weeks of open-label treatment. Twenty-two cocaine-dependent, nonpsychotic men were initiated to open-label treatment with quetiapine (300-600 mg/d). The primary outcome measure was weekly self-report of cocaine cravings as assessed with the Brief Substance Craving Scale. Cocaine use was captured with a self-report Timeline Follow-back calendar, administered every 2 weeks. Side effect monitoring was conducted weekly, and movement disorders were assessed every 2 weeks. Intent-to-treat regression analyses (n = 22) indicated that the Brief Substance Craving Scale total score decreased significantly overtime (P < 0.001). Self-reports also suggested decreased cocaine use. There was no treatment-related increase in movement disorders, and most side effects were mild. However, all subjects did experience sedation, and several subjects dropped out because of it. What is more, weight increased significantly over time (P < 0.001). Open-label quetiapine treatment reduced cravings and improved some aspects of cocaine dependence in nonpsychotic individuals. Additional research is needed to confirm the current findings and to further delineate the role quetiapine may play in the treatment of cocaine use disorders.

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