Arch Gen Psychiat
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Randomized Controlled Trial Clinical Trial
Development of a new once-a-day formulation of methylphenidate for the treatment of attention-deficit/hyperactivity disorder: proof-of-concept and proof-of-product studies.
The duration of action of the immediate-release formulation of methylphenidate hydrochloride is short (3 to 4 hours), and 3 times daily dosing is thought to maximize effectiveness across a 12-hour day. The initial sustained-release formulations of methylphenidate had reduced efficacy compared with immediate-release methylphenidate and were not well accepted. Tachyphylaxis was hypothesized to account for the reduced effects, and an ascending drug delivery pattern was proposed to overcome this acute tolerance. ⋯ These studies demonstrate the translation of a basic science finding (acute tolerance to clinical doses of methylphenidate) into clinical application (the selection of a new drug delivery pattern for methylphenidate). This approach produced a new product (OROS-methylphenidate or Concerta), which proved to have the predicted rapid onset (with 1-2 hours) and long duration of efficacy (10-12 hours) after a single administration in the morning.
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Serum anticholinergic activity (SAA), as measured by a radioreceptor assay, quantifies a person's overall anticholinergic burden caused by all drugs and their metabolites. In several small geriatric patient groups, SAA has been associated with cognitive impairment or frank delirium. To our knowledge, there has not yet been any systematic study of the prevalence of SAA and its effect on cognition in a community-based population. ⋯ To our knowledge, this is the largest analysis of SAA and the first to examine its extent and relationship with cognitive performance in a community sample. Its results suggest that SAA can be detected in most older persons in the community and confirm that even low SAA is associated with cognitive impairment.
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Comparative Study
Outpatient prescriptions for atypical antipsychotics for African Americans, Hispanics, and whites in the United States.
New antipsychotic medications introduced during the past decade-clozapine (1990), risperidone (1994), olanzapine (1996), and quetiapine fumarate (1997)-offer a decrease in serious adverse effects compared with traditional antipsychotic medications, but at up to 10 times the cost. We examined whether ethnic minorities achieve access to these new advanced treatments. ⋯ Early gaps between ethnic groups in receipt of atypical antipsychotic prescriptions decreased throughout the 1990s but persisted for African Americans with psychotic disorders.