Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Mar 2012
FDA review divisions: performance levels and the impact on drug sponsors.
Sponsors of new drug applications (NDAs) confront a host of uncertainties, one of the more vexing of which is negotiating the differing and inconsistent policies and standards among the various US Food and Drug Administration (FDA) drug review divisions. The FDA faces many challenges as well, internal and external, that confound its efforts to provide a consistent and timely review process. In this article, we examine various input factors, such as the number of regulatory filings, that contribute to fluctuations in the annual FDA workload, as well as output factors, such as NDA approval times, that are often viewed by sponsors as measures of the FDA's performance. Interdivisional differences at the FDA, in both input and output factors as well as other process-related factors, such as issuance of complete response letters, division staff levels, and quality of the sponsor's application, are considered in light of their contribution to the vagaries of the sponsors' experiences with the regulatory process.
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Clin. Pharmacol. Ther. · Feb 2012
ReviewKetamine as a novel antidepressant: from synapse to behavior.
Recent reports of a rapid antidepressant effect of the glutamate N-methyl-D-aspartate (NMDA) receptor antagonist ketamine, even in treatment-resistant populations, have spurred translational therapeutic and neuroscience research aimed at elucidating ketamine's mechanism of action. This article provides a concise overview of research findings that pertain to the effects of low-dose ketamine at the cellular, neurocircuitry, and behavioral levels and describes an integrated model of the action of ketamine in the treatment of depression.
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Clin. Pharmacol. Ther. · Feb 2012
Plasma noradrenaline and state anxiety levels predict placebo response in learned immunosuppression.
Large interindividual differences exist in the presence and extent of placebo responses in both experimental and clinical studies, but little is known about possible predictors of these responses. We employed a behaviorally conditioned immunosuppression paradigm in healthy men to analyze predictors of learned placebo responses. During acquisition, the subjects received either the immunosuppressant cyclosporin A (n = 32) or a placebo (n = 14) (unconditioned stimuli (US)) together with a novel-tasting drink (conditioned stimulus (CS)). ⋯ Nonresponders (n = 17) did not show responses different from those of the controls. Multiple-regression analyses showed that baseline IL-2, plasma noradrenaline, and state anxiety predicted nearly 60% of the variance in the conditioned IL-2 response. These data provide first evidence for putative biological and psychological predictors of learned placebo responses.