Discovery of a novel non-steroidal GR antagonist with in vivo efficacy in the olanzapine-induced weight gain model in the rat.

We report the optimization of a series of non-steroidal GR antagonists that led to the identification of compound 7. This compound is efficacious when dosed orally in an olanzapine-induced weight gain model in rats.

Efficacy and safety of mifepristone for the treatment of psychotic depression.

Open-label studies and randomized clinical trials have suggested that mifepristone may be effective for the treatment of major depression with psychotic features (psychotic depression). A recent study reported a correlation between mifepristone plasma concentration and clinical response. The current study aimed to evaluate the safety and efficacy of mifepristone and, secondarily, to test whether response was significantly greater among patients with mifepristone plasma concentrations above an a priori hypothesized threshold.

Selective glucocorticoid receptor (type II) antagonists prevent weight gain caused by olanzapine in rats.

The use of antipsychotic medication has consistently been associated with serious side effects including weight gain and metabolic abnormalities. Strategies for mitigating these side effects have been tested, yet effective interventions have not been identified. The current study tested whether two recently identified selective glucocorticoid receptor antagonists would prevent weight gain induced by the antipsychotic olanzapine.

Mifepristone reduces weight gain and improves metabolic abnormalities associated with risperidone treatment in normal men.

Antipsychotic medications are associated with significant weight gain, type 2 diabetes mellitus, dyslipidemia, and increased cardiovascular risk. The objective of this study was to determine whether mifepristone, a glucocorticoid receptor antagonist, could prevent risperidone-induced weight gain. Using a 2:2:1 randomization scheme, 76 lean, healthy men (BMI 18-23 kg/m(2)) age 18-40 years were randomized to risperidone (n = 30), risperidone plus mifepristone (n = 30) or mifepristone (n = 16) daily for 28 days in an institutional setting.

Mifepristone treatment of olanzapine-induced weight gain in healthy men.

Introduction: Antipsychotic medications are associated with significant weight gain, type 2 diabetes mellitus, dyslipidemia, and increased cardiovascular risk. Suggested mechanisms of weight gain from antipsychotic medication include antagonism of histamine and serotonin receptors, and effects on the hypothalamic-pituitary-adrenal axis. The objective of this study was to determine if mifepristone, a glucocorticoid receptor antagonist, could prevent olanzapine-induced weight gain.

A multisite trial of mifepristone for the treatment of psychotic depression: a site-by-treatment interaction.

Major Depression with Psychotic Features (psychotic depression) is a common, debilitating psychiatric disease. We hypothesized that mifepristone, a cortisol receptor (GRII) antagonist, would significantly reduce psychotic symptoms in psychotic depression. Two hundred fifty-eight patients with psychotic depression enrolled at 29 sites were randomized to mifepristone or placebo for 7 days.

Beyond the three-component model of organizational commitment.

This article offers a conceptual critique of the three-component model (TCM) of organizational commitment (Allen & Meyer, 1990) and proposes a reconceptualization based on standard attitude theory. The authors use the attitude-behavior model by Eagly and Chaiken (1993) to demonstrate that the TCM combines fundamentally different attitudinal phenomena. They argue that general organizational commitment can best be understood as an attitude regarding the organization, while normative and continuance commitment are attitudes regarding specific forms of behavior (i.