Effects of adjunctive mifepristone (RU-486) administration on neurocognitive function and symptoms in schizophrenia

It has been suggested that hypercortisolemia may cause or exacerbate both neurocognitive impairment and symptoms in schizophrenia. We hypothesized that antiglucocorticoid treatments, particularly glucocorticoid receptor (GR) antagonists, would improve neurocognitive functioning and clinical symptoms in this disorder.

Twenty patients with schizophrenia were treated with 600 mg/day of the GR-antagonist mifepristone (RU-486) or placebo for 1 week in a double-blind, crossover design. Neurocognitive function was evaluated at baseline and 2 weeks after each treatment. Neuroendocrine profiling was performed at these times and also immediately after each treatment. Symptoms were evaluated weekly.

Mifepristone administration resulted in a temporary two- to threefold increase in plasma cortisol levels (p < .0001). No significant effects were observed on any measure of neurocognitive function, including the primary outcome measures of spatial working memory and declarative memory. Minor changes in symptoms occurred in both arms of the study and were indicative of a general improvement over time, irrespective of treatment.

In contrast to our earlier report of positive effects in bipolar disorder, these data suggest that the GR-antagonist mifepristone has no effect on neurocognitive function or symptoms in this group of patients with schizophrenia. Future studies in schizophrenia should examine patients with demonstrable hypothalmic-pituitary-adrenal axis dysfunction.