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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Gallagher
Peter
P
Stanley Research Centre, School of Neurology, Neurobiology and Psychiatry, University of Newcastle upon Tyne, United Kingdom.
Watson
Stuart
S
Smith
Margaret S
MS
Ferrier
Ian Nicol
IN
Young
Allan H
AH
D000328:Adult; D000704:Analysis of Variance; D000928:Antidepressive Agents / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000627:therapeutic use; D018680:Cholinergic Antagonists / Q000627:therapeutic use; D003071:Cognition / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D006727:Hormone Antagonists / Q000627:therapeutic use*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008568:Memory / Q000187:drug effects*; D008875:Middle Aged; D015735:Mifepristone / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D011597:Psychomotor Performance / Q000187:drug effects; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D016896:Treatment Outcome
D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D018680:Cholinergic Antagonists; D006727:Hormone Antagonists; D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D006854:Hydrocortisone