A Randomized Trial to Examine the Effect of Mifepristone on Neuropsychological Performance and Mood in Patients with Bipolar Depression

• Published in: Biological psychiatry (1969) Vol. 72; no. 11; pp. 943 - 949
• Main Authors: Watson, Stuart, Gallagher, Peter, Porter, Richard J, Smith, Margaret S, Herron, Lisa J, Bulmer, Samantha, Young, Allan H, Ferrier, I. Nicol
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.12.2012; Elsevier
• Subjects: Adult; Adult and adolescent clinical studies; Affect - drug effects; Attention - drug effects; Biological and medical sciences; Bipolar disorder; Bipolar Disorder - drug therapy; Bipolar Disorder - physiopathology; Bipolar Disorder - psychology; Bipolar disorders; Double-Blind Method; Executive Function - drug effects; Female; glucocorticoid receptor; Hormone Antagonists - pharmacology; Hormone Antagonists - therapeutic use; Humans; Hypothalamo-Hypophyseal System - drug effects; Hypothalamo-Hypophyseal System - physiopathology; Male; Medical sciences; Memory, Short-Term - drug effects; Middle Aged; mifepristone; Mifepristone - pharmacology; Mifepristone - therapeutic use; Mood disorders; neuropsychological; Neuropsychological Tests; Pituitary-Adrenal System - drug effects; Pituitary-Adrenal System - physiopathology; progesterone; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; spatial working memory (SWM); Treatment Outcome; Verbal Learning - drug effects; Bipolar disorder; glucocorticoid receptor; mifepristone; spatial working memory (SWM); neuropsychological; progesterone; Mood disorder; Antineoplastic agent; Human; Affect affectivity; Neuropsychological test; Psychometrics; Cognition; Antihormone; Ovarian hormone; Progestagen; Mood; Abortifacient; Antiprogesterone; Glucocorticoid receptor; Mifepristone; Working memory; Progesterone; Sex steroid hormone; Spatial memory
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/j.biopsych.2012.05.029

Background Deficits in neuropsychological performance are found in patients with bipolar disorder and represent a potential treatment target for novel therapeutic strategies. We have previously demonstrated a beneficial effect on spatial working memory (SWM) of treatment for 1 week with the progesterone and glucocorticoid receptor antagonist mifepristone, evident 2 weeks after the cessation of treatment. Methods We examined the longer-term efficacy of 600 mg/day of mifepristone as an adjunctive treatment, for 1 week, in a placebo-controlled, randomized, double-blind trial in 60 patients with bipolar depression, with SWM as the primary outcome measure. A comparator group of healthy control subjects was also recruited. Results At baseline, neuropsychological performance of patients was impaired, but hypothalamic-pituitary-adrenal axis function did not differ from that of control subjects. Mifepristone treatment was associated with a time-limited increase in cortisol awakening response and with a sustained improvement in SWM performance, which was evident 7 weeks after the cessation of treatment. The magnitude of this neuropsychological response was predicted by the magnitude of the cortisol response to mifepristone. The response occurred in the absence of a significant improvement in depressed mood. Conclusions These data accord with the findings of animal studies and demonstrate that brief treatment with mifepristone is associated with a sustained improvement in SWM, an effect that might be mediated by a persistent enhancement in hippocampal mineralocorticoid receptor function.