title: A randomized trial to examine the effect of mifepristone on neuropsychological performance and mood in patients with bipolar depression.
abstract: 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.
authors: Academic Psychiatry, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors: Stuart
authors: S
authors: Watson
authors: Peter
authors: P
authors: Gallagher
authors: Richard J
authors: RJ
authors: Porter
authors: Margaret S
authors: MS
authors: Smith
authors: Lisa J
authors: LJ
authors: Herron
authors: Samantha
authors: S
authors: Bulmer
authors: Allan H
authors: AH
authors: Young
authors: I Nicol
authors: IN
authors: Ferrier
mesh_terms: D000328:Adult; D000339:Affect / Q000187:drug effects*; D001288:Attention / Q000187:drug effects; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D004311:Double-Blind Method; D056344:Executive Function / Q000187:drug effects; D005260:Female; D006727:Hormone Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects*; D008875:Middle Aged; D015735:Mifepristone / Q000494:pharmacology / Q000627:therapeutic use*; D009483:Neuropsychological Tests; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000503:physiopathology; D016896:Treatment Outcome; D014706:Verbal Learning / Q000187:drug effects
chemical_list: D006727:Hormone Antagonists; D015735:Mifepristone