Article

Clinical and biological effects of mifepristone treatment for psychotic depression.

Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305-5723, USA.
Neuropsychopharmacology (Impact Factor: 7.83). 04/2006; 31(3):628-36. DOI: 10.1038/sj.npp.1300884
Source: PubMed

ABSTRACT Psychotic major depression (PMD) is found to be a relatively common psychiatric condition that affects up to nearly 20% of patients with major depression. Previous studies by our group have shown rapid reversal of psychotic symptoms in some PMD patients treated with mifepristone, in addition to restoring a more normal afternoon cortisol release. The rationale for treating patients with PMD with a glucocorticosteroid receptor antagonist is further discussed. In total, 30 patients with PMD were treated with either 600 mg/day mifepristone or placebo for 8 days in a randomized double-blind manner. The Hamilton Depression Rating Scale (HDRS) and the Brief Psychiatric Rating Scale (BPRS) were administered at baseline and again after 8 days of treatment. Cortisol and ACTH were measured hourly from 1800 to 0900 at baseline and after 8 days of treatment. Significantly, more patients in the mifepristone group (seven of 15) showed a 50% or greater decline on the BPRS positive symptom subscale, an index of psychotic symptoms, as compared to the placebo group (two of 15). Patients who received mifepristone had lower HDRS and BPRS scores at study completion compared to those who received placebo, but these differences were not statistically significant. In addition, mifepristone significantly elevated cortisol and ACTH levels and steepened ascending slopes from 1800 to 0100 and from 0100 to 0900 as compared to placebo. Clinical and biological effects of mifepristone were comparable among males and females. Age was found to significantly and positively correlate with changes in cortisol and ACTH. These results suggest that short-term use of mifepristone may be effective in the treatment of PMD and may re-regulate the HPA axis. Additional blinded studies are warranted.

0 Bookmarks
 · 
112 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: When administered to normal healthy patients, a nonselective adenosine A1/A2A antagonist, caffeine, tended to improve anxiety and depression at low doses and to exacerbate anxiety at high doses. Caffeine also appears to enhance anxiety-related symptoms in patients with panic disorder, and A2A receptor-deficient mice have been reported to exhibit higher anxiety-like behaviors, as well as a lower incidence of depression-like behaviors. Some selective A2A antagonists were reported to ameliorate anxiety-like behaviors in rodents, while others did not affect these behaviors. In addition, most A2A antagonists showed inhibitory effects on depression-like behaviors. The mechanisms underlying the relationship between A2A receptor antagonists and anxiety and depression remain unclear at the present time, although many studies have produced hypotheses. Given that a selective A2A receptor antagonist has recently become available for use in humans, research on the role of A2A receptors in the treatment of mental illness should progress in the near future.
    International Review of Neurobiology 01/2014; 119C:373-393. · 2.46 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Regulating serotonin expression can be used to treat psychotic depression. Mifepristone, a glucocorticoid receptor antagonist, is an effective candidate for psychotic depression treatment. However, the underlying mechanism related to serotonin transporter expression is poorly understood. In this study, we cloned the human brain serotonin transporter into Xenopus oocytes, to establish an in vitro expression system. Two-electrode voltage clamp recordings were used to detect serotonin transporter activity. Our results show that mifepristone attenuates serotonin transporter activity by directly inhibiting the serotonin transporter, and suggests that the serotonin transporter is a pharmacological target of mifepristone for the treatment of psychotic depression.
    Neural Regeneration Research 03/2014; 9(6):646-52. · 0.23 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Both genetic and environmental factors play important roles in the pathophysiology of schizophrenia. Although prenatal hypoxia is a potential environmental factor implicated in schizophrenia, very little is known about the consequences of combining models of genetic risk factor with prenatal hypoxia. Heterozygous reeler (haploinsufficient for reelin; HRM) and wild-type (WT) mice were exposed to prenatal hypoxia (9% oxygen for two hour) or normoxia at embryonic day 17 (E17). Behavioral (Prepulse inhibition, Y-maze and Open field) and functional (regional volume in frontal cortex and hippocampus as well as hippocampal blood flow) tests were performed at 3 months of age. The levels of hypoxia and stress-related molecules such as hypoxia-inducible factor-1 α (HIF-1α), vascular endothelial factor (VEGF), VEGF receptor-2 (VEGFR2/Flk1) and glucocorticoid receptor (GR) were examined in frontal cortex and hippocampus at E18, 1 month and 3 months of age. In addition, serum VEGF and corticosterone levels were also examined. Prenatal hypoxia induced anxiety-like behavior in both HRM and WT mice. A significant reduction in hippocampal blood flow, but no change in brain regional volume was observed following prenatal hypoxia. Significant age and region-dependent changes in HIF-1α, VEGF, Flk1 and GR were found following prenatal hypoxia. Serum VEGF and corticosterone levels were found decreased following prenatal hypoxia. None of the above prenatal hypoxia-induced changes were either diminished or exacerbated due to reelin deficiency. These results argue against any gene-environment interaction between hypoxia and reelin deficiency.
    European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 06/2014; · 3.68 Impact Factor

Full-text (2 Sources)

Download
57 Downloads
Available from
May 27, 2014