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: 7.05). 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.

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Available from: Heather A Kenna, Sep 28, 2015
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    • "He also showed evidence that administration of the glucocorticoid receptor antagonist, mifepristone, normalized DNA methylation in the dopamine projection, BDNF methylation and behavior deficits. Similarly, in a human trial, mifepristone has been shown to be effective in the treatment of psychotic depression by possibly re-regulation of the HPA axis (Flores et al., 2006). He further suggested that a subpopulation of patients or those at high risk for schizophrenia with an elevation in HPA axis expression could be targeted for treatment with mifepristone. "
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    Schizophrenia Research 10/2014; DOI:10.1016/j.schres.2014.08.032 · 3.92 Impact Factor
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    • "Based on the increased plasma corticosterone levels in the PrP-DN-DISC1 × social stress model, Niwa et al. treated the mice with the glucocorticoid receptor antagonist RU38486 which normalized all behavioral and dopaminergic cellular abnormalities in the G × E group, most likely via normalization of the tyrosine hydroxylase methylation. RU38486 is uniquely beneficial in psychotic depression, major depression with psychotic features (Flores et al., 2006), suggesting that the PrP-DN-DISC1 × social isolation model may be useful in finding better treatments for this disorder. The above drug treatment trials add predictive validity to their respective animal models and suggest that even abnormalities of neurodevelopmental origin may be reversed with appropriate treatment. "
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    • "Normalizing GR signaling early in the transition to dependence may block the sensitization of the brain stress systems, and the normalization of GR function after alcohol detoxification may reset the reward system to result in a shift from negative reinforcement to " normal " positive reinforcement or block the well documented sensitization of reward associated with protracted abstinence. Importantly, altered GR levels have been found in the superior frontal cortex of alcoholics (Liu et al., 2007; Ponomarev et al., 2012), and mifepristone has some promise for treating dysregulated mood (Flores et al., 2006; Nihalani and Schwartz, 2007; Blasey et al., 2009). "
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