Antiglucocorticoid treatments for mood disorders

Many patients with mood disorders report problems with memory and concentration, alongside their mood symptoms. There is some evidence that a possible cause of these problems is an overactivity of the hypothalamic-pituitary-adrenal (HPA) axis, the body's natural stress system. This leads to an overproduction of the stress-hormone, cortisol. Therefore, it is possible that drugs which target the HPA axis may be of benefit. The efficacy and safety of antiglucocorticoids in the treatment of mood disorders was the subject of this systematic review. Nine studies met criteria for inclusion. Of these, a number of drugs were examined, including: mifepristone [RU-486] (n=4), ketoconazole (n=2), metyrapone (n=2), and DHEA (n=1). Three of the trials were in patients with psychotic major depression (pMDD), five trials in non-psychotic major depression and one trial in patients with bipolar disorder (currently depressed; non-psychotic). Overall, when examining all trials together over all affective episodes, there was no significant difference in the overall proportion of patients responding (HAM-D 50% reduction) to treatment with antiglucocorticoids over placebo. However the mean change (WMD; baseline to end-point) in HAM-D scores indicated a significant difference in favour of treatment . There is clearer evidence of efficacy in specific diagnostic subtypes. Of the five trials in non-psychotic depression (unipolar or bipolar), there was a significant difference in favour of treatment. In psychotic depression, there was no evidence of an overall antidepressant effect or an effect on overall psychopathology (BPRS 30% reduction). In these subtypes the mean change (WMD) in scores indicated a significant difference in favour of treatment . To date only one trial has examined the impact of antiglucocorticoids on neuropsychological functioning. There are limited reports on side effects; overall, the only event to reach significance was the incidence of a rash occurring more often after active treatment, and this was reported in two studies . In summary, the use of antiglucocorticoids in the treatment of mood disorders and psychosis is very much at the proof-of-concept stage. A great deal of difference exists between studies with respect to the compounds used, patient cohort under investigation and methodology. Results in some diagnostic subtypes are promising and warrant further examination to better examine the clinical utility of this class of drug.