Psychotic Depression—Beyond the Antidepressant/Antipsychotic Combination

Psychotic depression is an identified subtype of major depression that has many features of a distinct psychiatric disorder. Recent studies support previous findings that psychotic depression is associated with a less favorable course of illness. Moreover, the presence of a single psychotic symptom appears to predict decreased responsiveness to antidepressant monotherapy. Recent studies also support biological differences between psychotic and non-psychotic depression. Previous findings of greater HPA axis dysregulation are supported by evidence of diminished cortisol suppression with the mineralocorticoid antagonist fludrocortisone in psychotic depression. Moreover, a functional neuroimaging study demonstrated greater activation in parahippocampal and tempoparietal regions in psychotic depression during a memory task. In support of several previous treatment studies, a recent meta-analysis of studies that compared an antidepressant-antipsychotic combination to antidepressants or antipsychotics alone found a therapeutic advantage with the combined treatment over monotherapy. A recent clinical trial suggests that mifepristone, a glucocorticoid antagonist, may be an effective adjunctive treatment for psychotic depression.