Psychotic features, such as delusions of guilt or persecution, in major depressive disorder (MDD) attracted little research interest before the observation that patients with psychotic depression responded poorly to tricyclic antidepressants.1 Subsequent work showed that other depressive symptoms, particularly those of the melancholic subtype, are substantially more severe in this condition than they are in MDD without psychotic features.2 Second only to those with catatonic features, patients with psychotic features are most likely to experience hyperactivity of the hypothalamic-pituitary-adrenal axis3 and are much less likely than those without psychotic features to respond to placebo or to hospitalization alone.4
Coryell WH. Maintenance Treatment for Psychotic Depressive Disorders: Progress and Remaining Challenges. JAMA. 2019;322(7):615–617. doi:10.1001/jama.2019.9682
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