Psychotic depression differs significantly from non-psychotic depression in many aspects. These differences comprise etiology, severity, treatment response and prognosis.

The aim of the study was to assess the diversity of the psychiatric morbidity preceding psychotic and non-psychotic depression.

Danish, register-based, nationwide cohort study. Subjects were all Danish residents assigned with an ICD-10 diagnosis of severe depression with- (F32.3 and F33.3) or without (F32.2 and F33.2) psychotic symptoms between January 1^st 1994 and December 31^st 2007. Psychiatric diagnoses preceding the severe depression were assessed through the Danish Psychiatric Central Research Register. It was investigated whether patients with psychotic depression had a history of more diverse/severe psychiatric morbidity and a different use of psychopharmacological drugs prior to index, compared to their non-psychotic counterparts.

The study included 29,254 subjects with severe depression. Of these, 9,768 patients (33%) were of the psychotic subtype while 19,576 (67%) were non-psychotic.

Patients with the psychotic depressive subtype had a psychiatric history involving more and longer admission, more diverse diagnoses and a different pattern of psychopharmacological treatment compared to their non-psychotic counterparts. The results indicate, that psychotic depression may be more related to the bipolar/schizophrenia/psychosis spectrum than to the depression/anxiety spectrum.

The results add to a growing body of literature proving fundamental differences between psychotic- and non-psychotic severe depression. This should be considered in the upcoming revisions of the current diagnostic classifications.