Psychotic Depression: What Is It and How Should We Treat It?

Abstract

The National Institute of Mental Health’s recent call for a research proposal for investigating the effectiveness of the new atypical antipsychotics for psychotic depression has generated a lot of head-scratching among experts in mooddisorders research. Close reflection on the evolution of the diagnosis and our current American Psychiatric Association treatment guidelines for psychotic depression leads one to conclude that our field doesn’t quite have a handle on this disorder. Three decades of research has produced only two prospective, double-blind, controlled trials investigating the efficacy of antidepressant-antipsychotic combination pharmacotherapy using tricyclic antidepressants (TCAs) and conventional antipsychotic agents, 1,2 yet this combination constitutes the currently accepted standard of care for psychotic depression. In an era when both the pharmaceutical industry and government are providing fairly abundant support for research on all aspects of depression, how this important subtype could be neglected is hard to imagine. Why has it been so difficult to advance our understanding of the best treatment for psychotic depression? For one thing, the systematic study of “psychotic,” or “delusional,” depression has been limited by the fact that broadly accepted operational criteria for the disorder did not exist until 1980, when the third edition of the Diagnostic and Statistical Manual of Mental Disorders 3 was published. Previously, psychiatrists had considered delusions in the context of depressed mood to be a somewhat nonspecific phenomenon that occasionally occurred at the severe end of the depressive disorders spectrum 4 or, when more bizarre in content, concomitant with the “schizoaffective” form of schizophrenia.