title: Psychotic major depression: a benefit-risk assessment of treatment options.
abstract: Numerous studies in the past three decades have characterised 'psychotic major depression', a subtype of major depression which is accompanied by delusions or other psychotic features. Evidence from phenomenological and neurobiological investigations indicates that this is a unique disorder with clinical and biological characteristics that are distinct from those of nonpsychotic depression and from other psychotic disorders. Treatment studies have provided evidence of small placebo effects and good responses to electroconvulsive therapy or combination treatment with an antidepressant plus an antipsychotic agent. However, until recently, there were only a few small, prospective, double-blind, controlled trials investigating the efficacy of antidepressant-antipsychotic combination pharmacotherapy, yet this constitutes the currently accepted and most universally applied 'standard of care' for psychotic depression. Treatment guidelines have been based largely on uncontrolled investigations of electroconvulsive therapy and studies using tricyclic antidepressants and first-generation antipsychotic drugs, which are not frequently chosen as first-line agents today because of concerns regarding tolerability and risks. However, recent open-label studies and large controlled trials of newer antidepressants and antipsychotics have yielded very divergent results thus far, so that the best treatment approach remains elusive. This review discusses the phenomenology and treatment of psychotic depression with a focus on the benefits and risks of various treatment approaches. Problems with this literature are highlighted, and strategies for future research are suggested.
authors.affiliation: Mood Disorders Research Program, and the Department of Psychiatry and Human Behavior, Brown Medical School, Butler Hospital, Providence, Rhode Island 02906, USA. Audrey_Tyrka@Brown.edu
authors.forename: Audrey R
authors.initials: AR
authors.lastname: Tyrka
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Price
authors.forename: Marcelo F
authors.initials: MF
authors.lastname: Mello
authors.forename: Andrea F
authors.initials: AF
authors.lastname: Mello
authors.forename: Linda L
authors.initials: LL
authors.lastname: Carpenter
mesh_terms: D000928:Antidepressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use; D003362:Cost-Benefit Analysis; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000628:therapy*; D004359:Drug Therapy, Combination; D004565:Electroconvulsive Therapy; D006801:Humans; D006854:Hydrocortisone / Q000037:antagonists & inhibitors; D016032:Randomized Controlled Trials as Topic; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors; D018570:Risk Assessment
chemical_list: D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D011965:Receptors, Glucocorticoid; D006854:Hydrocortisone