430 Combination therapy most effective for psychotic depression

July 06, 2014

PEARLS 430, May 2014, written by Brian R McAvoy

Clinical question
What is the most effective pharmacological treatment for psychotic depression?

Bottom line
The combination of an antidepressant plus an antipsychotic provided more effective treatment for psychotic depression than either treatment alone. The main outcome was reduction of severity of depression, not of psychosis. There was no evidence for the efficacy of monotherapy with an antidepressant or an antipsychotic. In all but one of the studies, no differences in overall dropout rates were reported between any of the treatment groups.

There were only 12 studies, and these included only small numbers of people. Few meta-analyses were possible because of clinical heterogeneity. There were differences between studies with regard to diagnosis, uncertainties around randomisation and allocation concealment, differences in treatment interventions (pharmacological differences between the various antidepressants and antipsychotics) and different outcome criteria.


In a European general population study, 18.5% of respondents with a major depressive episode had psychotic features; the prevalence of psychotic depression was 0.4% and of non-psychotic depression 2.0%.1 Compared with non-psychotic depression, psychotic depression is marked by greater severity, increased incapacity, a lower likelihood of placebo response, longer duration of episodes and recurrence of psychotic features in subsequent episodes. Evidence is limited regarding the most effective pharmacological treatment for psychotic depression: combination of an antidepressant plus an antipsychotic, monotherapy with an antidepressant or monotherapy with an antipsychotic.2

Cochrane Systematic Review

Wijkstra J et al. Pharmacological treatment for psychotic depression. Cochrane Reviews, 2013, Issue 11. Art. No.: CD004044.DOI: 10.1002/14651858. CD004044.pub3. This review contains 12 studies involving 929 participants.


1. Ohayon MM. Am J Psychiatry 2002;159:1855–61.
2. Coryell W. J Clin Psychiatry 1998;59:22–29.

Pearls are an independent product of the Cochrane primary care group and are meant for educational use and not to guide clinical care.