Pharmacological treatment for psychotic depression

Background 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. This is an update of a review first published in 2005 and last updated in 2009. Objectives 1. To compare the clinical efficacy of pharmacological treatments for patients with an acute psychotic depression: antidepressant monotherapy, antipsychotic monotherapy and the combination of an antidepressant plus an antipsychotic, compared with each other and/or with placebo. 2. To assess whether differences in response to treatment in the current episode are related to non‐response to prior treatment. Search methods A search of the Cochrane Central Register of Controlled Trials and the Cochrane Depression, Anxiety and Neurosis Group Register (CCDANCTR) was carried out (to 12 April 2013). These registers include reports of randomised controlled trials from the following bibliographic databases: EMBASE (1970‐), MEDLINE (1950‐) and PsycINFO (1960‐). Reference lists of all studies and related reviews were screened and key authors contacted. Selection criteria All randomised controlled trials (RCTs) that included participants with acute major depression with psychotic features, as well as RCTs consisting of participants with acute major depression with or without psychotic features, that reported separately on the subgroup of participants with psychotic features. Data collection and analysis Two review authors independently extracted data and assessed risk of bias in the included studies, according to the criteria of the Cochrane Handbook for Systematic Reviews of Interventions. Data were entered into RevMan 5.1. We used intention‐to‐treat data. For dichotomous efficacy outcomes, the risk ratio (RR) with 95% confidence intervals (CIs) was calculated. For continuously distributed outcomes, it was not possible to extract data from the RCTs. Regarding the primary outcome of harm, only overall dropout rates were available for all studies. Main results The search identified 3659 s, but only 12 RCTs with a total of 929 participants could be included in the review. Because of clinical heterogeneity, few meta‐analyses were possible. The main outcome was reduction of severity (response) of depression, not of psychosis. We found no evidence for the efficacy of monotherapy with an antidepressant or an antipsychotic. However, evidence suggests