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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 abstracts, 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 that the combination of an antidepressant plus an antipsychotic is more effective than antidepressant monotherapy (three RCTs; RR 1.49, 95% CI 1.12 to 1.98, P = 0.006), more effective than antipsychotic monotherapy (four RCTs; RR 1.83, 95% CI 1.40 to 2.38, P = 0.00001) and more effective than placebo (two identical RCTs; RR 1.86, 95% CI 1.23 to 2.82, P = 0.003).Risk of bias is considerable: 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., Authors' Conclusions: Psychotic depression is heavily understudied, limiting confidence in the conclusions drawn. Some evidence indicates that combination therapy with an antidepressant plus an antipsychotic is more effective than either treatment alone or placebo. Evidence is limited for treatment with an antidepressant alone or with an antipsychotic alone.

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 abstracts, 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 that the combination of an antidepressant plus an antipsychotic is more effective than antidepressant monotherapy (three RCTs; RR 1.49, 95% CI 1.12 to 1.98, P = 0.006), more effective than antipsychotic monotherapy (four RCTs; RR 1.83, 95% CI 1.40 to 2.38, P = 0.00001) and more effective than placebo (two identical RCTs; RR 1.86, 95% CI 1.23 to 2.82, P = 0.003).Risk of bias is considerable: 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., Authors' Conclusions: Psychotic depression is heavily understudied, limiting confidence in the conclusions drawn. Some evidence indicates that combination therapy with an antidepressant plus an antipsychotic is more effective than either treatment alone or placebo. Evidence is limited for treatment with an antidepressant alone or with an antipsychotic alone.

Background: The optimal pharmacological treatment of unipolar psychotic depression is uncertain., Aims: To compare the clinical effectiveness of pharmacological treatments for patients with unipolar psychotic depression., Method: Systematic review and meta-analysis of randomised controlled trials., Results: Ten trials were included in the review. We found no evidence that the combination of an antidepressant with an antipsychotic is more effective than an antidepressant alone. This combination was statistically more effective than an antipsychotic alone., Conclusions: Antidepressant monotherapy and adding an antipsychotic if the patient does not respond, or starting with the combination of an antidepressant and an antipsychotic, both appear to be appropriate options for patients with unipolar psychotic depression. However, clinically the balance between risks and benefits may suggest the first option should be preferred for many patients. Starting with an antipsychotic alone appears to be inadequate.

Background: Regarding the pharmacological treatment of psychotic depression there is uncertainty about the effectiveness of an antidepressant alone compared to the combination of an antidepressant and an antipsychotic., Objectives: To compare the clinical effectiveness of pharmacological treatments for patients with a psychotic depression: antidepressant monotherapy, antipsychotic monotherapy, and the combination of an antidepressant and an antipsychotic, compared with each other and/or with placebo., Search Strategy: (1) The Cochrane Central Register of Controlled Trials (CENTRAL) was screened with the terms depressive disorder and drug treatment (April 2004). (2) MEDLINE (1966 to April 2004) and EMBASE (1980 to April 2004) were searched using terms with regard to treatment of unipolar psychotic depression.(3) Reference lists of related reviews and reference lists of all identified studies were searched.(4) Personal communications., Selection Criteria: All randomised controlled trials (RCTs) with patients with major depression with psychotic features as well as RCTs with patients with major depression with or without psychotic features which reported on the subgroup of patients with psychotic features separately., Data Collection and Analysis: Two reviewers assessed the methodological quality of the included studies, according to the Cochrane Handbook criteria. Data were entered into RevMan 4.2.5. We used intention-to-treat data. For dichotomous efficacy outcomes, the relative risk with 95% confidence intervals (CI) was calculated. For continuously distributed outcomes, it was not possible to extract data from the RCTs. Regarding the primary harm outcome, only overall drop-out rates were available for all studies., Main Results: The search identified 3333 abstracts, but only 10 RCTs with a total of 548 patients could be included in the review. Due to clinical heterogeneity, few meta-analyses were possible. We found no conclusive evidence that the combination of an antidepressant and an antipsychotic is more effective than an antidepressant alone (two RCTs; RR 1.44, 95% CI 0.86 to 2.41), but a combination is more effective than an antipsychotic alone (three RCTs; RR 1.92, 95% CI 1.32 to 2.80). There were no statistically significant differences in the overall drop-out rates between any of the treatments, neither in individual studies nor after pooling of studies., Authors' Conclusions: Treatment with an antipsychotic alone is not a good option. Starting with an antidepressant alone and adding an antipsychotic if the patient does not respond or starting with the combination of an antidepressant and an antipsychotic both appear appropriate options for patients with psychotic depression. In clinical practice the balance between risks and benefits suggests that initial antidepressive monotherapy and adding an antipsychotic if there is inadequate response should be the preferred treatment strategy for many patients. The general lack of available data limits confidence in the conclusions drawn.