Pharmacological treatment of psychotic depression

Psychotic depression is challenging to treat. Electroconvulsive therapy has long been recognised as an effective treatment, 1 Buchan H Johnstone E McPherson K Palmer RL Crow TJ Brandon S Who benefits from electroconvulsive therapy? Combined results of the Leicester and Northwick Park trials. Br J Psychiatry. 1992; 160: 355-359 Crossref PubMed Scopus (88) Google Scholar but for several reasons, including patient choice, pharmacotherapy is frequently used instead. Two pairwise meta-analyses 2 Farahani A Correll CU Are antipsychotics or antidepressants needed for psychotic depression? A systematic review and meta-analysis of trials comparing antidepressant or antipsychotic monotherapy with combination treatment. J Clin Psychiatry. 2012; 73: 486-496 Crossref PubMed Scopus (98) Google Scholar , 3 Kruizinga J Liemburg E Burger H et al. Pharmacological treatment for psychotic depression. Cochrane Database Syst Rev. 2021; 12CD004044 PubMed Google Scholar have shown that the combination of an antidepressant plus an antipsychotic is more efficacious than either drug class alone in the acute treatment of psychotic depression. The rigorous network meta-analysis by Vincenzo Oliva and colleagues 4 Oliva V Possidente C De Prisco M et al. Pharmacological treatments for psychotic depression: a systematic review and network meta-analysis. Lancet Psychiatry. 2024; 11: 210-220 Google Scholar in this issue of The Lancet Psychiatry extends this line of enquiry by examining the efficacy and safety of specific drugs in the acute treatment of psychotic depression. 14 randomised controlled trials of various first-generation and second-generation antidepressants and antipsychotics were included in the network meta-analysis. Oliva and colleagues found that the combination of a selective serotonin reuptake inhibitor (SSRI) and a second-generation antipsychotic (SGA) was associated with the highest response rate (ie, the proportion of participants with an overall response to treatment) compared with placebo (risk ratio 1·89 [95% CI 1·17–3·04]). Fluoxetine plus olanzapine was the only specific treatment combination associated with a higher response rate than placebo (1·91 [1·27–2·85]). There was no difference in safety outcomes (defined as the proportion of participants who discontinued the study for any reason) between the combination of an SSRI and an SGA and placebo. 4 Oliva V Possidente C De Prisco M et al. Pharmacological treatments for psychotic depression: a systematic review and network meta-analysis. Lancet Psychiatry. 2024; 11: 210-220 Google Scholar Pharmacological treatments for psychotic depression: a systematic review and network meta-analysisAccording to the available evidence, the combination of a selective serotonin reuptake inhibitor and a second-generation antipsychotic—and particularly of fluoxetine and olanzapine—could be the optimal treatment choice for psychotic depression. These findings should be taken into account in the development of clinical practice guidelines. However, these conclusions should be interpreted cautiously in view of the low number of included studies and the limitations of these studies. Full-Text PDF