A systematic review and meta-analysis of maintenance treatment for psychotic depression

Purpose: To perform a systematic review on the use of maintenance treatment to prevent relapse and recurrence in patients with psychotic unipolar or bipolar depression.

Methods: We conducted an electronic search in December 2019 (and an updated search in July 2021) of four databases (PubMed, Embase, PsycINFO, and Cochrane) to identify controlled studies comparing the relapse rates of patients receiving maintenance treatment for psychotic unipolar depression and psychotic bipolar depression. A meta-analysis was made that included three studies comparing antidepressant (AD) and antipsychotic (AP) combination therapy with AD monotherapy. We used the GRADE tool to assess the quality of evidence.

Results: We included five randomized controlled trials fulfilling the inclusion criteria, making three comparisons: (a) AD + AP versus AD monotherapy; (b) AD + AP versus AP monotherapy; (c) AD + electroconvulsive therapy versus AD monotherapy. The included studies only examined patients with psychotic unipolar depression. The largest included study reported a statistically significant advantage of AD + AP compared with AD monotherapy. We made a meta-analysis of the three studies comparing AD + AP combination therapy with AD monotherapy, which included 195 patients and 56 events. The meta-analysis did not show a statistically significant difference between these treatments.

Conclusions: Contrary to the finding of the largest study, we did not find a statistically significant difference between AD + AP combination therapy and AD monotherapy in the meta-analysis. There is insufficient evidence to support the superiority of any treatment modality as maintenance treatment for psychotic depression. Further studies are required.