Psychol Med. 2025 Oct 7;55:e294. doi: 10.1017/S0033291725101955.
ABSTRACT
BACKGROUND: With the increased prevalence of major depressive episodes with mixed features specifier (MDE-MFS), the pharmacological treatment for MDE-MFS has attracted great clinical attention. This study aimed to investigate the efficacy and safety of medication use for MDE-MFS.
METHODS: Commonly used databases were searched for the meta-analysis. Primary efficacy outcomes included response rate and the change in the Young Mania Rating Scale scores; the primary safety outcome was the rate of treatment-emergent hypomania/mania. Effects were expressed as relative risk (RR) or standardized mean difference (SMD).
RESULTS: In patients with MDE-MFS, antipsychotics significantly improved depressive (RR = 1.46 [95% CI: 1.31, 1.61]) and manic (SMD = -0.35 [95% CI: -0.53, -0.17]) symptoms without increasing the risk of manic switch (RR = 0.91 [95% CI: 0.53, 1.55]). However, subgroup analysis of bipolar disorder (BD) patients with MDE-MFS indicated that antipsychotics had limited effects on manic symptoms. Mood stabilizers, especially valproate, demonstrated significant effects in BD patients with MDE-MFS by relieving depressive and manic symptoms. For MDE-MFS in patients with major depressive disorder, trazodone has shown potential effectiveness in retrospective studies, while the effectiveness of antidepressants on BD patients with MDE-MFS lacked evidence.
CONCLUSIONS: While antipsychotics are first options for MDE-MFS, their effect on manic symptoms in BD patients with MDE-MFS is still unclear. Mood stabilizers may also be considered, and the use of antidepressants remains a topic of controversy. Since our findings are mostly based on post-hoc analyses, the evidence remains preliminary, highlighting the need for further research to produce more conclusive evidence.
PMID:41054794 | DOI:10.1017/S0033291725101955
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