Efficacy of Different Combination Therapies for Mania in Bipolar Disorder: A Systematic Review and Meta-Analysis

To systematically evaluate the efficacy and safety of different combination therapies in the treatment of mania in bipolar disorder, and to provide evidence-based support for individualized clinical treatment.

PubMed, Web of Science, Cochrane Library, CNKI, VIP, and Wanfang databases were systematically searched from inception to July 2025. Randomized controlled trials comparing ziprasidone or olanzapine combined with mood stabilizers (lithium carbonate or sodium valproate) for the treatment of manic episodes in bipolar disorder were included. Two reviewers independently performed literature screening, data extraction, and quality assessment. Meta-analysis was conducted using RevMan 5.4 software.

A total of 10 RCTs involving 842 patients were included. Meta-analysis showed no significant difference between the two groups in overall clinical efficacy (OR = 1.18, 95% CI: 0.80-1.75, p = 0.41). Ziprasidone was superior to olanzapine in reducing YMRS scores (MD = -1.47, 95% CI: -1.97-0.96, p < 0.00001). The incidence of adverse reactions was significantly lower in the ziprasidone group compared to the olanzapine group (OR = 0.16, 95% CI: 0.08-0.31, p < 0.00001). Furthermore, ziprasidone was associated with significantly greater increases in BDNF and T₃ levels after treatment.

Although the efficacy of ziprasidone plus mood stabilizers is comparable to that of olanzapine plus mood stabilizers in the treatment of manic episodes of bipolar disorder, ziprasidone offers advantages in improving manic symptoms (YMRS scores), reducing adverse events, and enhancing neuroendocrine indicators. It may serve as a favorable alternative in clinical practice. Further high-quality, multicenter, large-sample studies are needed to confirm its efficacy and safety.