A Preliminary Cross-Sectional Study of Bipolarity and Primary Pharmacotherapy in Long-Term Stable Patients with Major Depressive Disorder

Background Patients with major depressive disorder (MDD) who exhibit high bipolarity are at increased risk of future diagnostic conversion to bipolar disorder. However, treatment recommendations for MDD with bipolarity are constrained by limited direct evidence. We examined the association between bipolarity and primary pharmacotherapy in long-term stable outpatients with MDD and explored a clinically useful Bipolarity Index (BI) threshold. Methods In this two-center cross-sectional study, participants were classified into an antidepressant (AD) group or a mood stabilizer/second-generation antipsychotic (MS/SGA) group. Bipolarity was assessed with the BI. Receiver operating characteristic (ROC) analysis was used to identify a BI cutoff discriminating MS/SGA from AD. Results Of 106 participants, 57 were assigned to the AD group and 49 to the MS/SGA group. The BI score was significantly higher in the MS/SGA group than in the AD group (24.1 ± 12.9 vs 13.3 ± 6.9; p < 0.001). ROC analysis indicated a BI cutoff of 16 (Area Under the Curve = 0.768), yielding 69.4% sensitivity and 78.9% specificity for identifying the MS/SGA group. Conclusion Among long-term stable MDD outpatients, higher BI scores were associated with MS and/or SGA rather than antidepressant monotherapy as primary pharmacotherapy. A BI total score ≥ 16 may serve as a pragmatic threshold for identifying MDD patients with multiple bipolarity features who are more likely to receive MS and/or SGA. Prospective studies are warranted to test whether BI-guided pharmacotherapy improves outcomes and clarifies the role of MS and/or SGA in MDD patient with high bipolarity.