All-Cause and Cause-Specific Mortality in Patients With Bipolar II Disorder

Importance: Whether bipolar II disorder (BD-II) is associated with increased long-term mortality remains uncertain because most studies have not distinguished BD-II from bipolar I disorder (BD-I). Objective: To examine whether BD-II is associated with elevated all-cause and cause-specific mortality compared with population controls, unaffected siblings, and those with BD-I. Design, Setting, and Participants: This population-based, retrospective cohort study used data from Taiwan's National Health Insurance Database from January 1, 2000, to December 31, 2022. Individuals 12 years or older with 2 or more psychiatrist-assigned BD-II diagnoses were individually matched to 4 controls without BD-II by sex and birthdate. Additional comparisons included unaffected biological siblings and a BD-I cohort. Follow-up was from the index date to death or December 31, 2022. Data were analyzed from June to August 2025. Exposures: Clinical diagnosis of BD-II. Main Outcomes and Measures: Primary outcome was all-cause mortality; secondary outcomes were natural-cause and unnatural-cause mortality. Cox proportional hazards regression models estimated adjusted hazard ratios (AHRs) with 95% CIs, controlling for age, sex, income, urbanization, health care use, and comorbidity. Results: The study included 11 427 individuals with BD-II (mean [SD] age, 39.6 [16.6] years; 7073 [61.9%] female) and 45 708 matched controls (mean [SD], 39.6 [16.7] years; 28 292 [61.9%] female). During a mean (SD) follow-up of 7.3 (5.1) years, 1089 patients with BD-II and 1879 controls died (AHR, 1.62; 95% CI, 1.47-1.78). Excess mortality in BD-II was observed for natural causes (AHR, 1.37; 95% CI, 1.23-1.52) and for unnatural causes (AHR, 4.46; 95% CI, 3.53-5.64). Natural-cause deaths included mental and behavioral disorders; circulatory, respiratory, digestive, and skin or subcutaneous diseases; and symptoms, signs, and abnormal clinical and laboratory findings not elsewhere classified. Unnatural-cause deaths were predominantly unintentional injuries, suicide, and assault or homicide. Findings were consistent across sex, age, and psychiatric comorbidities. In within-family analyses, BD-II remained associated with higher all-cause (AHR, 1.31; 95% CI, 1.00-1.72) and unnatural-cause mortality (AHR, 2.05; 95% CI, 1.43-2.95) but not natural-cause mortality. Compared with BD-I, BD-II had higher all-cause (AHR, 1.24; 95% CI, 1.01-1.53) and natural-cause mortality (AHR, 1.45; 95% CI, 1.14-1.86) but not unnatural-cause mortality. Conclusions and Relevance: In this cohort study, BD-II was associated with a significant risk of premature mortality across multiple causes; even after accounting for shared familial factors and relative to BD-I, all-cause mortality remained elevated. These findings underscore the importance of comprehensive psychiatric care for individuals with BD-II.