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

Authors

• Chih-Wei Hsu
• Yang-Chieh Brian Chen
• Edward Chia-Cheng Lai
• Andrew A Nierenberg
• Michael Berk
• Sheng-Yu Lee
• Liang-Jen Wang
• Mu-Hong Chen
• Yao-Hsu Yang
• Chih-Sung Liang
• Andre F Carvalho

Language

English

Publication Date

4-1-2026

Journal

JAMA Network Open

DOI

10.1001/jamanetworkopen.2026.5535

PMID

41945344

PMCID

PMC13058765

PubMedCentral® Posted Date

4-7-2026

PubMedCentral® Full Text Version

Post-print

Abstract

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.

Keywords

Retrospective Studies, Cause of Death, Bipolar Disorder, Taiwan, Databases, Factual, Case-Control Studies, Humans, Male, Female, Child, Adolescent, Young Adult, Adult, Middle Aged, Mortality, Premature, Proportional Hazards Models

Published Open-Access

yes

Recommended Citation

Hsu, Chih-Wei; Chen, Yang-Chieh Brian; Lai, Edward Chia-Cheng; et al., "All-Cause and Cause-Specific Mortality in Patients With Bipolar II Disorder" (2026). Children’s Nutrition Research Center Staff Publications. 410.
https://digitalcommons.library.tmc.edu/staff_pub/410