A New Risk with Bipolar II

Surprisingly, Bipolar II carries a higher mortality risk than Bipolar I

STUDY: Hsu CW et al, JAMA Netw Open 2026;9(4):e265535

STUDY TYPE: Population-based retrospective cohort study

FUNDING: Taiwan National Science and Technology Council

Background

Bipolar II may lack the mania of bipolar I, but these patients spend half of their lives in depression, in contrast to a third of the lifespan for bipolar I. The bipolar nature of their depressions is often missed, leading to years of untreated psychological pain. This study tells us there is a physical toll as well.

The Study

This nationwide cohort study used Taiwan’s health insurance database to follow 11,427 adults with Bipolar II and 45,708 matched controls for an average of 7.3 years. All-cause mortality, natural-cause mortality, and unnatural-cause mortality were compared across matched controls, unaffected siblings, and a Bipolar I cohort of nearly 180,000 patients.

Patients with Bipolar II were 62% more likely to die from any cause than matched controls (adjusted hazard ratio [AHR] 1.62). Natural-cause mortality was 37% higher, spanning circulatory, respiratory, digestive, and other diseases. The more striking finding was “unnatural-cause” mortality (ie, accidents and suicide) — more than fourfold higher overall (AHR 4.46), driven largely by suicide (AHR 6.16) and unintentional injury (AHR 2.81). However, suicide rates didn’t differ between the two subtypes.

In sibling analyses that controlled for shared family environment and genetics, the elevated all-cause and suicide mortality held. Compared directly with Bipolar I, patients with Bipolar II actually had higher all-cause mortality (AHR 1.24) and higher natural-cause mortality (AHR 1.45) — despite similar medical comorbidity at baseline.

Practice Implications

1. Earlier studies found high mortality with Bipolar I, which takes an average of 10 years off the lifespan (mostly due to cardiovascular disease, followed by metabolic, respiratory, cancer, and suicide). The problem may be worse for Bipolar II.
2. Think about mortality risk when choosing medications. Stroke is the #1 cause of death in bipolar disorder, and lithium and lamotrigine are the only mood stabilizers that due not raise the stroke risk (lithium may lower it).
3. The good news is that lithium and anticonvulsant-mood stabilizers lower mortality in bipolar disorder. Lithium — which has antiaging and antisuicide effects — has the strongest effects there.