Association of lipid-modifying medication with reduced mortality in bipolar disorder: A nationwide cohort study

Patients with bipolar disorder face higher mortality risks from natural causes and suicide. Lipid-modifying medications, among the most widely prescribed medications, also show potential in alleviating mood symptoms. Limited research explores if these medications reduce all-cause, natural, and suicide mortality risks.

This national cohort study, using Taiwan's National Health Insurance Research Database (2001-2022), included 32,479 bipolar disorder patients. Among them, 6800 died (4963 natural causes, 1154 suicide). Standardized Mortality Ratios (SMRs) were calculated, and Hazard Ratios (HRs) for lipid-modifying medications were estimated using multivariable Cox proportional hazards regression with a time-dependent model.

SMRs for all-cause, natural, and suicide mortality in the bipolar cohort were 6.36, 5.28, and 29.07, respectively. Lipid-modifying medications were associated with significantly reduced risks of all-cause (aHR = 0.38, P < .001), natural (aHR = 0.41, P < .001), and suicide mortality (aHR = 0.41, P < .001) within the 5-year follow-up post-index admission. Among the differing classes of lipid-modifying medications, statins and fibrates were linked to lower risks of all-cause (statins: aHR = 0.42, P < .001; fibrates: aHR = 0.49, P < .001), natural mortality (statins: aHR = 0.42, P < .001; fibrates: aHR = 0.59, P = .003), and suicide mortality (statins: aHR = 0.51, P = .002; fibrates: aHR = 0.33, P = .006).

Besides protecting against natural mortality, lipid-modifying medications exhibit salutary associations with suicide and all-cause mortality in bipolar disorder patients. To meaningfully reduce the high mortality rate, future studies should explore the pleiotropic benefits of these medications.

Lipid-modifying medications are widely recommended to treat cardiometabolic diseases and can have therapeutic potentials to improve mood symptoms associated with bipolar disorder. However, few studies have evaluated whether lipid-modifying medications are associated with a decreased risk of mortality from either natural causes or suicide among patients with bipolar disorder. This study found that in addition to having protective effects against natural mortality, lipid-modifying medications exert protective effects against suicide and all-cause mortality among patients with bipolar disorder.