All-cause and cause-specific mortality among people with bipolar disorder: a large-scale systematic review and meta-analysis

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Abstract
Objective: Bipolar disorder (BD) is associated with premature mortality. All-cause and specific mortality risks in this population remain unclear, and more studies are still needed to further understand this issue and guide individual and public strategies to prevent mortality in bipolar disorder Thus, a systematic review and meta‐analysis of studies assessing mortality risk in people with BD versus the general population was conducted. The primary outcome was all‐cause mortality, whilst secondary outcomes were mortality due to suicide, natural, unnatural, and specific‐causes mortality. Results: Fifty-seven studies were included (BD; n = 678,353). All‐cause mortality was increased in people with BD (RR = 2.02, 95% CI: 1.89–2.16, k = 39). Specific‐cause mortality was highest for suicide (RR = 11.69, 95% CI: 9.22–14.81, k = 25). Risk of death due to unnatural causes (RR = 7.29, 95% CI: 6.41–8.28, k = 17) and natural causes (RR = 1.90, 95% CI: 1.75–2.06, k = 17) were also increased. Among specific natural causes analyzed, infectious causes had the higher RR (RR = 4,38, 95%CI: 1.5–12.69, k = 3), but the analysis was limited by the inclusion of few studies. Mortality risk due to respiratory (RR = 3.18, 95% CI: 2.55–3.96, k = 6), cardiovascular (RR = 1.76, 95% CI: 1.53–2.01, k = 27), and cerebrovascular (RR = 1.57, 95% CI: 1.34–1.84, k = 13) causes were increased as well. No difference was identified in mortality by cancer (RR = 0.99, 95% CI: 0.88–1.11, k = 16). Subgroup analyses and meta-regression did not affect the findings. Conclusion: Results presented in this meta-analysis show that risk of premature death in BD is not only due to suicide and unnatural causes, but somatic comorbidities are also implicated. Not only the prevention of suicide, but also the promotion of physical health and the prevention of physical conditions in individuals with BD may mitigate the premature mortality in this population. Notwithstanding this is to our knowledge the largest synthesis of evidence on BD-related mortality, further well-designed studies are still warranted to inform this field.

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