Comorbid physical health outcomes in patients with bipolar disorder: An umbrella review of systematic reviews and meta-analyses

Background: Although several meta-analyses have examined the association between bipolar disorder (BD) and its comorbid health outcomes, this evidence has not been comprehensively assembled. Objective: We aimed to systematically review existing meta-analyses based on multiple physical outcomes and validate the evidence level by examining the existing certainty of evidence. Methods: We systematically searched databases, including PubMed/MEDLINE, Embase, Google Scholar, and CINAHL, for articles published up to July 2023. We included meta-analyses of cohort, case-control, and/or crosssectional studies investigating any comorbid health outcomes in patients with BD. We conducted quality assessments of the included meta-analysis using AMSTAR2. The credibility of findings was categorized into five levels of class and quality of evidence (CE), including convincing, highly suggestive, suggestive, weak, or not significant. Results: We analyzed 12 meta-analyses, including 145 original articles, covering 14 unique health outcomes with over 60 million participants across 29 countries and five continents. Among 14 health outcomes, BD was significantly associated with eight comorbid health outcomes, including dementia (equivalent odds ratio [eOR], 2.96 [95 % confidence intervals {CI}, 1.69 -5.17]; CE =suggestive), Parkinson 's disease (3.35 [1.72 -6.53]; CE =suggestive), asthma (1.86 [1.42 -2.42]; CE =weak), toxoplasmosis (1.69 [1.21 -2.37]; CE =weak), hypertension (1.28 [1.02 -1.60]; CE =convincing), breast cancer (1.33 [1.15 -1.55]; CE =weak), obesity (1.64 [1.30 -1.99]; CE =suggestive), and type 2 diabetes mellitus (1.98 [1.55 -2.52]; CE =weak). Conclusion: Individuals with BD are predisposed to numerous comorbid physical conditions, though these links are supported by various evidence levels and necessitate further studies. It is imperative that physicians be aware of these potential comorbidities in patients with BD and take proactive measures to manage them.