The Association Between Lithium Use and Physical Comorbidities Across Age Groups: A Cross-Sectional Study From the Global Aging and Geriatric Experiments in Bipolar Disorder (GAGE-BD) Project.

INTRODUCTIONS: Lithium remains the first-line maintenance treatment for bipolar disorder (BD), yet its safety in older-age BD (OABD) is uncertain due to limited large-scale data. OABD patients often experience more severe physical comorbidities compared to younger BD patients, but systematic evidence regarding lithium's association with these conditions is lacking. This study examined the association between lithium use and physical comorbidities across age groups using the international Global Aging and Geriatric Experiments in Bipolar Disorder (GAGE-BD) dataset.

METHODS

A cross-sectional analysis was conducted using combined Wave 1 and 2 data from GAGE-BD project, encompassing 37 studies from 20 sites worldwide. Participants aged ≥ 18 years with BD were classified according to current lithium use. Physical comorbidities were harmonised into eight organ-system domains. Sociodemographic and clinical variables were compared between individuals receiving lithium treatment and those not prescribed lithium. Generalised linear mixed models adjusted for age, site and lithium × age interaction were applied to evaluate associations with physical comorbidities.

RESULTS

Of the 2873 total participants included in the study, 1069 were currently receiving lithium treatment and 1804 were not prescribed lithium. Participants treated with lithium showed a lower overall prevalence of physical comorbidities compared with those not receiving lithium. Regression analyses revealed significant age-by-lithium interactions for cardiovascular (χ2 = 9.27, p = 0.002), respiratory (χ2 = 7.56, p = 0.006), genitourinary (χ2 = 8.66, p = 0.003) and endocrine (χ2 = 16.96, p < 0.001) comorbidities. Model-estimated curve crossings occurred at approximately 43 years (cardiovascular), 32 years (respiratory), 51 years (genitourinary) and 59 years (endocrine), above which predicted prevalence was lower among participants treated with lithium, whereas no differences were observed for gastrointestinal, hepatic, renal or musculoskeletal systems.

CONCLUSIONS

Lithium use in OABD was associated with a lower burden of specific physical comorbidities, particularly cardiovascular, respiratory and endocrine conditions. Although prescription bias cannot be excluded, the findings challenge the perception that lithium exacerbates physical health risks in older adults. Instead, they support lithium's continued use-with appropriate monitoring-as a safe and effective treatment option for OABD, and highlight the need for prospective studies to further clarify the relationship between lithium exposure and physical health outcomes.