2026-10-14T21:35:49Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33961393 2026-09-22T04:18:11Z category_363 portal_316 item_type_3 month_year_09_2026

Supplementary file 1_Association of lithium versus valproate initiation with all-cause mortality and incident dementia: a multinational real-world cohort study.docx Da-Han Hou (21485149) Yu-Hsien Wu (1601986) Ming-Ju Wu (454092) Shiau-Shian Huang (16728790) Po-Hsun Hou (6736904) Neurology and Neuromuscular Diseases dementia lithium mortality real-world evidence valproate Background<p>Lithium and valproate are widely prescribed mood stabilizers, but their comparative long-term associations with mortality and dementia remain uncertain. We compared the risks of all-cause mortality and incident dementia among adults initiating lithium or valproate using a large multinational electronic health record network.</p>Methods<p>We conducted a retrospective cohort study using the TriNetX Global Collaborative Network (2004–2024), a multinational electronic health record network. Adults aged ≥40 years initiating lithium or valproate were identified after excluding patients with pre-existing dementia, epilepsy, intracranial injury, kidney transplantation, advanced chronic kidney disease, or acute kidney injury. The primary analysis followed an intention-to-treat approach based on the first recorded prescription of lithium or valproate. Propensity score matching incorporated demographic, clinical, psychiatric, and treatment-related characteristics, resulting in 22,098 patients in each treatment group. A 30-day prescription-confirmed analysis and lag-time analyses were performed as supportive and sensitivity analyses, respectively.</p>Results<p>During follow-up, 884 deaths occurred among lithium initiators and 1,585 among valproate initiators. The corresponding five-year Kaplan–Meier-estimated cumulative event probabilities for all-cause mortality were 6.61 and 10.65%, respectively. Lithium initiation was associated with a lower recorded risk of all-cause mortality than valproate initiation [hazard ratio (HR) 0.58, 95% confidence interval (CI) 0.53–0.63; p < 0.001]. Incident dementia occurred in 495 lithium initiators and 754 valproate initiators, with corresponding five-year Kaplan–Meier-estimated cumulative event probabilities of 3.51 and 4.85%, respectively. Lithium initiation was also associated with a lower recorded risk of incident dementia (HR 0.68, 95% CI 0.60–0.76; p < 0.001). Findings remained directionally consistent in the supportive prescription-confirmed and lag-time analyses.</p>Conclusion<p>Lithium initiation was associated with lower recorded risks of all-cause mortality and incident dementia than valproate initiation. These associations remained directionally consistent across supportive and sensitivity analyses, although residual confounding inherent to observational studies cannot be excluded.</p> 2026-09-22T04:18:11Z Dataset Dataset 10.3389/fneur.2026.1847655.s001 https://figshare.com/articles/dataset/Supplementary_file_1_Association_of_lithium_versus_valproate_initiation_with_all-cause_mortality_and_incident_dementia_a_multinational_real-world_cohort_study_docx/33961393 CC BY 4.0