Frontiers in neurology · 2026
Association of lithium versus valproate initiation with all-cause mortality and incident dementia: a multinational real-world cohort study.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Hou Da-Han, Wu Yu-Hsien, Wu Ming-Ju, Huang Shiau-Shian, Hou Po-Hsun
Аннотация
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSION: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSION: 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.