Chen-Chia Lan1,2, Chia-Chien Liu3,4, Ching-Heng Lin5, Tzuo-Yun Lan6, Melvin G McInnis7, Chin-Hong Chan8, Tsuo-Hung Lan2,5,8,9,10. 1. Division of Psychiatry, Taipei Municipal Gan-Dau Hospital, Taipei, Taiwan. 2. Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan. 3. Department of Psychiatry, National Yang-Ming University Hospital, Yilan, Taiwan. 4. Institute of Neuroscience, National Yang-Ming University, Taipei, Taiwan. 5. Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan. 6. Institute of Hospital Management, National Yang-Ming University, Taipei, Taiwan. 7. Department of Psychiatry, University of Michigan School of Medicine, Ann Arbor, MI, USA. 8. Department of Psychiatry, Taichung Veterans General Hospital, Taichung, Taiwan. 9. Department of Psychiatry, National Yang-Ming University, Taipei, Taiwan. 10. Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli, Taiwan.
Abstract
OBJECTIVES: The risk of stroke is increased in patients with bipolar disorder. Lithium exhibits neuroprotective effects but the association between lithium use and the risk of stroke is unknown. METHODS: A population-based retrospective cohort study was conducted by utilizing the National Health Insurance Research Database in Taiwan. Subjects who had first been diagnosed with bipolar disorder between 2001 and 2006 were identified. A propensity score (PS) for receiving lithium was calculated with variables of age, gender, and comorbidities. The patients with bipolar disorder receiving lithium within the period from diagnosis through to December 2011 were designated as the lithium group (n = 635). A 1:2 ratio was used to select PS-matched subjects with bipolar disorder without lithium use (n = 1,250). Multivariate Cox proportional hazards regression models were used to explore the association, rather than causal inference, of lithium exposure and the risk of stroke. RESULTS: Of the 1,885 subjects, 86 (4.6%) experienced stroke, including 2.8% of the lithium group and 5.4% of the non-lithium group. Lithium use was associated with a significantly reduced risk of stroke [hazard ratio (HR) = 0.39, 95% confidence interval (CI): 0.22-0.68]. Reduced risks of stroke were also associated with the highest cumulative lithium dose [≥720 defined daily dose (DDD), HR = 0.25, 95% CI: 0.10-0.59], the longest cumulative exposure period (≥720 days, HR = 0.20, 95% CI: 0.06-0.64), and the highest exposure rate (≥2 DDD/day, HR = 0.39, 95% CI: 0.21-0.70). CONCLUSIONS: Lithium use was significantly related to a reduced risk of stroke in patients with bipolar disorder.
OBJECTIVES: The risk of stroke is increased in patients with bipolar disorder. Lithium exhibits neuroprotective effects but the association between lithium use and the risk of stroke is unknown. METHODS: A population-based retrospective cohort study was conducted by utilizing the National Health Insurance Research Database in Taiwan. Subjects who had first been diagnosed with bipolar disorder between 2001 and 2006 were identified. A propensity score (PS) for receiving lithium was calculated with variables of age, gender, and comorbidities. The patients with bipolar disorder receiving lithium within the period from diagnosis through to December 2011 were designated as the lithium group (n = 635). A 1:2 ratio was used to select PS-matched subjects with bipolar disorder without lithium use (n = 1,250). Multivariate Cox proportional hazards regression models were used to explore the association, rather than causal inference, of lithium exposure and the risk of stroke. RESULTS: Of the 1,885 subjects, 86 (4.6%) experienced stroke, including 2.8% of the lithium group and 5.4% of the non-lithium group. Lithium use was associated with a significantly reduced risk of stroke [hazard ratio (HR) = 0.39, 95% confidence interval (CI): 0.22-0.68]. Reduced risks of stroke were also associated with the highest cumulative lithium dose [≥720 defined daily dose (DDD), HR = 0.25, 95% CI: 0.10-0.59], the longest cumulative exposure period (≥720 days, HR = 0.20, 95% CI: 0.06-0.64), and the highest exposure rate (≥2 DDD/day, HR = 0.39, 95% CI: 0.21-0.70). CONCLUSIONS:Lithium use was significantly related to a reduced risk of stroke in patients with bipolar disorder.
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