A reduced risk of stroke with lithium exposure in bipolar disorder: a population‐based retrospective cohort study
Open accessAbstract
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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In a Taiwanese population-based retrospective cohort of 1 million people, lithium treatment for BD was associated with reduced risk of both stroke and cancer compared to propensity-matched controls.
“Two studies from a random sample of 1 million people, taken from a large population‐based retrospective cohort in Taiwan, demonstrated a reduced risk of both stroke and cancer associated with lithium treatment for BD. The lithium group was compared with propensity‐matched controls.”
From Canadian Network for Mood and Anxiety Treatments ( <scp>CANMAT</scp> ) and International Society for Bipolar Disorders ( <scp>ISBD</scp> ) 2018 guidelines for the management of patients with bipolar disorder (2018) · cites this paper as [794]
The Database section describes a random Taiwanese sample of 1 million people, and the Results and Abstract report a lower stroke risk associated with lithium among patients with bipolar disorder compared with propensity-score-matched nonusers. This paper does not report a cancer-risk finding, so it does not support the claim about both stroke and cancer. (LLM, conf=0.90)
Experimental — accuracy not yet measuredThe reduced risk of stroke with lithium was correlated with higher dose, longer treatment duration, and higher rate of exposure to lithium.
“The reduced risk was also correlated with a higher dose, longer treatment duration and a higher rate of exposure to lithium.794”
In the first study, lithium prescription was associated with a hazard ratio for stroke over 11 years of 0.39 (95% CI 0.22-0.68), even when adjusting for typical and atypical antipsychotics.
“The first study reported hazard ratio for stroke over 11 years of 0.39 (95% CI 0.22‐0.68) for those prescribed lithium, even when adjusting for the risks associated with typical and atypical antipsychotics.”
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Cites
LITHIUM SALTS IN THE TREATMENT OF PSYCHOTIC EXCITEMENT
Cade, J. F. (1949) · The Medical Journal of Australia · doi:10.5694/j.1326-5377.1949.tb36912.x · Cited by 1,456 · see citing works
The multifaceted roles of glycogen synthase kinase 3β in cellular signaling
Grimes, C. A., & Jope, R. S. (2001) · Progress in Neurobiology · doi:10.1016/s0301-0082(01)00011-9 · Cited by 1,429 · see citing works
Lithium salts in the treatment of psychotic excitement
Cade, J. F. (1999) · Australian & New Zealand Journal of Psychiatry · doi:10.1080/j.1440-1614.1999.06241.x · Cited by 1,146 · see citing works
Lithium induces autophagy by inhibiting inositol monophosphatase
Sarkar, S., Floto, R. A., Berger, Z., Imarisio, S., Cordenier, A., Pasco, M., Cook, L. J., & Rubinsztein, D. C. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200504035 · Cited by 985 · see citing works
The vascular smooth muscle cell in arterial pathology: a cell that can take on multiple roles
Lacolley, P. J., Regnault, V., Nicoletti, A., Li, Z., & Michel, J. (2012) · Cardiovascular Research · doi:10.1093/cvr/cvs135 · Cited by 698 · see citing works
Epidemiology and the Global Burden of Stroke
Mukherjee, D. R., & Patil, C. G. (2011) · World Neurosurgery · doi:10.1016/j.wneu.2011.07.023 · Cited by 648 · see citing works
Nonaka, S., Hough, C. J., & Chuang, D. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.5.2642 · Cited by 430 · see citing works
Dong, J.-Y., Zhang, Y., Tong, J., & Qin, L. (2011) · Stroke · doi:10.1161/strokeaha.111.630871 · Cited by 328 · see citing works
Greater Cortical Gray Matter Density in Lithium-Treated Patients with Bipolar Disorder
Bearden, C. E., Thompson, P. M., Dalwani, M., Hayashi, K. M., Lee, A. D., Nicoletti, M., Trakhtenbroit, M., Glahn, D. C., Brambilla, P., Sassi, R. B., et al. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.10.027 · Cited by 289 · see citing works
Atypical Antipsychotics and Risk of Cerebrovascular Accidents
Herrmann, N., Mamdani, M., & Lanctôt, K. L. (2004) · American Journal of Psychiatry · doi:10.1176/appi.ajp.161.6.1113 · Cited by 274 · see citing works
Increased gray matter volume in lithium-treated bipolar disorder patients
Sassi, R. B., Nicoletti, M., Brambilla, P., Mallinger, A. G., Frank, E., Kupfer, D. J., Keshavan, M. S., & Soares, J. C. (2002) · Neuroscience Letters · doi:10.1016/s0304-3940(02)00615-8 · Cited by 263 · see citing works
Hashimoto, R., Takei, N., Shimazu, K., Christ, L. A., Lu, B., & Chuang, D. (2002) · Neuropharmacology · doi:10.1016/s0028-3908(02)00217-4 · Cited by 257 · see citing works
Neuroprotective effects of chronic lithium on focal cerebral ischemia in rats
Nonaka, S., & Chuang, D. (1998) · Neuroreport · doi:10.1097/00001756-199806220-00031 · Cited by 250 · see citing works
Atherosclerosis and proteinase activation
DOLLERY, C. M., & Libby, P. (2005) · Cardiovascular Research · doi:10.1016/j.cardiores.2005.11.003 · Cited by 249 · see citing works
Novel Insights into Lithium’s Mechanism of Action: Neurotrophic and Neuroprotective Effects
Quiroz, J. A., Machado‐Vieira, R., Zarate, C. A., & Manji, H. K. (2010) · Neuropsychobiology · doi:10.1159/000314310 · Cited by 225 · see citing works
Ren, M., Senatorov, V. V., Chen, R., & Chuang, D. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0937423100 · Cited by 206 · see citing works
Stroke: Morbidity, Risk Factors, and Care in Taiwan
Hsieh, F., & Chiou, H. (2014) · Journal of Stroke · doi:10.5853/jos.2014.16.2.59 · Cited by 173 · see citing works
Chuang, D., Wang, Z., & Chiu, C. (2011) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2011.00015 · Cited by 171 · see citing works
Xu, J., Čulman, J., Blume, A., Brecht, S., & Gohlke, P. (2003) · Stroke · doi:10.1161/01.str.0000066308.25088.64 · Cited by 165 · see citing works
Olesen, J. B., Abildstrom, S. Z., Erdal, J., Gislason, G., Weeke, P. E., Andersson, C., Torp-Pedersen, C. T., & Hansen, P. R. (2011) · Pharmacoepidemiology and Drug Safety · doi:10.1002/pds.2186 · Cited by 140 · see citing works
Yu, F., Wang, Z., Tchantchou, F., Chiu, C., Zhang, Y., & Chuang, D. (2011) · Journal of Neurotrauma · doi:10.1089/neu.2011.1942 · Cited by 138 · see citing works
Chang, C., Liao, C.-H., Lin, C., Lane, H., Sung, F., & Kao, C.-H. (2014) · Seizure · doi:10.1016/j.seizure.2014.02.007 · Cited by 107 · see citing works
Self-citationPrieto, M. L., Barboza, A. B. C., Bobo, W. V., Roger, V. L., Bellivier, F., Leboyer, M., West, C. P., & Frye, M. A. (2014) · Acta Psychiatrica Scandinavica · doi:10.1111/acps.12293 · Cited by 98 · see citing works
Olesen, J. B., Hansen, P. R., Abildstrom, S. Z., Andersson, C., Weeke, P. E., Schmiegelow, M., Erdal, J., Torp-Pedersen, C. T., & Gislason, G. (2010) · Pharmacoepidemiology and Drug Safety · doi:10.1002/pds.2073 · Cited by 88 · see citing works
Lithium Upregulates Vascular Endothelial Growth Factor in Brain Endothelial Cells and Astrocytes
Guo, S., Arai, K., Stins, M. F., Chuang, D., & Lo, E. H. (2008) · Stroke · doi:10.1161/strokeaha.108.524504 · Cited by 86 · see citing works
Pathophysiological Mechanisms of Carotid Plaque Vulnerability: Impact on Ischemic Stroke
Pelisek, J., Eckstein, H., & Zernecke, A. (2012) · Archivum Immunologiae et Therapiae Experimentalis · doi:10.1007/s00005-012-0192-z · Cited by 79 · see citing works
Rej, S., Beaulieu, S., Segal, M., Low, N. C. P., Mucsi, I., Holcroft, C., Shulman, K. I., & Looper, K. J. (2014) · Drugs & Aging · doi:10.1007/s40266-014-0221-1 · Cited by 71 · see citing works
Effectiveness of Lithium Carbonate in the Treatment of Manic-Depressive Illness
VELDE, C. D. V. D. (1970) · American Journal of Psychiatry · doi:10.1176/ajp.127.3.345 · Cited by 71 · see citing works
Lin, H., Tsai, S., & Lee, H. (2006) · Journal of Affective Disorders · doi:10.1016/j.jad.2006.09.016 · Cited by 71 · see citing works
Choi, S., Jang, H.-J., KANG, Y. Y., Jung, J. G., Han, S. J., Kim, H. J., Kim, D. J., & Lee, K. W. (2010) · Vascular Pharmacology · doi:10.1016/j.vph.2010.09.004 · Cited by 59 · see citing works
Second-Generation Antipsychotics and Risk of Cerebrovascular Accidents in the Elderly
Percudani, M., Barbui, C., Fortino, I., Tansella, M., & Petrovich, L. (2005) · Journal of Clinical Psychopharmacology · doi:10.1097/01.jcp.0000178414.14685.c4 · Cited by 59 · see citing works
Chronic Kidney Disease and Stroke
Husseini, N. E., Kaskar, O. B., & Goldstein, L. B. (2014) · Advances in Chronic Kidney Disease · doi:10.1053/j.ackd.2014.09.001 · Cited by 57 · see citing works
Tsai, K., Lee, C., Chou, Y.-M., Su, C., & Chou, F. H. (2012) · Schizophrenia Research · doi:10.1016/j.schres.2012.02.013 · Cited by 54 · see citing works
The Effect of Lithium in Post-Stroke Motor Recovery
Mohammadianinejad, S. E., Majdinasab, N., Sajedi, S. A., Abdollahi, F., Moqaddam, M. M., & Sadr, F. (2014) · Clinical Neuropharmacology · doi:10.1097/wnf.0000000000000028 · Cited by 50 · see citing works
Lithium pretreatment reduces brain injury after intracerebral hemorrhage in rats
Kang, K., Kim, Y., Kim, Y., Roh, J.-K., Nam, J.-M., Kim, P.-Y., Ryu, W.-S., Lee, S.-H., & Bw, Y. (2012) · Neurological Research · doi:10.1179/1743132812y.0000000015 · Cited by 48 · see citing works
Ho‐Tin‐Noé, B., & Michel, J. (2011) · Trends in Cardiovascular Medicine · doi:10.1016/j.tcm.2012.05.007 · Cited by 46 · see citing works
Meyer, I. D., Martinet, W., Hove, C. E. V., Schrijvers, D. M., Hoymans, V. Y., Vaeck, L. V., Fransen, P. F., Bult, H., & Meyer, G. R. Y. D. (2010) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2010.01152.x · Cited by 42 · see citing works
Wang, Z., Zhang, X., Chen, S., Wang, D., Wu, J., Liang, T., & Liu, C. (2013) · PLoS ONE · doi:10.1371/journal.pone.0055471 · Cited by 41 · see citing works
Self-citationLaredo, L., Vargas, E., Blasco, A. J., Aguilar, M. D., Moreno, A., & Portolés, A. (2011) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2011.03479.x · Cited by 38 · see citing works
Wu, H.-C., Chou, F. H.-C., Tsai, K.-Y., Su, C.-Y., Shen, S.-P., & Chung, T.-C. (2013) · PLoS ONE · doi:10.1371/journal.pone.0073037 · Cited by 27 · see citing works
Use of Antipsychotics and Risk of Cerebrovascular Events in Schizophrenic Patients
Hsieh, P.-H., Hsiao, F., Gau, S. S., & Gau, C. (2013) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0b013e3182900dfe · Cited by 26 · see citing works
Kim, S., Bong, N., Kim, O. S., Jin, J., Kim, D., & Lee, D. (2014) · Cell Biology International · doi:10.1002/cbin.10352 · Cited by 19 · see citing works
Xu, J., Scholz, A., Rösch, N., Blume, A., Unger, T., Kreutz, R. H., Čulman, J., & Gohlke, P. (2005) · Journal of Hypertension · doi:10.1097/01.hjh.0000189868.48290.d8 · Cited by 15 · see citing works
Antipsychotics Prescription and Cerebrovascular Events in Italian Older Persons
Franchi, C., Sequi, M., Tettamanti, M., Bonometti, F. N., Nobili, A., Fortino, I., Bortolotti, A., Merlino, L. G., Pasina, L., Djade, C. D., et al. (2013) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0b013e3182968fda · Cited by 11 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- [25]25. Dollery CM, Libby P. Atherosclerosis and proteinase acti- vation. Cardiovasc Res 2006; 69: 625-635.
- [39]39. Franchi C, Sequi M, Tettamanti M et al. Antipsy- chotics prescription and cerebrovascular events in Ital- ian older persons. J Clin Psychopharmacol 2013; 33: 542-545.
Cited by
Sorted by citations
Yatham, L. N., Kennedy, S. H., Parikh, S. V., Schaffer, A., Bond, D. J., Frey, B. N., Sharma, V., Goldstein, B. I., Rej, S., Beaulieu, S., et al. (2018) · Bipolar Disorders · doi:10.1111/bdi.12609 · Cited by 1,852 · see citing works
Correll, C. U., Solmi, M., Veronese, N., Bortolato, B., Rosson, S., Santonastaso, P., Thapa‐Chhetri, N., Fornaro, M., Gallicchio, D., Collantoni, E., et al. (2017) · World Psychiatry · doi:10.1002/wps.20420 · Cited by 1,729 · see citing works
Network-based approach to prediction and population-based validation of in silico drug repurposing
Cheng, F., Desai, R. J., Handy, D. E., Wang, R., Schneeweiss, S., Barabási, A.-L., & Loscalzo, J. (2018) · Nature Communications · doi:10.1038/s41467-018-05116-5 · Cited by 552 · see citing works
Yu, S. P., Jiang, M. Q., Shim, S. S., Pourkhodadad, S., & Wei, L. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00636-1 · Cited by 165 · see citing works
Innovative approaches to bipolar disorder and its treatment
Harrison, P. J., Cipriani, A., Harmer, C. J., Nobre, A. C., Saunders, K. E. A., Goodwin, G. M., & Geddes, J. R. (2016) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13048 · Cited by 114 · see citing works
Oxidative Stress and the Neurovascular Unit
Rinaldi, C., Donato, L., Alibrandi, S., Scimone, C., D’Angelo, R., & Sidoti, A. (2021) · Life · doi:10.3390/life11080767 · Cited by 71 · see citing works
“One clinical study demonstrated that lithium exposure in bipolar disorder determines a reduced risk of stroke, potentially being able to protect the endothelium and NVU [58].”
BackgroundZivkovic, S., Koh, C. H., Kaza, N., & Jackson, C. A. (2019) · BMC Psychiatry · doi:10.1186/s12888-019-2177-5 · Cited by 65 · see citing works
New Advances in the Pharmacology and Toxicology of Lithium: A Neurobiologically Oriented Overview
Bortolozzi, A. A., Fico, G., Berk, M., Solmi, M., Fornaro, M., Quevedo, J., Zarate, C. A., Kessing, L. V., Vieta, E., & Carvalho, A. F. (2024) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000007 · Cited by 63 · see citing works
Using Lithium in Older Age Bipolar Disorder: Special Considerations
Soh, J. F., Klil‐Drori, S., & Rej, S. (2019) · Drugs & Aging · doi:10.1007/s40266-018-0628-1 · Cited by 60 · see citing works
Anmella, G., Fico, G., Lotfaliany, M., Hidalgo‐Mazzei, D., Soto-Angona, Ó., Giménez‐Palomo, A., Amoretti, S., Murru, A., Raduà, J., Solanes, A., et al. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.03.034 · Cited by 55 · see citing works
Proton magnetic resonance spectroscopy changes after lithium treatment. Systematic review
Szulc, A., Więdłocha, M., Waszkiewicz, N., Galińska-Skok, B., Marcinowicz, P., Gierus, J., & Mosiołek, A. (2018) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2018.01.001 · Cited by 44 · see citing works
Lithium beyond psychiatric indications: the reincarnation of a new old drug
Haupt, M., Bähr, M., & Doeppner, T. R. (2021) · Neural Regeneration Research · doi:10.4103/1673-5374.313015 · Cited by 43 · see citing works
“Clinical stroke studies In addition to the aforementioned preclinical studies, data from two clinical trials are available investigating the retrospective risk of patients treated with lithium (Lan et al., 2015) as well as examining the prospective motor recovery in stroke patients receiving lithium treatment (Abdolla…”
BackgroundChen, P., Tsai, S., Chen, P., Pan, C., Su, S., Chen, C., & Kuo, C. (2022) · Acta Psychiatrica Scandinavica · doi:10.1111/acps.13519 · Cited by 37 · see citing works
“For instance, clinical studies have revealed that lithium treatment reduces the risk of cardiovascular disease in patients with bipolar disorder.(26,34,35) In addition, laboratory studies have indicated that lithium administered at therapeutic levels ameliorates pathological hypertrophy and cardiac fibrogenesis in cel…”
BackgroundBosche, B., Molčányi, M., Rej, S., Doeppner, T. R., Obermann, M., Müller, D. J., Das, A., Hescheler, J., Macdonald, R. L., Noll, T., et al. (2016) · Frontiers in Physiology · doi:10.3389/fphys.2016.00593 · Cited by 33 · see citing works
“Lithium treatment (Rajkowska, 2000; Lan et al., 2015) may be effective in both ischemic and hemorrhagic stroke, and even traumatic brain injury (Leeds et al.”
InfluentialMood stabilisers and risk of stroke in bipolar disorder
Chen, P., Tsai, S., Pan, C., Chang, C.-K., Su, S., Chen, C.-C., & Kuo, C. (2018) · The British Journal of Psychiatry · doi:10.1192/bjp.2018.203 · Cited by 30 · see citing works
Chen, P., Hsiao, C., Chiang, S.-J., Shen, R.-S., Lin, Y., Chung, K., & Tsai, S. (2021) · Australian & New Zealand Journal of Psychiatry · doi:10.1177/00048674211062532 · Cited by 30 · see citing works
“Of particular note, emerging clinical data have suggested that lithium therapy reduces the risk of cardiovascular disease in patients with bipolar disorder (Lan et al., 2015; Prosser and Fieve, 2016; Tsai et al., 2020).”
BackgroundBosche, B., Molčányi, M., Noll, T., Rej, S., Zatschler, B., Doeppner, T. R., Hescheler, J., Müller, D. J., Macdonald, R. L., & Härtel, F. V. (2016) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2016.02.004 · Cited by 27 · see citing works
“This concept is supported by recent studies showing that lithium-associated preconditioning reduces the risk of stroke in bipolar disorder patients (Lan et al., 2015) and may support functional recovery after cortical stroke (Mohammadianinejad et al., 2014).”
BackgroundResultShuy, Y. K., Santharan, S., Chew, Q. H., & Sim, K. (2024) · Brain Sciences · doi:10.3390/brainsci14010102 · Cited by 26 · see citing works
“Apart from its positive effects on clinical outcomes, lithium was associated with lower risks of cancer [48], a reduced risk of stroke [53], and insulin resistance [36].”
BackgroundPrillo, J., Soh, J. F., Dols, A., Park, H., Beaulieu, S., Linnaranta, O., & Rej, S. (2021) · BMC Psychiatry · doi:10.1186/s12888-021-03572-w · Cited by 22 · see citing works
Almeida, O. P., Singulani, M. P., Ford, A. H., Hackett, M. L., Etherton‐Beer, C., Flicker, L. A., Hankey, G. J., Paula, V. J. R. D., Penteado, C. T., & Forlenza, O. V. (2022) · Stroke · doi:10.1161/strokeaha.122.039203 · Cited by 21 · see citing works
Wang, D., & Osser, D. N. (2019) · Bipolar Disorders · doi:10.1111/bdi.12860 · Cited by 21 · see citing works
Neuropsychiatric Complications after Stroke
Nemani, K., & Gurin, L. J. (2021) · Seminars in Neurology · doi:10.1055/s-0040-1722723 · Cited by 19 · see citing works
The role of brain barriers in the neurokinetics and pharmacodynamics of lithium
Luo, H., Chevillard, L., Bellivier, F., Mégarbane, B., Étain, B., Cisternino, S., & Declèves, X. (2021) · Pharmacological Research · doi:10.1016/j.phrs.2021.105480 · Cited by 18 · see citing works
Beunders, A. J. M., Kok, A. A. L., Kosmas, P. C., Beekman, A. T. F., Sonnenberg, C., Schouws, S. N. T. M., Kupka, R., Stek, M. L., & Dols, A. (2021) · Journal of Affective Disorders · doi:10.1016/j.jad.2021.03.057 · Cited by 18 · see citing works
Ateş, N., Çağlayan, A., Balçıkanlı, Z., Sertel, E., Beker, M. Ç., Dilsiz, P., Çağlayan, A. B., Celik, S., Dasdelen, M. F., Çağlayan, B., et al. (2022) · Experimental Neurology · doi:10.1016/j.expneurol.2022.113996 · Cited by 18 · see citing works
Chen, P., Chung, C., Lin, Y., Kao, Y., & Chen, Y. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22020842 · Cited by 20 · see citing works
“Moreover, emerging evidence has indicated a decrease in the risk of cardiovascular morbidity and mortality in patients with bipolar disorder after receiving therapeutic lithium [19,20].”
BackgroundVillahoz, S., Yunes-Leites, P. S., Méndez‐Barbero, N., Urso, K., Bonzón‐Kulichenko, E., Ortega, S., Nistal, J. F., Vázquez, J., Offermanns, S., Redondo, J. M., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-07071-7 · Cited by 18 · see citing works
Chen, P., Tsai, S., Pan, C., Chen, Y.-L., Su, S., Chen, C.-C., & Kuo, C. (2021) · Australian & New Zealand Journal of Psychiatry · doi:10.1177/00048674211046891 · Cited by 18 · see citing works
“For instance, lithium is associated with a reduced risk of cerebrovascular diseases and cardiovascular diseases in patients with bipolar disorder (Lan et al., 2015; Prosser and Fieve, 2016), likely through the inhibition of proinflammatory responses, reactive oxidative stress and endothelial…”
BackgroundTsai, S., Shen, R.-S., Kuo, C., Chen, P., Chung, K., Hsiao, C., & Huang, S. (2020) · Australian & New Zealand Journal of Psychiatry · doi:10.1177/0004867420952551 · Cited by 18 · see citing works
“This study provides further evidence for a link between lithium and the decreases in atherosclerosis-related myocardial infarction (Prosser and Fieve, 2016) as well as stroke in BD patients receiving regular lithium therapy (Chen et al., 2019; Lan et al., 2015).”
BackgroundKessing, L. V., Knudsen, M. B., Rytgaard, H. C. W., Torp-Pedersen, C., & Berk, M. (2024) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2024.04.009 · Cited by 16 · see citing works
Chen, P., Hsiao, C., Chiang, S.-J., & Tsai, S. (2022) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.13497 · Cited by 15 · see citing works
Neuroprotective Effect of Lithium Chloride in Rat Model of Cardiac Arrest
Ostrova, I. V., Grebenchikov, O. A., & Golubeva, N. V. (2019) · General Reanimatology · doi:10.15360/1813-9779-2019-3-73-82 · Cited by 14 · see citing works
Lithium Biological Action Mechanisms after Ischemic Stroke
Munteanu, C., Rotariu, M., Turnea, M. A., Tătăranu, L. G., Dogaru, G., Popescu, C., Spînu, A., Andone, I., Ionescu, E. V., Tucmeanu, E.-R., et al. (2022) · Life · doi:10.3390/life12111680 · Cited by 11 · see citing works
“In a study, lithium was shown to reduce the accumulation of atherosclerotic plaque in mice [59].”
BackgroundHigh risk of silent stroke in older bipolar patients with typical‐onset age
Lee, H., Hsu, J., Chen, P., Chung, K., Huang, Y., & Tsai, S. (2019) · Psychogeriatrics · doi:10.1111/psyg.12419 · Cited by 8 · see citing works
Afjeh, S. S. A., Shams, J., Hamednia, S., Boshehri, B., Olfat, A., & Omrani, M. D. (2020) · Pharmacogenomics · doi:10.2217/pgs-2020-0058 · Cited by 8 · see citing works
Cherpakov, R. A., & Grebenchikov, O. A. (2021) · General Reanimatology · doi:10.15360/1813-9779-2021-5-101-110 · Cited by 7 · see citing works
Tai, S., Chao, L., Huang, T., Chang, C. C., Huang, S., Wu, T., & Lee, E.-J. (2021) · Neurological Research · doi:10.1080/01616412.2021.1965427 · Cited by 6 · see citing works
“In a population-based retrospective cohort study, lithium use and accumulation for the treatment of bipolar disorder were associated with a significantly decreased risk of stroke [7].”
BackgroundLithium in cardiovascular health and disease: Pharmacological and clinical implications
Jiang, J., He, W., & Huang, H. (2025) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2025.177657 · Cited by 5 · see citing works
Chen, P., Hsiao, C., Chiang, S.-J., Lin, Y., Chung, K., & Tsai, S. (2025) · Journal of Affective Disorders · doi:10.1016/j.jad.2025.120525 · Cited by 4 · see citing works
Huang, M., Cheng, C., Hsu, J.-W., Bai, Y., Su, T., Li, C., Tsai, S., Chan, Y. E., & Chen, M. (2025) · Acta Psychiatrica Scandinavica · doi:10.1111/acps.70043 · Cited by 3 · see citing works
Lithium for geriatric bipolar mood disorder – gold standard or faux bijoux?
Naguy, A., & Shoukry, T. M. (2019) · Australasian Psychiatry · doi:10.1177/1039856218781021 · Cited by 3 · see citing works
Update – Lithium in der Phasenprophylaxe Bipolarer Störungen
Petzold, J., Bauer, M., & Severus, E. (2018) · Fortschritte der Neurologie · Psychiatrie · doi:10.1055/a-0633-2511 · Cited by 2 · see citing works
Grebenchikov, O. A., Cherpakov, R. A., Evseyev, A. K., Валерьевич, Е. А., Kuzovlev, A. N., Lonchinsky, P. A., Petrikov, S. S., & Курбанович, Ш. А. (2022) · Russian Sklifosovsky Journal Emergency Medical Care · doi:10.23934/2223-9022-2021-10-4-676-686 · Cited by 2 · see citing works
Recommencing lithium in Older Adults with Bipolar I Disorder
Gallur, L., Powell, A., & Flynn, P. (2017) · Australasian Psychiatry · doi:10.1177/1039856217738374 · Cited by 1 · see citing works
Achieving and Maintaining Effective Plasma Concentration of Lithium After Oral Administration
Makarevich, D. G., Grebenchikov, O. A., Yadgarov, M. Y., Бондоевич, Б. Л., Kadantseva, K., & Likhvantsev, V. V. (2023) · General Reanimatology · doi:10.15360/1813-9779-2023-1-2307 · Cited by 1 · see citing works
Special Issue “Pathophysiology and Treatment of Alzheimer’s Disease”
Fessel, J. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25116015 · Cited by 1 · see citing works
“For those with the highest and longest cumulative exposures to lithium, the HR equaled 0.25 and 0.20, respectively [17].”
BackgroundInfluentialLithium in Older Age Bipolar Disorder
Rej, S. (2017) · Springer eBooks · doi:10.1007/978-3-319-48912-4_7
Luca, M., & Luca, A. (2019) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0000000000001166
“Moreover, it should be underlined that an increased risk of stroke, both related and independent to antipsychotic drugs, as well as alterations of lipid metabolism, has been frequently reported among patients with psychiatric illnesses.(12,13) On these grounds, also in the light of Sun and colleagues' interesting find…”
BackgroundResultUrback, A. L. (2017) · TSpace (University of Toronto)
Almeida, J., Spelber, D., & Smith, T. L. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as37
Le lithium dans le traitement des troubles bipolaires
Hennion, V., Masson, M., Cul, A. D., & Bellivier, F. (2023) · Elsevier eBooks · doi:10.1016/b978-2-294-77180-4.00048-2
Association between lithium and arterial atherosclerosis in physically healthy bipolar disorder
Tsai, S., Chang, T.-H., Sajatovic, M., Chen, P., Huang, Y., Hung, S., Chung, K., & Kuo, C. (2026) · Journal of Affective Disorders · doi:10.1016/j.jad.2026.122115
Xu, N., Huan, Y., Deng, Y., Yang, R., Liuyan, Z., Wang, K., Huairong, W., Wu, J., Shuting, X., Chen, Y., et al. (2026) · Journal of Affective Disorders · doi:10.1016/j.jad.2026.122282
Xu, N., Forlenza, O. V., Chen, P., Rej, S., Gildengers, A. G., Almeida, O. P., Blumberg, H. P., Dols, A., Emanuel, J. E., Eyler, L. T., et al. (2026) · Acta Psychiatrica Scandinavica · doi:10.1111/acps.70134
Motta, F. D. D. S., Ruffini, M. D. L., Ritter, A. C., Ferrão, S. M., Silva, R. S., Mastella, N. D. S., Montezano, B. B., Ajub, E., Kapczinski, F. P., Pinto, J. V., et al. (2026) · Acta Psychiatrica Scandinavica · doi:10.1111/acps.70151
- Authors
- Lan, C., Liu, C., Lin, C., Lan, T., McInnis, M. G., Chan, C., & Lan, T.
- Affiliations
- National Yang Ming University (TW)
- National Yang Ming University Hospital (TW)
- Taichung Veterans General Hospital (TW)
- National Health Research Institutes (TW)
- University of Michigan (US)
- Corresponding author
- Lan, Tsuo‐Hung
- Venue
- Bipolar Disorders
- Publisher
- Wiley
- Published
- 2015-09-23
- Volume
- 17
- Issue
- 7
- Pages
- 705-714
- ISSN
- 1398-5647 (ISSN-L)
- 1399-5618
- OpenAlex
- W2114651468
- Cited by
- 56
- References
- 44
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 5 · 2023: 3 · 2022: 7 · 2021: 12 · 2020: 2 · 2019: 7 · 2018: 6 · 2017: 4 · 2016: 3
- FWCI
- 3.51
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Locations
- Bipolar Disorders (publishedVersion)
- PubMed (publishedVersion)
- Deep Blue (University of Michigan) (submittedVersion)
- Funders
- Taichung Veterans General Hospital, Taichung, Taiwan (TCVGH-101-1102)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- lithium, bipolar disorder, stroke risk, neuroprotection, antipsychotic safety, propensity score matching
- MeSH terms
- Adult, Bipolar Disorder, Female, Humans, Male, Middle Aged, Psychotropic Drugs, Retrospective Studies, Taiwan, Cohort Studies, Incidence, Proportional Hazards Models, Databases, Factual, Lithium Compounds, Neuroprotective Agents, Stroke
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