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Mood stabilisers and risk of stroke in bipolar disorder

  • Pao-Huan Chen (a1), Shang-Ying Tsai (a2), Chun-Hung Pan (a3), Chi-Kang Chang (a4), Sheng-Shiang Su (a5), Chiao-Chicy Chen (a6) and Chian-Jue Kuo (a7)...
Abstract
Background

Research on the risk of stroke following the use of mood stabilisers specific to patients with bipolar disorder is limited.

Aims

In this study, we investigated the risk of stroke following the exposure to mood stabilisers in patients with bipolar disorder.

Method

Data for this nationwide population-based study were derived from the Taiwan National Health Insurance Research Database. Among a retrospective cohort of patients with bipolar disorder (n = 19 433), 609 new-onset cases of stroke were identified from 1999 to 2012. A case–crossover study design utilising 14-day windows was applied to assess the acute exposure effect of individual mood stabilisers on the risk of ischaemic, haemorrhagic and other types of stroke in patients with bipolar disorder.

Results

Mood stabilisers as a group were significantly associated with the increased risk of stroke in patients with bipolar disorder (adjusted risk ratio, 1.26; P = 0.041). Among individual mood stabilisers, acute exposure to carbamazepine had the highest risk of stroke (adjusted risk ratio, 1.68; P = 0.018), particularly the ischaemic type (adjusted risk ratio, 1.81; P = 0.037). In addition, acute exposure to valproic acid elevated the risk of haemorrhagic stroke (adjusted risk ratio, 1.76; P = 0.022). In contrast, acute exposure to lithium and lamotrigine did not significantly increase the risk of any type of stroke.

Conclusions

Use of carbamazepine and valproic acid, but not lithium and lamotrigine, is associated with increased risk of stroke in patients with bipolar disorder.

Declaration of interest

None.

Copyright
Corresponding author
Correspondence: Chian-Jue Kuo, Department of General Psychiatry, Taipei City Psychiatric Center, Taipei City Hospital, 309 Sung-Te Road, Taipei 110, Taiwan. Email: tcpckuo@seed.net.tw
References
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1Sajatovic, M, Strejilevich, SA, Gildengers, AG, Dols, A, Al Jurdi, RK, Forester, BP, et al. A report on older-age bipolar disorder from the International Society for Bipolar Disorders Task Force. Bipolar Disord 2015; 17: 689704.
2Crump, C, Sundquist, K, Winkleby, MA, Sundquist, J. Comorbidities and mortality in bipolar disorder: a Swedish national cohort study. JAMA Psychiatry 2013; 70: 931–9.
3Tsai, SY, Lee, CH, Kuo, CJ, Chen, CC. A retrospective analysis of risk and protective factors for natural death in bipolar disorder. J Clin Psychiatry 2005; 66: 1586–91.
4Correll, CU, Detraux, J, De Lepeleire, J, De Hert, M. Effects of antipsychotics, antidepressants and mood stabilizers on risk for physical diseases in people with schizophrenia, depression and bipolar disorder. World Psychiatry 2015; 14: 119–36.
5Lan, CC, Liu, CC, Lin, CH, Lan, TY, McInnis, MG, Chan, CH, et al. A reduced risk of stroke with lithium exposure in bipolar disorder: a population-based retrospective cohort study. Bipolar Disord 2015; 17: 705–14.
6Prosser, JM, Fieve, RR. Patients receiving lithium therapy have a reduced prevalence of neurological and cardiovascular disorders. Prog Neuropsychopharmacol Biol Psychiatry 2016; 71: 3944.
7Olesen, JB, Abildstrom, SZ, Erdal, J, Gislason, GH, Weeke, P, Andersson, C, et al. Effects of epilepsy and selected antiepileptic drugs on risk of myocardial infarction, stroke, and death in patients with or without previous stroke: a nationwide cohort study. Pharmacoepidemiol Drug Saf 2011; 20: 964–71.
8Chuang, YC, Chuang, HY, Lin, TK, Chang, CC, Lu, CH, Chang, WN, et al. Effects of long-term antiepileptic drug monotherapy on vascular risk factors and atherosclerosis. Epilepsia 2012; 53: 120–8.
9WHO. Manual of the International Statistical Classification of Diseases, Injuries and Causes of Death (9th revision) (ICD-9). World Health Organization, 1977.
10Wu, CS, Wang, SC, Gau, SS, Tsai, HJ, Cheng, YC. Association of stroke with the receptor-binding profiles of antipsychotics-a case-crossover study. Biol Psychiatry 2013; 73: 414–21.
11WHO Collaborating Centre for Drug Statistic Methodology. ATC Index with DDDs. World Health Organization, 2009.
12Charlson, ME, Pompei, P, Ales, KL, MacKenzie, CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987; 40: 373–83.
13Chen, WY, Chen, LY, Liu, HC, Wu, CS, Yang, SY, Pan, CH, et al. Antipsychotic medications and stroke in schizophrenia: a case-crossover study. PLoS One 2017; 12: e0179424.
14Hu, HH, Sheng, WY, Chu, FL, Lan, CF, Chiang, BN. Incidence of stroke in Taiwan. Stroke 1992; 23: 1237–41.
15Lopinto-Khoury, C, Mintzer, S. Antiepileptic drugs and markers of vascular risk. Curr Treat Options Neurol 2010; 12: 300–8.
16Lorenz, MW, Polak, JF, Kavousi, M, Mathiesen, EB, Volzke, H, Tuomainen, TP, et al. Carotid intima-media thickness progression to predict cardiovascular events in the general population (the PROG-IMT collaborative project): a meta-analysis of individual participant data. Lancet 2012; 379: 2053–62.
17Miao, Y, Liao, JK. Potential serum biomarkers in the pathophysiological processes of stroke. Expert Rev Neurother 2014; 14: 173–85.
18Chen, HF, Xu, LP, Luo, ZY, Yu, ZQ, Li, ZY, Cui, QY, et al. Valproic acid-associated low fibrinogen and delayed intracranial hemorrhage: case report and mini literature review. Drug Des Devel Ther 2013; 7: 767–70.
19Nanau, RM, Neuman, MG. Adverse drug reactions induced by valproic acid. Clin Biochem 2013; 46: 1323–38.
20Choi, SE, Jang, HJ, Kang, Y, Jung, JG, Han, SJ, Kim, HJ, et al. Atherosclerosis induced by a high-fat diet is alleviated by lithium chloride via reduction of VCAM expression in ApoE-deficient mice. Vascul Pharmacol 2010; 53: 264–72.
21Wang, Z, Zhang, X, Chen, S, Wang, D, Wu, J, Liang, T, et al. Lithium chloride inhibits vascular smooth muscle cell proliferation and migration and alleviates injury-induced neointimal hyperplasia via induction of PGC-1alpha. PLoS One 2013; 8: e55471.
22Sacchetti, E, Trifiro, G, Caputi, A, Turrina, C, Spina, E, Cricelli, C, et al. Risk of stroke with typical and atypical anti-psychotics: a retrospective cohort study including unexposed subjects. J Psychopharmacol 2008; 22: 3946.
23Zornberg, GL, Jick, H. Antipsychotic drug use and risk of first-time idiopathic venous thromboembolism: a case-control study. Lancet 2000; 356: 1219–23.
24Janicak, PG. The relevance of clinical pharmacokinetics and therapeutic drug monitoring: anticonvulsant mood stabilizers and antipsychotics. J Clin Psychiatry 1993; 54(Suppl): 3541; discussion 55–6.
25Fiedorowicz, JG, Solomon, DA, Endicott, J, Leon, AC, Li, C, Rice, JP, et al. Manic/hypomanic symptom burden and cardiovascular mortality in bipolar disorder. Psychosom Med 2009; 71: 598606.
26Chen, PH, Chang, CK, Chiang, SJ, Lin, YK, Tsai, SY, Huang, SH. Diabetes mellitus and first episode mania associated with cardiovascular diseases in patients with older-age bipolar disorder. Psychiatry Res 2017; 249: 65–9.
27Ward, MC, White, DT, Druss, BG. A meta-review of lifestyle interventions for cardiovascular risk factors in the general medical population: lessons for individuals with serious mental illness. J Clin Psychiatry 2015; 76: e47786.
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Mood stabilisers and risk of stroke in bipolar disorder

  • Pao-Huan Chen (a1), Shang-Ying Tsai (a2), Chun-Hung Pan (a3), Chi-Kang Chang (a4), Sheng-Shiang Su (a5), Chiao-Chicy Chen (a6) and Chian-Jue Kuo (a7)...
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