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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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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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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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Response to article titled “Mood stabilizers and risk of stroke in bipolar disorder”

POOJA PATNAIK KUPPILI, SENIOR RESIDENT, AIIMS, JODHPUR
KARTIK SINGHAI, JUNIOR RESIDENT, AIIMS, JODHPUR
NARESH NEBHINANI, ASSOCIATE PROFESSOR, AIIMS, JODHPUR
18 December 2018

Dear sir

We read with great interest the article titled “Mood stabilizers and risk of stroke in bipolar disorder” by Chen et al., 2018 published in your esteemed journal. The authors have assessed the association between mood stabilizers and risk of stroke in patients suffering from bipolar disorder (BD). They have addressed multiple potential confounders such as age, gender, physical illness and concomitant medication. However, we would like to discuss some important factors which could have influenced the study findings

Firstly, the study did not consider the role of psychiatric comorbidity. Only admission for BD was taken into account. Certain psychiatric illnesses are common in patients suffering from BD and are noted to be risk factors for stroke as well. For example, the lifetime prevalence of anxiety disorder in BD was found to be 42.7%. 1Further, anxiety disorders have been associated with 24% increased risk of stroke compared to general population.2

Secondly, the role of psychosocial factors in stroke is not addressed. It is important to note that BD is associated with several psychosocial factors and a recent meta-analysis mentions that the risk of stroke is increased by psychological, vocational and interpersonal factors by almost 39%, 35% and 16% respectively.3

Thirdly, BD is associated with high rates of non adherence to medication. Since, the study focuses on the association between mood stabiliser and BD, the adherence to MS is an important variable to be considered. This point is worth highlighting as the mean prevalence of non-adherence to medication was found to range from 41.5% to 43%.4

Fourthly, the role of oral contraceptive pills has not been discussed. The increased risk of stroke with oral contraceptives is well known. About 42.7% of the sample consisted of women. Oral contraceptives are used commonly by women for contraception as well as prescribed for Poly Cystic Ovarian Syndrome, which is not uncommonly seen with use of Valproate.

Fifthly the comorbidity of seizure disorder has not been considered. This is important to address mainly for two reasons. Firstly, preparations of Valproate, Carbamazepine are prescribed in patients with seizure disorder or epilepsy as well as in patients with BD. Further, literature exists that late onset epilepsy has been associated with increased risk of stroke. 5 This is a point to be noted as almost 61% of the sample was recruited at age more than 45 years.

Lastly, the term “Any mood stabilizer” is not clearly defined. For example, the number of patients on any mood stabilizer during case period is 212. However, sum of patients as per numbers given separately for Carbamazepine (35), Valproic acid (118), Lithium (62) and Lamotrigine (18) is 233.

Declaration of interest: The authors declare no source of funding or conflict of interest

References:

1. Nabavi B, Mitchell AJ, Nutt D. A lifetime prevalence of comorbidity between bipolar affective disorder and anxiety disorders: a meta-analysis of 52 interview-based studies of psychiatric population. EBioMedicine. 2015;2(10):1405-19.

2. Perez-Pinar M, Ayerbe L, González E, Mathur R, Foguet-Boreu Q, Ayis S. Anxiety disorders and risk of stroke: a systematic review and meta-analysis. European Psychiatry. 2017; 41:102-8.

3. Lightbody CE, Clegg A, Patel K, Lucas JC, Storey H, Hackett ML, Watkins DC. Systematic Review and Meta-Analysis of Psychosocial Risk Factors for Stroke. InSeminars in neurology.2017; 37(3):294-306.

4. Chakrabarti S. Medication non-adherence in bipolar disorder: Review of rates, demographic and clinical predictors. World Journal of Meta-Analysis. 2017;5(4):103-23.

5. Ben‐Menachem E. Epilepsy as a warning sign for stroke. Epilepsy currents. 2005; 5(1):42-3.

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Conflict of interest: None declared

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