|Year : 2019 | Volume
| Issue : 4 | Page : 192-197
Risk of developing migraine among patients with posttraumatic stress disorder: A nationwide longitudinal study
Mao-Hsuan Huang M.D 1, Yee-Lam E Chan M.D 1, Ju-Wei Hsu M.D 2, Ya-Mei Bai M.D., Ph.D 2, Kai-Lin Huang M.D 2, Shih-Jen Tsai M.D 2, Tung-Ping Su M.D 3, Cheng-Ta Li M.D., Ph.D 2, Wei-Chen Lin M.D 2, Tzeng-Ji Chen M.D., P.D 4, Mu-Hong Chen M.D., Ph.D 2
1 Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan
2 Department of Psychiatry, Taipei Veterans General Hospital; Department of Psychiatry, College of Medicine, National Yang-Ming University, Taipei, Taiwan
3 Department of Psychiatry, Taipei Veterans General Hospital; Department of Psychiatry, College of Medicine, National Yang-Ming University; Department of Psychiatry, Cheng Hsin General Hospital, Taipei, Taiwan
4 Department of Family Medicine, Taipei Veterans General Hospital; Institute of Hospital and Health Care Administration, National Yang-Ming University, Taipei, Taiwan
|Date of Submission||28-Jun-2019|
|Date of Decision||30-Jul-2019|
|Date of Acceptance||30-Jul-2019|
|Date of Web Publication||23-Dec-2019|
No. 201, Shih-Pai Road, Section 2, Taipei 112
Source of Support: None, Conflict of Interest: None
Objective: We intended to investigate the risk of developing migraine among patients with posttraumatic stress disorder (PTSD). Methods: With the Taiwan's National Health Insurance Research Database, we examined 5,644 patients with PTSD and 22,576 age- and sex-matched controls between 2002 and 2009 and followed them to the end of 2011. Individuals who developed migraine during the follow-up period were identified. Results: Patients with PTSD had a significantly higher incidence of developing migraine (5.74 vs. 1.22 per 1,000 person-years, p < 0.001) during the follow-up period than the controls. We did Cox regression analysis with adjustments of demographic data and medical comorbidities and found that patients with PTSD were more likely to develop migraine (hazard ratio [HR] = 3.83, 95% confidence interval [CI] = 2.82–5.20) than the control group. Sensitivity analyses after excluding the 1st year (HR = 2.89; 95% CI = 2.04–4.08) or the first 3 years (HR = 2.07; 95% CI = 1.32–3.24) of observation showed consistent findings. Moreover, a high frequency of psychiatric clinics visiting for PTSD was associated with an increased risk of developing migraine. Conclusion: Patients with PTSD had a higher risk of migraine than the controls. The symptom severity of PTSD may be associated with an increased risk of migraine. Further studies are required to investigate the underlying pathophysiology between PTSD and migraine.
Keywords: comorbidities, headache, survival curve, Taiwan's National Health Insurance Research Database
|How to cite this article:|
Huang MH, Chan YLE, Hsu JW, Bai YM, Huang KL, Tsai SJ, Su TP, Li CT, Lin WC, Chen TJ, Chen MH. Risk of developing migraine among patients with posttraumatic stress disorder: A nationwide longitudinal study. Taiwan J Psychiatry 2019;33:192-7
|How to cite this URL:|
Huang MH, Chan YLE, Hsu JW, Bai YM, Huang KL, Tsai SJ, Su TP, Li CT, Lin WC, Chen TJ, Chen MH. Risk of developing migraine among patients with posttraumatic stress disorder: A nationwide longitudinal study. Taiwan J Psychiatry [serial online] 2019 [cited 2020 Apr 7];33:192-7. Available from: http://www.e-tjp.org/text.asp?2019/33/4/192/273861
| Introduction|| |
Migraine is a common and often disabling neurovascular condition characterized by moderate-to-severe recurrent headaches . It has been associated with various medical conditions , and it is ranked as the seventh leading cause of disability worldwide when combined with anxiety and depression .
Patients with psychiatric disorders, such as major depression, anxiety, panic disorder, and bipolar disorder, are commonly found to be comorbid with migraine ,. Several studies have examined the rôle of posttraumatic stress disorder (PTSD), a severe mental disorder resulting from a life-threatening trauma, on subsequent migraine occurrence. Increased evidence has indicated an association between PTSD and migraine ,,. Researchers reported that PTSD is more common in adults with migraine than the nonmigraine controls . Peterlin et al. found that the 12-month prevalence of PTSD is 14.3% in patients with migraine as compared with 2.1% of those without any headache . Differences in the study methodology and data sources, as well as the small sample sizes of the previous studies, have caused uncertainty around the actual risk of migraine among patients with PTSD.
With the Taiwan's National Health Insurance Research Database (NHIRD), a large sample size, with a longitudinal study design, we intended to investigate the temporal association of PTSD with subsequent migraine risk in this study. We hypothesized that patients with PTSD would be more likely to develop migraine later in life compared with those the non-PTSD control group. Furthermore, we hypothesized that the higher clinical severity of PTSD might be related to the greater risk of migraine occurrence.
| Methods|| |
Taiwan's National Health Insurance is a mandatory universal health insurance program that was inaugurated in 1995 and covers up to 99% of the country's 23 million residents (www.nhi.gov.tw/). The National Health Research Institute (NHIRD provides comprehensive patient information, such as demographic data, clinical visit dates, and disease diagnoses. All identities are encrypted to ensure patients' privacy. The diagnostic codes used are based on the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). The NHIRD has been used extensively in numerous epidemiologic studies in Taiwan ,,,,.
Inclusion criteria for patients with posttraumatic stress disorder and the control group
Patients who were diagnosed with PTSD (ICD-9-CM code: 309.81) by board-certified psychiatrists between January 1, 2002, and December 31, 2009, and who had no history of migraine (ICD-9-CM code: 346) before enrollment were included as the PTSD cohort. The time of PTSD diagnosis was defined as the time of enrollment. The age-, sex-, and time of enrollment-matched (1: 4) control cohort was randomly identified after eliminating the study participants, those who had been given a diagnosis of PTSD at any time, and those with migraine before enrollment. Cases of migraine diagnosed by board-certified neurologists, pediatricians, or pain specialists were identified during the follow-up period and followed until December 31, 2011, or the date of death. Medical and psychiatric comorbidities were assessed as confounding factors; those included depressive disorder, hypertension, dyslipidemia, diabetes mellitus, cerebrovascular diseases, epilepsy, meningitis and encephalitis, and head injury. Furthermore, the frequency of psychiatric clinical visits for PTSD (times per year) was assessed and regarded as the disease severity of PTSD in our study. All diagnoses were given at least twice by physicians to achieve diagnostic validity. The level of urbanization (level 1 to level 5; level 1, most urbanized region; level 5, least urbanized region) was also assessed .
This study was approved by the institutional review board of Taipei Veterans General Hospital without requirement of obtaining informed consent from the study participants (protocol number = 2018-07-016AC, approval date = July 20, 2018).
For between-group comparisons, the independent t-test was used for continuous variables and Pearson's Chi-square test was used for categorical variables, where appropriate. We tested survival probability with log-rank test. The Cox regression model was used to investigate the hazard ratios (HRs) with 95% confidence intervals (CIs) of developing migraine between patients with PTSD and the control group after adjustment for demographic data (age, sex, level of urbanization, and income) and medical and psychiatric comorbidities (depressive disorder, hypertension, dyslipidemia, diabetes mellitus, cerebrovascular diseases, head injury, epilepsy, meningitis, and encephalitis). We did sensitivity tests to validate the findings after excluding our observations on the first year and the first three years. We did subanalyses of the risk of migraine with PTSD stratified by age groups: children (< 18 years), adults (18–64 years), and the elderly (≥ 65 years). We also investigated the disease severity of PTSD indicated by the frequency of psychiatric clinical visits for PTSD and the risk of subsequent migraine.
All data processing and statistical analyses were done using the Statistical Package for the Social Science software version 17 for Windows (SPSS Inc., Chicago, Illinois, USA) and Statistical Analysis System version 9.1 (SAS Institute, Cary, North Carolina, USA). The differences between the groups were considered significant if p < 0.05.
| Results|| |
We enrolled 5,644 patients with PTSD and 22,576 age- and sex-matched controls in our study. The study participants had an average age of 34.45 ± 15.26 years. The patients with PTSD had a significantly higher incidence of developing migraine (5.74 vs. 1.22 per 1,000 person-years, p< 0.001) and a shorter duration from enrollment to the diagnosis time of migraine than the control group [Table 1]. The prevalence of depressive disorder, hypertension, dyslipidemia, diabetes, cerebrovascular diseases, head injury, and epilepsy was higher among patients with PTSD compared with the controls [Table 1]. In addition, patients with PTSD had lower income than the controls [Table 1].
|Table 1. Demographic data and incidence of migraine of patients with posttraumatic stress disorder and the control group|
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The Kaplan–Meier survival curve with log-rank test showed that patients with PTSD had a significantly higher risk of developing migraine (p< 0.001) than the control group [Figure 1]. Cox regression analyses with the adjustments of demographic data and medical and psychiatric comorbidities showed that the patients with PTSD were more likely to develop migraine during the follow-up period than the control group. The risks were higher than the controls across all age groups (adolescents: HR = 4.59, 95% CI = 1.89–11.15; adults: HR = 3.75, 95% CI = 2.68–5.24; and the elderly: HR = 9.38, 95% CI = 1.74–50.67) [Table 2]. In addition, PTSD patients who were comorbid with cerebrovascular diseases, meningitis, and encephalitis exhibited higher risks of migraine [Table 2]. Furthermore, patients with a higher frequency of psychiatric clinical visits for PTSD had a greater risk of developing migraine later in life in a dose-dependent manner compared with the controls [Table 3].
|Figure 1. Survival curve of developing migraine among patients with PTSD and the control group. p < 0.001 using log-rank test. Solid line represents the control group; dot line represents patients with PTSD. PTSD, posttraumatic stress disorder.|
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|Table 2. Risk of developing migraine of patients with posttraumatic stress disorder and the control group§|
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|Table 3. Posttraumatic stress disorder severity and risk of developing migraine§|
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Sensitivity analyses after excluding the first year (HR = 2.89, 95% CI = 2.04–4.08) or the first three years (HR = 2.07, 95% CI = 1.32–3.24) of observation period showed consistent findings: patients with PTSD were associated with an elevated risk of subsequently developing migraine [Table 4].
|Table 4. Sensitivity test for the risk of developing migraine of patients with posttraumatic stress disorder and the control group§|
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| Discussion|| |
Our results supported the study hypotheses that patients with PTSD had an increased risk of developing migraine later in life than the non-PTSD controls [Table 1]. The significance of increased risk of migraine with PTSD was shown across all age groups [Table 2]. In addition, the higher clinical severity of PTSD was associated with the greater risk of subsequent migraine in a dose-dependent manner.
A growing body of evidence indicated a relationship between stressful life event and migraine, suggesting that stress aggravates or triggers the development of migraine . Tietjen et al. reported that patients with migraine are more likely to experience the lifetime physical or sexual abuse than the nonmigraine controls ,. In a population-based study of more than 5,000 participants, Peterlin et al. demonstrated that about 70% of patients who had the dual diagnoses of migraine and PTSD have reported PTSD-related symptoms occurred before the onset of headache . They further suggested that PTSD is associated with an increased predisposition to the development of migraine . In addition, a cross-sectional study that compared patients with and without migraine showed that PTSD (odds ratio = 2.3, 95% CI = 1.56–3.39) is a predictor of migraine . In accordance with their findings, our study result showed a higher migraine risk among patients with PTSD than the non-PTSD controls [Figure 1].
While previous research supported that psychiatric comorbidities increase the disability and burden associated with migraine , we found that PTSD patients with cerebrovascular diseases, meningitis, and encephalitis had the higher migraine risk compared to those without comorbidities. In addition, the association between the PTSD severity and migraine risk has rarely been discussed. Previous evidence reported that the cumulative effect of trauma exposure increases the risk of PTSD and other psychiatric disorders among patients with migraine ,. Smitherman et al. revealed that PTSD symptom severity is a predictor of migraine, the frequency of trauma exposure has also been found to be a predictor of migraine, but its effect is rather modest . Being compatible with the findings from previous studies, we defined the PTSD symptom severity in this study as the frequency of psychiatric clinical visits per year, and we correlated the risk of subsequent migraine with higher PTSD severity [Table 3].
The pathophysiology of PTSD increasing the migraine risk remains unknown. Several possibilities for the presence of psychiatric comorbidities with migraine have been postulated. Psychiatric factors are rare causes of headaches, and severe migraines can conversely give rise to various psychiatric dysfunctions . The most unifying theory is that the two disorders may share a common pathophysiological pathway that can lead to both conditions. Numerous possible mechanisms contribute to the PTSD–migraine association, including dysfunction of the autonomic system, hypothalamic–pituitary–adrenal axis, and serotonin modulation ,. Patients with PTSD have been shown to have lower serum levels of cortisol compared to those in healthy controls . Another study found that patients with migraine have a decreased serum cortisol level in response to cognitive stress . In addition, autonomic system dysfunction and low levels of brain serotonin have been demonstrated in both patients with PTSD and those with migraine ,,.
The strengths of our study are the large, well-defined sample of patients and the longitudinal study design. Our study provided evidence for the association between preceding PTSD and subsequent migraine. PTSD has been shown to worsen chronicity among patients with chronic pain, while the treatment of PTSD has been shown to lessen both pain and disability . There is a need for those who treat PTSD patients to be aware of the comorbidity with migraine, as these patients may be prone to financial, health, and interpersonal disease burdens . In addition, longitudinal studies are needed to test the hypothesis that PTSD might be a risk factor for migraine chronification. Moreover, our data revealed that patients with PTSD across all age groups had an increased risk of migraine. While few studies have discussed the association between the age of onset for PTSD and subsequent medical morbidity, our finding should motivate studies on the disease burden not only in adult patients but also in adolescents, and additional experiments are required to obtain a deeper understanding of the mechanisms involved in the pathogenesis of PTSD and migraine.
The readers are warned against overinterpreting the study results because this study has four limitations:
- The diagnosis of migraine and PTSD in the NHIRD was made by different physicians without standardized diagnostic assessments. In addition, only those who sought medical help for the diagnosis and treatment of neuropsychiatric illnesses were identified. The identification of patients may therefore be biased. But the patients with migraine identified in our study were diagnosed by board-certified neurologists, pediatricians, or pain specialists, yielding an improved diagnostic validity. Furthermore, we used a sensitivity test to reconfirm this association between PTSD and the risk of migraine. A higher HR of 2.89 and 2.07 still indicated significance, even after excluding the first 1-year and first 3-year observations [Table 4].
- The NHIRD did not provide information on family history and environmental factors. Inheritance has been recognized to play an important rôle in the etiology of migraine , and inheritance was estimated to account for 40% to 50% of an individual's susceptibility to migraine . In addition, patients with migraine commonly report that certain external factors such as meteorological changes can aggravate migraine attack . But some studies have shown conflicting results , which highlight the need to investigate the link between environmental factors and migraine. Furthermore, the NHIRD did not provide information on the type of traumatic events and at what age the traumatic life stressors occurred. This may be important as individuals who report adverse childhood experiences had been shown to be at an increased risk of chronic pain as adults .
- The symptom severity of PTSD may be biased by the definition of the frequency of psychiatric clinical visits because patients with PTSD without clinical visits may be misclassified. More investigations for the association between the PTSD symptom severity and an increased predisposition to migraine are needed.
- Our study findings did not reach a cause-and-effect association between headaches and PTSD. Further studies are needed to clarify the causal relationship between migraine and PTSD.
Our population-based longitudinal study found that patients with PTSD had a higher risk of migraine than the controls. The symptom severity of PTSD may be associated with an increased risk of migraine. Further studies are required to investigate the underlying pathophysiology between PTSD and migraine.
| Acknowledgment|| |
The authors thank Emily Ting for English editing.
| Financial Support and Sponsorship|| |
The study was supported by a grant from Taipei Veterans General Hospital (V103E10-001, V104E10-002, V105E10-001-MY2-1, V105A-049, V106B-020, V107B-010, and V107C-181) and Ministry of Science and Technology, Taiwan (107-2314-B-075-063-MY3 and 108-2314-B-075-037). The funding source had no rôle in any process of our study.
| Conflicts of Interest|| |
All authors report no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4]