Prevalence and Association of Lifestyle and Medical-, Psychiatric-, and Pain-related Comorbidities in Patients With Migraine

A Cross-sectional Study

Jiu-Haw Yin MD; Yu-Kai Lin MD; Chun-Pai Yang MD, PhD; Chih-Sung Liang MD; Jiunn-Tay Lee MD; Meei-Shyuan Lee PhD; Chia-Lin Tsai MD; Guan-Yu Lin MD; Tsung-Han Ho MD; Fu-Chi Yang MD, PhD


Headache. 2021;61(5):715-726. 

In This Article

Abstract and Introduction


Background and Objectives: Migraine has been associated with many comorbidities. However, lifestyle factors and the presence of comorbid diseases have not previously been extensively studied in the same sample. This study aimed to compare the prevalence of unhealthy lifestyle factors and comorbid diseases between patients with migraine and migraine-free controls with subgroup analyses to determine the pathophysiology and possible consequences.

Methods: This cross-sectional study recruited 1257 patients with migraine between the ages of 20 and 65 years from a headache outpatient clinic in Taiwan and 496 non-migraine controls. All participants completed questionnaires regarding demographics, migraine diagnosis, sleep, headache burden, and medical, pain, and psychiatric conditions. Participants also underwent a structured interview. The associations between comorbidities and migraine were investigated and further stratified by sex and aura.

Results: Patients with migraine with aura had an unhealthier lifestyle compared with controls in the form of current smoking status (15.5% [67/431] vs. 11.5% [57/496], p = 0.013). Furthermore, medical- (e.g., thyroid disease; 7.2% [91/1257 vs. 2.8% [14/496]; p = 0.006), psychiatric- (e.g., depression; 6% [76/1257 vs. 2.6% [13/496]; p = 0.031), and pain-related (e.g., fibromyalgia; 8% [101/1257 vs. 3.2% [16/496]; p = 0.006) comorbidities were more prevalent in patients compared with controls. Subgroup analyses revealed that chronic migraine, migraine with aura, and female sex were associated with a greater number of significant comorbidities than episodic migraine, migraine without aura, and male patients with migraine, respectively.

Conclusion: Individuals seeking treatment for migraine reported greater levels of smoking and medical, psychiatric, and pain conditions than non-treatment-seeking healthy controls who were recruited from the community. Understanding the relationship between migraine and comorbid diseases may improve medical care as well as the quality of life.


Migraine headaches are the second most common type of primary headache among adults, affecting approximately 18.9% of women and 9.8% of men globally.[1] According to the Global Burden of Disease study, migraine is the sixth most prevalent burdensome disease, and the second most common cause of years lived with disability in the world.[1] The disorder is characterized by recurrent attacks of moderate to severe throbbing or pulsing pain on one side of the head that can be aggravated by routine physical activity. Attacks can last 4–72 h (untreated or unsuccessfully treated) and are often accompanied by nausea and vomiting and sensitivity to light (photophobia) and sound (phonophobia).[2]

The term comorbidity refers to the presence of more than one disease/condition in the same person at a rate higher than expected by chance,[3] and the presence of a comorbidity increases the burden of migraine on the lives of affected individuals. Previous studies have shown that migraine is associated with many comorbidities including psychiatric disorders (e.g., depression, anxiety, adult attention deficit hyperactivity disorder, bipolar spectrum disorder, suicidal ideation, and attempts), sleep disorders (e.g., insomnia, restless legs syndrome, poor sleep quality, latency, and duration), pain disorders (e.g., fibromyalagia and dysmenorrhea), and a broad spectrum of somatic symptoms.[4–10] Furthermore, previous research has shown that certain unhealthy lifestyle factors may play an important role in triggering migraine headaches.[11] One of them, stress, was the primary trigger of migraine without aura, and common precipitants of migraine without aura were sleep deprivation, hunger, menses, fatigue, alcohol, sleep excess, and smoking.[11]

For a variety of reasons, it is important to understand the specific comorbidities in migraine. First, the recognition of migraine comorbidities may help to identify the genetic or biological mechanisms that promote the development of new therapies and facilitate disease management. Second, it can improve the prognosis. Studies have shown that patients with migraine with psychiatric comorbidities have poorer outcomes of migraine treatment and increased disability as compared to those with migraine headache alone.[9,12] Some lifestyle factors and comorbidities have also been confirmed as risk factors for developing chronic migraine or chronic daily headache,[13] and having multiple comorbidities in people with migraine is associated with medication adaptation headache, which significantly increases an individual's risk of developing chronic migraine.[14] A previous review revealed that sleep disturbance, higher headache day frequency, overuse of acute medications, and depression were the strongest risk factors for the new onset of chronic migraine.[13] In addition to disease progression, comorbidity may limit treatment options. For example, comorbid asthma in migraine may limit the ability to use β-blockers, and psychiatric comorbidity may limit the ability to use topiramate for migraine prevention.

Many studies have examined the relationship between migraine and single comorbidities.[5–8,10] To the best of our knowledge, lifestyle factors and migraine comorbidities have not previously been extensively studied in the same sample. The relationship between risk factors and certain subgroups of migraine (e.g., with or without aura, episodic or chronic), or personal characteristics (e.g., sex) remains uncertain. In our previous study, we found that a high frequency of migraine was associated with a higher suicide risk in patients with aura, but not in patients without aura. Additionally, subgroup analyses stratified by sex revealed that the associations of migraine frequency with suicide risk were observed only in female patients with aura.[6] We hypothesized that subjects with migraine with aura and chronic migraine, as well as female patients with migraine, would be more likely to have more comorbid diseases. Therefore, we aimed to compare the prevalence of unhealthy lifestyle factors and comorbidities in a large number of well-defined migraine subgroups and headache-free controls to discuss the pathophysiology and possible consequences.