Although the underlying cause of migraine remains unknown, the condition has been associated with genetic, hormonal, environmental, dietary, and psychological factors. Chronic migraine is also often linked with psychiatric disorders, including generalized anxiety disorder, “characterized by emotionally unpleasant developmentally inappropriate states of unfocused uneasiness and worry, usually about objectively unthreatening situations,” the authors wrote.
One study on a Canadian population found generalized anxiety disorder was 2.5 times more prevalent in migraineurs than those without migraine. Furthermore, “prolonged anxiety has been proposed as a causal factor influencing the role of neuropathologic processes and leading to increased risk of other psychiatric disorders, as well as the transformation of episodic migraines into chronic events.”
To systematically evaluate the connection between anxiety and migraine, and to determine whether the comorbidity of migraine with anxiety is higher in migraineurs vs non-migraineurs, the investigators searched electronic databases Medline, PsycINFO, EMBASE (Ovid), Science Direct (Elsevier), Cochrane, and PubMed for studies on both conditions.
Of the initial 2132 citations collected, 8 studies (conducted in Canada, Turkey, Brazil, the United States, New Zealand, Korea, China and the European Union) were included in the systematic review. In the majority of studies, migraine was diagnosed using International Classification of Headache Disorders, while the Goldberg Anxiety Disorder; Depression, Anxiety and Stress Score DASS-21; Goldberg Anxiety Scale; Hamilton Anxiety Scale; and self-reported anxious symptomology were used to screen for anxiety.
“In all the studies, the results demonstrated a strong relationship in terms of odds ratios (ORs) between anxiety and migraine compared to non-migraineurs,” the authors wrote. “Both the Brazilian studies showed exceptionally high ORs (OR = 13 and 25 in order), with the other 6 studies showing ORs ranging from 1.77 to 4.5.”
Additional findings included:
- An average OR of 2.33 (95% CI, 2.20-2.47) for prevalence and cross-sectional studies of anxiety comorbidity among migraineurs compared with non-migraineurs or healthy participants
- For prevalence studies, the OR was 2.54 (95% CI, 1.48-4.35)
- The average OR for cross-sectional studies was higher at 8.14 (95% CI, 0.99-66.83) (high ORs and CIs for this group were due to inclusion of the 2 Brazilian studies with very high ORs)
- For the 2 cohort studies an average risk ratio of 1.63 (95% CI, 1.37-1.93) was reported
“Clearly migraine and anxiety are comorbid, and the incidence of occurrence is almost 4 times higher compared to non-migraineurs,” the researchers wrote. Their results underscore the need for concurrent assessment of migraineurs for neurological symptoms of migraine and psychiatric symptoms associated with anxiety or depression.
In order to better understand migraine’s etiology, the investigators suggest future studies seek more information regarding the onset of biological symptoms associating migraine with physiological measures of anxiety as currently, “there is little biological information regarding the onset of clinical anxiety with regard to the onset of the migrainous events or vice versa.” Future investigations should also research the comorbidity’s prevalence among migraineurs with aura specifically.
When migraineurs present with the comorbidity, treatment options that lead to improvements for both conditions should be explored, as the symptoms appear to be an outcome of sensorimotor, interoceptive, and cognitive adaptations, they added.
The small number of studies included in the review in addition to the observational nature of studies mark limitations.
However, “The comorbidity of migraine and anxiety is strong and significant and the comorbidity of anxiety with migraine is significantly higher among migraineurs vs non-migraineurs,” the authors concluded.
Karimi L, Wijeratne T, Crewther SG, Evans AE, Ebaid D, Khalil H. The migraine-anxiety comorbidity among migraineurs: a systematic review. Front Neurol. Published online January 18, 2021. doi:10.3389/fneur.2020.613372