Panic Disorder and Migraine

Comorbidity, Mechanisms, and Clinical Implications

Todd A. Smitherman, PhD, FAHS; Elizabeth D. Kolivas, MA; Jennifer R. Bailey, MA


Headache. 2013;53(1):23-45. 

In This Article

Abstract and Introduction


A growing body of literature suggests that comorbid anxiety disorders are more common and more prognostically relevant among migraine sufferers than comorbid depression. Panic disorder (PD) appears to be more strongly associated with migraine than most other anxiety disorders. PD and migraine are both chronic diseases with episodic manifestations, involving significant functional impairment and shared symptoms during attacks, interictal anxiety concerning future attacks, and an absence of identifiable secondary pathology. A meta-analysis of high-quality epidemiologic study data from 1990 to 2012 indicates that the odds of PD are 3.76 times greater among individuals with migraine than those without. This association remains significant even after controlling for demographic variables and comorbid depression. Other less-rigorous community and clinical studies confirm these findings. The highest rates of PD are found among migraine with aura patients and those presenting to specialty clinics. Presence of PD is associated with greater negative impact of migraine, including more frequent attacks, increased disability, and risk for chronification and medication overuse. The mechanisms underlying this common comorbidity are poorly understood, but both pathophysiological (eg, serotonergic dysfunction, hormonal influences, dysregulation of the hypothalamic–pituitary–adrenal axis) and psychological (eg, interoceptive conditioning, fear of pain, anxiety sensitivity, avoidance behavior) factors are implicated. Means of assessing comorbid PD among treatment-seeking migraineurs are reviewed, including verbal screening for core PD symptoms, ruling out medical conditions with panic-like features, and administering validated self-report measures. Finally, evidence-based strategies for both pharmacologic and behavioral management are outlined. The first-line migraine prophylactics are not indicated for PD, and the selective serotonin re-uptake inhibitors used to treat PD are not efficacious for migraine; thus, separate agents are often required to address each condition. Core components of behavioral treatments for PD are reviewed, and their integration into clinical headache practice is discussed.


Migraine affects 12% of the population annually[1] (37 million Americans), contributing to high medical costs,[2] reduced quality of life,[3] and significant functional impairment.[3,4] Due to its high prevalence and negative impact, the World Health Organization ranks migraine among the top 20 causes of disability worldwide (number 12 among women specifically).[5] The personal and societal burden of migraine is compounded by the presence of other commonly co-occurring disorders, including cardiovascular disorders (particularly among migraineurs with aura: coronary heart disease, stroke, patent foramen ovale), obesity, epilepsy, other chronic pain conditions, and psychiatric disorders.[6–8] Among these, psychiatric disorders are of particular interest because of their high prevalence and recognition as modifiable risk factors for migraine progression.[9,10]

Although a large proportion of individuals with headache do not meet diagnostic criteria for comorbid psychiatric diagnoses, the lifetime prevalence of mood and anxiety disorders is significantly higher among individuals with migraine than the general population.[11–13] Considerable evidence confirms a significant relationship between depression and migraine, such that migraine portends a two- to fourfold increased odds for depression,[11–14] that this relationship is bidirectional in nature and unique to migraine headache,[15,16] and that comorbid depression is associated with lower quality of life than migraine alone.[17] Compared with depression, however, the relationship between anxiety disorders and migraine is often overlooked.[18] Comorbidity studies on depression and migraine outnumber those on anxiety and migraine by a ratio of 2:1,[19] even though anxiety disorders are the most prevalent class of psychiatric disorder in the general population (28% lifetime prevalence).[20]

The majority (51–58%) of migraineurs will meet criteria for at least one anxiety disorder during their lifetime, and multiple epidemiologic studies indicate that anxiety disorders are nearly twice as common among migraineurs as is depression.[11,21,22] Indeed, a large-scale French study of 1957 migraine sufferers found that significant depressive symptomatology rarely occurs alone and is almost always comorbid with anxiety (3.5% with depression alone vs 28% with anxiety alone, and 19% with both depression and anxiety).[23] Further, a growing number of studies suggest that anxiety disorders confer greater negative impact among migraineurs than depression, such that only anxiety predicts long-term migraine persistence, headache-related disability, and reduced perceptions of efficacy and satisfaction with acute migraine treatment.[23,24] Collectively, these findings support an argument that anxiety disorders should merit frequent attention among headache researchers and practitioners. This argument is bolstered by findings within the broader chronic pain literature indicating that anxiety disorders are more strongly associated with various chronic pain conditions than depression.[25,26]