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Psychiatric Comorbidity and Migraine

Guest Editor: Todd A. Smitherman, Ph.D.

Dr. Smitherman is Assistant Professor in the Department of Psychology at the University of Mississippi. His research focuses on psychiatric comorbidities in migraine and other behavioral issues in headache management.

 Psychiatric Comorbidity and Migraine

The relationship between migraine and psychiatric disorders remains of growing interest to headache researchers and clinicians alike. Headache has been at the forefront of many publications on this topic, and as recently as 2006 sponsored a special issue and special series devoted to research on psychiatric comorbidities. The present issue briefly summarizes and provides links to relevant articles published in Headache.

Epidemiologic and Clinical Studies
Although many headache patients will not suffer from clinically significant psychopathology, a large body of literature confirms that patients with migraine are significantly more likely to suffer from a psychiatric disorder than are those without headache. Though variability exists among studies regarding prevalence rates, most indicate that migraineurs are 2 to 5 times more likely to be diagnosed with a depressive or anxiety disorder, even after controlling for age and gender.1-6 Comorbid psychiatric disorders are most prevalent among migraine patients presenting to clinical settings and those with chronic (versus episodic) migraine. Major depression and bipolar disorder are the most commonly-studied mood disorders, and the anxiety disorders studied most frequently are panic disorder, generalized anxiety disorder, and phobias.

Longitudinal studies indicate that the relationship between depression and migraine is bidirectional, such that some patients develop depression subsequent to migraine and others have a history of depression prior to migraine onset.7 Though limited by comparison, longitudinal studies of anxiety disorders also suggest a bidirectional relationship. In some patients anxiety precedes migraine, which in turn is followed by depression. Psychiatric comorbidity among children and adolescents is also a well-recognized phenomenon,8-11 though this body of literature is far smaller than that on adults.
Most research on psychiatric comorbidities has focused on depression, despite data that anxiety disorders remain the most prevalent class of psychiatric disorder in the general population, are almost twice as common in migraineurs, and likely portend a greater prognostic challenge. Other Axis I psychiatric disorders have been studied less frequently. Studies assessing substance use have obtained mixed results, with some finding higher rates of abuse/dependence among migraineurs and others finding no differences between groups. Consistently, though, psychiatric comorbidity is associated with medication overuse.12 A newer and growing body of literature attests to the connection between posttraumatic stress disorder and migraine.13-15
Axis II personality disorders are studied more infrequently by comparison, but occur in 26% of chronic headache inpatients.16  Borderline personality disorder has been described most frequently in the empirical literature,17,18 but epidemiologic and further clinic-based studies are needed to better understand the relationship of various personality disorders to migraine.

Impact of Psychiatric Comorbidities
Psychiatric comorbidities do not occur in a vacuum; instead they negatively impact patient quality of life and headache management. Comorbid depression and anxiety disorders are associated with reduced quality of life, poorer long-term outcomes and response to headache treatments, and increased risk of medication overuse.19,20 In terms of costs, migraineurs with comorbid depression or anxiety accrue nearly $5,000 more in medical expenses each year than do migraine patients without depression or anxiety.21  Even otherwise healthy college students with infrequent migraines (<1 per week) evidence more symptoms of depression and anxiety, report reduced quality of life, and miss more days of school than do students without migraine.22
Importantly, psychiatric disorders are now identified as factors influencing the progression of migraine from episodic into chronic forms (“chronification”).23 Because they are amenable to treatment and thus can potentially reduce chronification, treatment studies focusing on these comorbidities are sorely needed.

The high co-occurrence of psychiatric disorders and migraine, as well as their bidirectional relationship, suggests that these disorders likely are comorbid because they share pathophysiologic mechanisms. Potential mechanisms include dysfunctions in central serotonergic availability, fluctuations in ovarian hormone levels (for women), dysregulation of the hypothalamic-pituitary adrenal (HPA), and sensitization of both sensory and affective neural networks. Depression and anxiety also appear important in the connection between obesity and migraine.24  Recent twin studies attempting to model the genetic architecture of these comorbidities suggest that a significant proportion of their variance is due to shared genetic influences.25,26

Clinical Implications: Assessment and Treatment
The present state-of-affairs is such that epidemiologic and basic science research is only beginning to be applied to clinical settings. No studies exist that assess the effects of treating psychiatric comorbidity on migraine symptoms, and clinical trials of pharmacologic migraine interventions typically exclude individuals with significant depression or anxiety. Drug studies that have included depressed patients have produced mixed results as to whether headache agents favorably impact depression or whether concurrent depression predicts response to treatment. As a result, implications for treatment are largely based on clinical experience and extrapolations from related literatures.27
The high rates of comorbidity between migraine and psychiatric disorders suggest that all migraine patients should be screened for depression and anxiety at a minimum. This may range from brief verbal screening about core symptoms in the infrequent migraineur to more formal questionnaire and/or interview assessment in a chronic migraine patient or a patient presenting to a specialty clinic. Assessment should focus primarily on cognitive and emotional symptoms, as transdiagnostic physical symptoms often obscure accurate psychiatric diagnosis.28  Patients with high levels of depression and anxiety should also be assessed for medication overuse. Recommended assessment strategies are provided in Maizels et al.29
Regarding treatment, pharmacologic interventions (eg, antidepressants, anticonvulsants) that simultaneously treat both migraine and the psychiatric disorder offer some promise, but they are often better in theory than practice due to differential dosing requirements and resulting side effect profiles.30-32 Treating the comorbid psychiatric disorder may thus require use of a separate agent and/or behavioral interventions including cognitive-behavioral therapy (CBT). Individual CBT techniques may be adapted within the context of physician practice settings and include activity scheduling, relaxation training, and exposure exercises. These approaches may be combined with a standard pharmacologic or behavioral regimen specific to headache and are described in more detail in the accompanying articles.33-35

The subsequent decades of research on this topic offer promise for better understanding the underlying mechanisms and clinical implications. Future studies should focus on studying these topics using precise diagnostic criteria, differentiating clinical from subclinical psychiatric symptomatology, investigating psychiatric disorders as moderator and mediator variables, and developing treatment algorithms that are specific to particular psychiatric disorders.5 Ultimately, however, whether treating depression or anxiety improves headache symptoms is unknown and should become a priority of future research.


Empirical Associations between Psychopathology and Migraine
1. Breslau N, Andreski P. Migraine, personality, and psychiatric comorbidity. Headache. 1995;35:382-386.
2. Hamelsky SW, Lipton RB. Psychiatric comorbidity of migraine. Headache. 2006;46:1327- 1333.
3. Jette N, Patten S, Williams J, Becker W, Wiebe S. Comorbidity of migraine and psychiatric disorders—A national population-based study. Headache. 2008;48:501-516.
4. Juang KD, Wang SJ, Fuh JL, Lu SR, Su TP. Comorbidity of depressive and anxiety disorders in chronic daily headache and its subtypes. Headache. 2000;40:818-823.
5. Lake AE III, Rains JC, Penzien DB, Lipchik GL. Headache and psychiatric comorbidity: Historical context, clinical implications, and research relevance. Headache. 2005;45:493-506.
6. Merikangas KR, Stevens DE, Angst J. Psychopathology and headache syndromes in the community. Headache. 1994;34:S17-S22.
7. Breslau N, Davis GG, Schultz LR, Paterson EL. Migraine and major depression: A longitudinal study. Headache. 1994;34:387-393.
8. Cunningham SJ, McGrath PJ, Ferguson HB, et al. Personality and behavioural characteristics in pediatric migraine. Headache. 1987;27:16-20.
9. Kaiser RS. Depression in adolescent headache patients. Headache. 1992;32:340-344.
10. Pakalnis A, Gibson J, Colvin A. Comorbidity of psychiatric and behavioral disorders in pediatric migraine. Headache. 2005;45:590-596.
11. Powers SW, Kruglak Gilman D, Hershey A. Headache and psychological functioning in children and adolescents. Headache. 2006;46:1404-1415.
12. Radat F, Sakh D, Lutz G, El Amrani M, Ferreri M, Bousser MG. Psychiatric comorbidity is related to headache induced by chronic substance use in migraineurs. Headache.1999; 39:477–80.
13. de Leeuw R, Schmidt JE, Carlson CR. Traumatic stressors and post-traumatic stress disorder symptoms in headache patients. Headache. 2005;45:1365-1374.
14. Peterlin BL, Tietjen GE, Brandes JL, et al. Posttraumatic stress disorder in migraine. Headache. 2009;49:541-551.
15. Peterlin BL, Tietjen G, Meng S, Likicker J, Bigal M. Post-traumatic stress disorder in episodic and chronic migraine. Headache. 2008;48:517-522.
16. Lake AE III, Saper JR, Hamel RL. Comprehensive inpatient treatment of refractory chronic daily headache. Headache. 2009;49:555-562.
17. Rothrock J, Lopez I, Zweilfer R, et al. Borderline personality disorder and migraine. Headache. 2007;47:22-26.
18. Saper JR, Lake AE III. Borderline personality disorder and the chronic headache patient: Review and management recommendations. Headache. 2002;42:663-674.

Impact of Psychiatric Comorbidities

19. Fichtel A, Larsson B. Psychosocial impact of headache and comorbidity with other pains among Swedish school adolescents. Headache. 2002;42:766-775.
20. Lake AE III. Medication overuse headache: biobehavioral issues and solutions. Headache. 2006;46 (Suppl. 3):S88-S97.
21. Pesa J, Lage MJ. The medical costs of migraine and comorbid anxiety and depression. Headache. 2004;44:562-570.
22. Smitherman TA, McDermott MJ, Buchanan EM. Negative impact of episodic migraine on a university population: Quality of life, functional impairment, and comorbid psychiatric symptoms. Headache. In press.
23. Bigal ME, Lipton RB. Modifiable risk factors for migraine progression. Headache. 2006;46:1334-1343.

24. Tietjen GE, Peterlin BL, Brandes JL, et al. Depression and anxiety: effect on the migraine-obesity relationship. Headache. 2007;47:866-875.
25. Schur EA, Noonan C, Buchwald D, Goldberg J, Afari N. A twin study of depression and migraine: evidence for a shared genetic vulnerability. Headache. 2009;49:1493-1502.
26. Ligthart L, Nyholt DR, Penninx BW, Boomsma DI. The shared genetics of migraine and anxious depression. Headache. 2010;50:1549-1560.

Implications for Assessment and Treatment
27. Baskin SM, Lipchik GL, Smitherman TA. Mood and anxiety disorders in chronic headache. Headache. 2006;46(Suppl. 3):S76-S87.
28. Holm JE, Penzien DB, Holroyd KA, Brown TA. Headache and depression: confounding effects of transdiagnostic symptoms. Headache. 1994;34:418-423.
29. Maizels M, Smitherman TA, Penzien DB. A review of screening tools for psychiatric comorbidity in headache patients. Headache. 2006;46(Suppl. 3):S98-S109.
30. Griffith JL, Razavi M. Pharmacological management of mood and anxiety disorders in headache patients. Headache. 2006;46(Suppl. 3):S133-S141.
31. Sheftell FD, Atlas SJ. Migraine and psychiatric comorbidity: from theory and hypotheses to clinical application. Headache. 2002;42:934-944.
32. Silberstein SD, Dodick D, Freitag F, et al. Pharmacological approaches to managing migraine and associated comorbidities—clinical considerations for monotherapy versus polytherapy. Headache. 2007;47:585-599.
33. Lipchik GL, Smitherman TA, Penzien DB, Holroyd KA. Basic principles and techniques of cognitive-behavioral therapies for comorbid psychiatric symptoms among headache patients. Headache. 2006;46(Suppl. 3):S119-S132.
34. Powers SW, Kruglak Gilman D, Hershey AD. Suggestions for a biopsychosocial approach to treating children and adolescents who present with headache. Headache. 2006;46(Suppl. 3):S149-S150.
35. Smitherman TA, Maizels M, Penzien DB. Headache chronification: Screening and behavioral management of comorbid depressive and anxiety disorders. Headache. 2008;48:45-50.

Virtual Issue compiled online 26 January 2011 

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