Impact of psychiatric comorbidities
Psychiatric comorbidities are relevant clinically because they negatively impact the patient and complicate clinical decision making. Com-pared with migraineurs without a comorbid disorder, those with psychiatric comorbidity incur $5000 to $7800 more in yearly medical expenses, experience greater headache-related disability pertaining to daily role functioning, and have poorer quality-of-life and coping skills.11-13 In many cases, the comorbid disorder perpetuates a preoccupation with somatic sensations and fear of pain, in turn fostering avoidance of situations and behaviors that are actually unrelated to migraine.
Clinicians often expect the presence of psychiatric comorbidity to portend a poorer migraine prognosis. Clinical studies that have examined psychiatric comorbidities as prognostic factors are few and their findings are somewhat mixed. Nevertheless, most researchers and clinicians continue to maintain that psychiatric comorbidities likely will interfere with headache treatment outcomes under a variety of circumstances.
Particularly compelling evidence is provided by a longitudinal study that found the presence of psychiatric disorders (particularly multiple diagnoses) to be predictive of poor headache outcomes.14 Results demonstrated that 86% of headache sufferers who had 2 or more comorbid psychiatric disorders either had no improvement or had deterioration in their headache condition. Similarly, 62% with a single comorbid condition remained unchanged or worsened. In contrast, the absence of psychiatric disorders was associated with remission of headaches after 8 years.
Comorbid depression or anxiety is a negative prognostic indicator for patient compliance across a wide variety of medical conditions, including headache.15 Patients with MOH syndromes are particularly at risk for mood, anxiety, and psychoactive substance use disorders, and certain psychological states may play a key role in headache medication overuse (eg, fear of headache, anticipatory anxiety, obsessional drug-taking behaviors, psychological drug dependence).16 Headache patients with personality disorders (particularly cluster B disorders—antisocial, borderline, histrionic, narcissistic) are especially likely to be nonadherent.17 This negative prognosis associated with psychiatric comorbidity emphasizes the importance of psychological assessment and identification of psychopathology among headache sufferers.
Potential mechanisms of comorbidity
Several mechanistic hypotheses might account for the comorbidity of migraine and psychiatric disorders, including serotonergic dysfunction, ovarian hormone influences (for women), and processes perpetuating central sensitization.18 None of these is likely to be the sole contributor. Central serotonergic dysfunction is the explanation most commonly proffered, because the pharmacological agents of choice for depression/anxiety (ie, SSRIs and SNRIs) and for acute migraine (ie, triptans) are those that increase central serotonergic availability. A lowered serotonergic disposition predisposes migraineurs to cortical spreading depression (the source of migraine aura) and subsequent sensitization of trigeminovascular pathways.19
The female preponderance of migraine and affective comorbidities argues also for a strong role of hormonal influences. Precipitous drops in estrogen levels, such as those that occur during menstruation and perimenopause, are linked both to migraine attacks and affective disturbance. Obviously, large declines in estrogen are not relevant for male migraineurs. Among persons with chronic migraine, central sensitization and dysregulation of the hypothalamic-pituitary-adrenal axis also have been implicated. These 3 hypotheses await further research.
