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Migraine, Psychiatric Comorbidities, and Treatment
Randolph W. Evans, MD; Noah Rosen, MD
Posted: September 2008  
Headache   2008;48:952-958

Caring for patients with more than one condition is often a challenge, particularly when those conditions cross over into other fields of medicine. Depression, anxiety, and bipolar illness are common problems which may complicate the diagnosis and treatment of many of our migraine patients.

Clinical History:   A 28-year old woman has had migraine without aura since the age of 13 with attacks now occurring about 4 times per month with an inconsistent response to triptans. In addition, she has had recurring endogenous depression for 3 years treated with paroxetine over one year ago with some help. Her depression is currently mild. There is no history to suggest hypomania or mania. She has been frequently anxious for a few years as well, worrying about everything, which can cause difficulty falling asleep. Her mother has a history of major depression and migraine. Her sister is being treated for migraine and bipolar disease.


  1. Is migraine co-morbid with psychiatric disorders?
  2. Is there a genetic basis?
  3. Does the psychiatric disorder (e.g. depression, anxiety, and bipolar disease) precede or follow the onset of migraine?
  4. Is depression more prevalent in those with chronic migraine as compared with those with infrequent migraine?
  5. Should the psychiatric disorder alter the treatment of migraine?
  6. What preventive medication would be helpful in this case?
  7. What about for migraine and bipolar disease?

Expert Opinion:
One of the major reasons that patients come to see headache specialists is due to failure to respond to typical treatment. If her initial diagnosis is accurate but she has not responded to typical treatment, often, her primary care physician, family practitioner, or obstetrician/gynecologist will refer her to more specialized care. The aspects of failure to respond most likely include increasing frequency of headache, increased disability from pain and associated features, lack of adequate acute relief from medication with prolonged, disabling attack and higher migraine index ratings. Complicating features of care include unclear diagnosis of headache, secondary headaches, side effects from medications, and comorbid illness.

In this case, the patient in question presents with a history of depression not otherwise specified, anxiety disorder not otherwise specified, insomnia, and fairly frequent migraine with poor response to treatment. Her care requires understanding of the relationship between her multiple diagnoses and treatment options.

Is migraine co-morbid with psychiatric disorders? Is there a Genetic Basis? Over 50% of those people in the general population with migraine never receive the diagnosis. Of those diagnosed and referred to specialists, rates of comorbid illness may reflect a much higher rate than the general population. However, that being said, there is a moderate body of evidence over the past 50 years for significant mood and anxiety disorders in the general population with migraine as well as in specialistsí offices.

Is Depression more prevalent in those With Chronic Migraine as compared with those with infrequent migraine? As headache frequency increases, the risk of depression and anxiety also appears to increase. Chronic daily headache has greater comorbidity than episodic migraine. In fact, chronic daily headache patients may have over 90% chance of comorbid psychiatric disorder.

Does the psychiatric disorder (eg, depression, anxiety, and bipolar disease) precede or follow the onset of Migraine? Anxiety disorders tend to precede the age of onset of depression and migraine and there has been historical speculation that the disorders may represent a continuum. The mean age of onset for anxiety is 12 years, the mean age of onset for migraine is 15 years, and the mean age for depression is 17 years. There is no clear relationship between new episodes of major depression and migraine attack frequency.

Should the psychiatric disorder alter the treatment of Migraine? Patients with migraine and comorbid depression, anxiety, and bipolar illness other require individualized treatment. It is a good rule of thumb to think that medical treatment of migraine should be tailored both to the individual attack and also to the individual.

What preventive medication would be helpful in this case? Antidepressant medications fall into several different groups: tricyclics, SSRIs, SNRIs, norepinephrine dopamine reuptake inhibitors, monoamine oxidase inhibitors, and atypical or other medications. The relative potency and efficacy of these medications with regards to their antidepressant effect is the matter of much debate. Some studies suggest that the newer agents are not necessarily more effective, but have a lower incidence of side effects, leading to improved compliance with treatment and greater patient satisfaction. Similarly, many of these medications also demonstrate anxiolytic effects of varying degrees. A number of these medications have been studied with regards to migraine prevention with a range of efficacy as well.

What about for Migraine and Bipolar Disease? Considerations for bipolar disease may have a significant change in our choice of medications. The fact that this patient has a first degree relative with bipolar illness raises her risk above that of the general population. The unrestricted effect of an antidepressant therapy has the risk of uncovering the bipolar diathesis and leading to a hypomanic or manic episode. This would require significant alteration in pharmacotherapy. Several medications used for bipolar treatment have also been used for migraine therapy.

While this article may provide some general guidelines to care, the determination of prophylaxis should be tailored to both the individual and to the attack. Ignoring the coexistence of psychiatric disorders in migraine sufferers may limit the ability to treat someone appropriately and effectively. Even after the initial drug selection is made, adjustments may need to be made, fallback strategies considered, and adverse events monitored.