Depression is another common condition linked to migraines. A 2000 study in the journal Neurology showed that people with migraines or other serious headache conditions are three times more likely to experience a major depression than the general population. Similarly, a 1994 study in the journal Headache found that patients with a history of major depression are 3.1 times more likely to experience the initiation of migraines than those without a history of depression.

These results, though powerful, do not necessarily suggest a cause-and-effect relationship between depression and migraine, or migraine and depression. The correlation between migraine and mood disorders such as depression could be rooted in the stress that comes from dealing with either condition. More likely, however, some underlying biological predisposition sets the stage for both conditions, creating the appearance of an association between the two.

Some drugs are available that can treat both conditions. If sleep is also disrupted due to the depression and migraines, the drug of choice may be an antidepressant such as amitriptyline (Elavil). This drug serves to help regulate the serotonergic pathways and treats both depression and migraine separately. At the same time, this drug may help with sleep disruptions, as it can be very sedating. However, amitriptyline can have other adverse side effects, and other similar drugs with less bothersome side effects, such as nortriptyline (Pamelor) are prescribed instead. Beta-blockers should not be used to treat migraines in patients who suffer from depression.

Selective serotonin reuptake inhibitors (SSRIs) have also been used to treat patients who suffer from both migraine and depression, but such drugs have shown only limited efficacy in clinical trials. Such drugs may be prescribed by physicians who believe that stress and anxiety can trigger migraines. Monoamine oxidase inhibitors (MAOIs) are also sometimes used for patients who suffer from depression as well as migraine.