Currently, there are many studies on the co-morbidity of migraine and depression, and most scholars believe that the relationship between migraine and depression is bidirectional, with the former increasing the risk of the latter, and vice versa. There may be associations between migraine and depression in terms of etiology, pathophysiologic mechanisms, and clinical manifestations, and a proper understanding of these associations may alter future treatment strategies and improve patient prognosis. However, the true nature of the relationship is still being explored and researched. We do not know whether migraine prompts depression or depression induces migraine. It is also unclear whether the two are different manifestations of a single pathway. Treating migraine combined with depression is challenging. Not all antidepressants can be used to treat migraine, and not all medications used to treat migraine can be used to treat depression.5-Hydroxytryptamine reuptake inhibitors are widely used in the treatment of depression, but are usually not very useful in the prevention of migraine. Amitriptyline can be used to treat migraines, but is not usually used to treat major depression. Bipolar disorder is another comorbid mood disorder in migraine sufferers, affecting 2-4% of the population, with a lifetime prevalence of 40% (44% of women and 31% of men). The prevalence of bipolar disorder type 1 is close to 1% and is about the same in women and men. The prevalence of bipolar disorder type II ranges from 0.3% to 5.0%, and women are at risk for alcohol abuse. The lifetime prevalence of co-morbidity between migraine and bipolar disorder type II is 65% (75% in women and 40% in men). The correlation between migraine with aura and bipolar disorder has been reported in the literature to be three times higher than migraine without aura. Bipolar disorder type II is often misdiagnosed as major depression, so it is especially important to make the correct determination. The results of one study showed that 34.3% of migraineurs were diagnosed with a psychiatric disorder, with 4.9% diagnosed with bipolar disorder type 1 and 7.8% diagnosed with bipolar disorder type II. Patients with bipolar disorder have a higher frequency of depressive episodes than mania (nearly 3:1), and almost half of the time exhibit somatic symptoms. In the treatment of bipolar disorder, the application of antidepressants may induce transthyretic or hypomanic episodes, or increase the frequency of cycling, or promote rapid cycling episodes and make treatment more difficult. Therefore, antidepressants should be used with caution during depressive episodes in patients with bipolar disorder.