Examining Potential Mechanisms of Comorbid Bipolar Disorder and Migraine


In a systematic review, investigators aim to understand the mechanisms for comorbid bipolar disorder and migraine, as well as therapeutic targets.

bipolar disorder and migraine

In a review published in Frontiers in Psychiatry, investigators provided insights into the potential mechanisms of comorbid bipolar disorder (BD) and migraine, as well as therapeutic targets for the treatment.

There is a high prevalence of psychiatric illness in those with migraine disorder, yet a large proportion of affected patients are not diagnosed with any comorbid psychiatric disorder. BD is a severe psychiatric disorder characterized by recurrent episodes of manic/hypomanic or depressive symptoms and euthymic periods. According to the investigators, the prevalence of migraine in the BD population may be as high as 39%. Both diseases can lead to decreased quality of life and multiple dysfunction, and patients with comorbid BD and migraine typically have poorer treatment outcomes and increased disability.

For the review, the investigators conducted a systematic search of major databases PubMed and Embase from January 1991 to July 2020 using the search terms “bipolar disorder/s, manic depressive, manic depression comorbidity, and migraine.”

Multiple pathophysiological processes participate in the development of BD and migraine, according to the investigators. Research into the potential overlapping mechanisms of both conditions have focused on genetic factors, brain imaging, mitochondrial dysfunction, and inflammatory factors.

“Since there is a strong bidirectional association between migraine and BD, revealing the potential overlapping neurobiological mechanisms of these 2 diseases could promote the development of novel treatments,” the investigators wrote in the review.

There seems to be a common heritable link between BD and migraine, as parental migraine has been shown to be a risk factor for offspring BD. However, the investigators noted that BD is more closely related to comorbid migraine than parental migraine, suggesting nongenetic factors as well. It has also been reported that chronic inflammation, a disturbance of the balance between oxidative stress and the antioxidative stress response, and the regulation of nitrosative stress may also contribute to the pathophysiologic mechanisms of BD and migraine.

“Furthermore, targeting the inflammatory pathways may offer new pharmacological strategies,” the investigators wrote.

When it comes to potential treatments for patients with comorbid BD and migraine, there are currently no optimal alternatives. However, several pharmacologic treatments exist to help prevent the onset of both migraine attacks and acute manic or depressive episodes. These medications include valproate, lithium, lamotrigine, quetiapine, and topiramate. Despite these options, the investigators stressed that more needs to be done.

“In our opinion, although preventive medications, including mood-stabilizing agents and serotonergic agents, are widely used in patients with BD and migraine, respectively, additional effort is needed,” they wrote.

Identifying more effective and less toxic drugs can help address poor compliance and lead to better outcomes for patients. Future research examining the mechanisms of comorbid BD and migraine are necessary to move toward an effective treatment that targets the overlapping mechanisms at play.


  1. Duan J, Yang R, Lu W, et al. Comorbid bipolar disorder and migraine: From mechanisms to treatment. Frontiers in Psychiatry. January 11, 2021. doi: 10.3389/fpsyt.2020.560138

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