Lithium use associated with symptom severity in comorbid bipolar disorder I and migraine

Bipolar disorder (BD) and migraine headaches are frequently comorbid. The common etiological features are unknown, however cortical hyperexcitability (EEG) of migraines, and the report of hyperexcitability in pluripotent stem cell-derived neurons from lithium responsive BD subjects offers a physiological hypothesis of excitable neurons linking these disorders. However, clinical studies suggest that a history of migraine is associated with higher rates of relapse in those with BD taking lithium. Lithium use and history of migraine in this prospective longitudinal study of BD find that lithium use is associated with a greater symptom severity in BD.

Data on longitudinal outcome from 538 patients with BD I were categorized according to treatment with lithium and comorbidity with migraine. Clinical outcome measures on depression, mania, and quality of life over the most recent 2-year period compared the BD and BD/migraine cohort according to lithium treatment status.

A history of migraines was associated with worse clinical outcomes of depression (p = .002), mania (p = .005), and mental and physical quality of life (p = .004 and p = .005, respectively), independent of lithium use. The BD/migraine cohort treated with lithium was associated with worse symptoms of mania, whereas those without migraine and lithium use were associated with milder manic symptoms (p = .026).

Herein, we replicate the relatively worse outcome in BD with comorbid migraine. We find evidence to suggest that lithium use is associated with more severe symptoms of mania among those with BD and a history of migraine and conclude that lithium is contraindicated in BD comorbid with migraine.