The reduced occurrence of migraines with mirtazapine is attributed to its blockade of 5-HT2 (particularly 5-HT2B) and histamine receptors, which are implicated in migraine initiation.41 In addition, mirtazapine’s activation of 5-HT1 receptors, including 5-HT1B, 5-HT1D, and 5-HT1F, may alleviate migraines by constricting dilated cerebral vessels and reducing neurogenic inflammation.41 However, at higher doses, the activation of histamine may contribute to migraine recurrence. This evidence concerns the gene HTR2B and migraine disorder.