HTR1B and migraine disorder: 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.