Antihistamines
Due to their ease of availability, this is 1 of the most common classes of drugs that is bothersome to patients with RLS. There is no medical literature to substantiate this association, but extensive clinical experience supports this effect. These drugs are prevalent in OTC sleeping pills (diphenhydramine, doxylamine) and OTC cold remedies (often in combination with other drugs, which makes their presence even less obvious). Alternatives to their use include the newer second generation H1 blockers (loratadine, fexofenadine, desloratadine, and possibly cetirizine) that do not cross the blood-brain barrier and thus do not worsen RLS symptoms.
Anti-Nausea and Anti-Emetic Drugs
Many anti-nausea drugs (trimethobenzamide, prochlorperazine, promethazine, hydroxyzine (both are Antihistamines), meclizine, and metoclopramide) block the dopamine system and thus may worsen RLS [56]. Alternatives include the newer selective 5-HT3 receptor antagonists (granisetron hydrochloride, ondansetron hydrochloride), which do not bind to the dopamine receptors [57], and the peripherally acting drug domperidone (not available in the United States [U.S.]), which does not cross the blood-brain barrier and does not affect RLS