Oral antihistamines lose their effectiveness when taken chronically.

  Some people who initially get relief from their antihistamines say that their allergic symptoms return within a couple of weeks or months.

  Patients taking first generation antihistamines (Benadryl, chlorpheniramine, etc) seem to be the ones who complain of this.

  A couple of older studies suggest that chlorpheniramine loses its ability to suppress the wheal and flare reaction after chronic dosing.