The article by Kay et al1 confirms in an elegant way that a first-generation antihistamine, diphenhydramine, is sedating and affects performance when given to healthy volunteers, an effect that has been recognized by the medical community and patients for perhaps half a century, and that this does not occur with a second-generation drug, loratadine. Unfortunately, this information is not useful to the clinician for the following reasons: (1) Diphenhydramine is usually prescribed for rhinitis at bedtime, not 4 times per day. (2) Healthy volunteers are not the same as patients with allergic conditions. (3) The attempt to generalize the information to all first-generation antihistamines fails since the authors did not select the least sedating of the first-generation drugs. (4) An advocate for diphenhydramine, a generic drug, would not accept their protocol, whereas an advocate for the second-generation drug would find the protocol ideal.
Aelony Y. First-Generation vs Second-Generation Antihistamines. Arch Intern Med. 1998;158(17):1949-1950. doi: