It's typical for someone looking for relief from dry, itchy, red and irritated skin – also known as eczema or atopic dermatitis – to turn to common allergy medications called antihistamines. New research from McMaster University, however, has found that these commonly used medications don't make a meaningful difference in improving symptoms, and for some of the most commonly used antihistamines, they can cause harm.
Oral antihistamines are a common staple in households around the globe, with many available without a prescription. The belief is these medications will help temper down itching and disruptions to sleep caused by eczema, but clinical practice and guidelines vary in recommending for or against the potential benefits due to lack of clear evidence.
As detailed in the BMJ on July 29, 2026, researchers found that oral antihistamines do not importantly improve the outcomes that matter most in controlling eczema, and can increase the risk of cognitive impairment. To come to this conclusion, a systematic review of 47 randomized trials consisting of 6,230 children and adults with mild to severe eczema was conducted – the most comprehensive analysis to date on the topic.
"Eczema care increasingly focuses on controlling skin and immune inflammation with moisturizers, topical anti-inflammatory treatments , and whole-body treatments like phototherapy, biologics, and oral JAK inhibitors . That makes it important to know whether antihistamines add important benefit or mostly add treatment burden and harm," says senior author Derek Chu , associate professor with McMaster's Department of Medicine, Canadian Institutes of Health Research Chair in Allergy, and Lead of Canada's Allergy Clinical Trials Network.
The review looked at two categories of medications: modern, second-generation antihistamines and older, first-generation antihistamines. The study found that second-generation medications – commonly known under brand names such as Reactine, Claritin, Aerius, Allegra, Rupall, and Blexten – produced small changes in eczema severity and itch, but that relief fell short of what patients and their clinicians would consider as an important improvement.
First-generation antihistamines – commonly found under brand names such as Benadryl, Chlor-Tripolon and Polaramine – produced no noticeable improvement. These older medications, however, likely increase cognitive impairment, such as drowsiness, confusion, slowed thinking, or impaired school or work performance. Such impairments are increasingly recognized to last into the days after use. Among newer second-generation antihistamines, cognitive effects were much lower and differed by drug (bilastine, desloratadine, and fexofenadine being least sedating).
"The findings support moving away from routine antihistamine use in atopic dermatitis care and toward treatments that are more effective, less likely to cause harm, and are more certain to control eczema inflammation. This may also help keep eczema control as simple and straightforward as possible, with patients focusing on high-value treatments," says Chu, who holds a joint appointment with McMaster's Department of Health Research Methods, Evidence and Impact.
Researchers stress that oral antihistamines have a place in treating allergic conditions such as hay fever, seasonal allergies and hives.
The work was commissioned by the American Academy of Allergy, Asthma & Immunology and the American College of Allergy, Asthma and Immunology through the Joint Task Force on Practice Parameters for the living atopic dermatitis guidelines .
The study used the McMaster-developed grading of recommendations assessment, development and evaluation ( GRADE ), a leading global system for rating the certainty of evidence and translating evidence into clinical recommendations.
Aspects of the study were conducted with The Research Institute of St. Joe's Hamilton.
This McMaster-led research involved partners from Harvard T.H. Chan School of Public Health, Children's Hospital of Philadelphia/University of Pennsylvania, Boston Children's Hospital, National Jewish Health/University of Colorado, UMass Chan Medical School, Arizona State University, George Washington University, Northwestern University, University of Saskatchewan, Icahn School of Medicine at Mount Sinai, University of Rochester, University of Florida, Children's Hospital Los Angeles/USC, Lakehead University, and Tufts University.
People with lived experience and advocacy partners including the Asthma and Allergy Foundation of America, Global Parents for Eczema Research, National Eczema Association, and Allergy & Asthma Network were also involved.
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