Antihistamines Did Not Raise Dementia Risk

Second-generation antihistamines were not linked to higher dementia risk in older patients with allergic inflammatory diseases.
*Target trial emulation cohort study; Level 2b.

Citation

Olbrich H, Kolkhir P, Zuberbier T, Ludwig RJ, Metz M. Second-Generation H1-Antihistamines Do Not Alter Dementia Risk in Type 2 Inflammatory Diseases. J Allergy Clin Immunol Pract. 2026;14:2051-2058. doi:10.1016/j.jaip.2026.05.031

Background

Second-generation antihistamines are widely used for allergic and inflammatory conditions and are generally considered safe. Prior observational studies raised concern about dementia, but had important design limitations.

Patients

Patients aged 50 years or older with chronic urticaria, chronic sinusitis, or allergic rhinitis in a large United States health-record network. Patients with prior dementia, and in the target trial specification dementia-drug use, were excluded.

Intervention

Oral second-generation antihistamines; some analyses also assessed any oral antihistamine or first-generation antihistamines.

Control

Non-antihistamine alternatives: intranasal steroids for allergic rhinitis or chronic sinusitis; oral steroids for chronic urticaria. First-generation antihistamines were also comparators.

Outcome

First recorded dementia diagnosis.

Follow-up Period

Up to 5 years.

Results

ComparisonDementia finding
Any oral antihistamine versus non-antihistamine alternatives, all 3 diseasesNS
Second-generation versus first-generation antihistamines, all 3 diseasesNS
Second-generation antihistamines versus non-antihistamine alternatives in chronic urticaria or chronic sinusitisNS
Second-generation antihistamines versus intranasal steroids in allergic rhinitisHigher with antihistamines: HR 1.239 (95% CI 1.060 to 1.447)

NS = not statistically significant; HR = hazard ratio; CI = confidence interval.

Analyses used an intention-to-treat approach after matching on 38 baseline factors. Absolute event rates were not provided, so number needed to harm could not be calculated. Intranasal steroids are current standard treatment for allergic rhinitis when indicated.

Limitations

Despite target trial methods, this was still observational and cannot prove cause or safety. Over-the-counter antihistamine use, dose, adherence, long-term exposure beyond 5 years, and missing health-record data may be incompletely captured. The allergic rhinitis signal may reflect benefit from intranasal steroids rather than harm from antihistamines.

Funding

German public funding; funders uninvolved. Several authors had industry ties.

Clinical Application

Continue prescribing second-generation antihistamines when indicated; prefer intranasal steroids for allergic rhinitis symptoms, not because antihistamines appear to cause dementia.