Moderate
Established
Description
Diphenhydramine adds to the sedative effects of alprazolam, increasing the risk of excessive CNS depression, falls, and cognitive impairment.
Mechanism
Diphenhydramine's CNS depressant effect (H1 blockade + anticholinergic) is additive to benzodiazepine-mediated GABA-A potentiation.
Clinical Significance
Particularly dangerous in elderly patients (Beers Criteria lists both drugs as potentially inappropriate); significantly raises fall risk.
Management
Avoid combination in elderly patients; use non-sedating alternatives and consider dose reduction if both are required.