Major
Alprazolam × Amitriptyline
Benzodiazepines. Short-to-medium-acting anxiolytics×Tricyclic antidepressants (TCA)
Mechanism
Additive CNS depression, sedation, and anticholinergic effect. In older patients: high delirium and fall risk.
Symptoms
Deep sedation, drowsiness, ataxia, confusion (especially in older patients). Dry mouth, constipation, urinary retention (anticholinergic effect).
Management
Avoid the combination in older patients. If needed, use the minimum effective dose of both with a short course. Alternative anxiolytic when a TCA is needed: hydroxyzine or gabapentinoids.