Moderate
Alprazolam × Pregabalin
Benzodiazepines. Short-to-medium-acting anxiolytics×Gabapentinoids (antiepileptics)
Mechanism
Additive CNS depression via different mechanisms (GABAergic for alprazolam, α2δ calcium channel blockade for pregabalin). Sedation, ataxia, and fall risk amplify, especially in older patients.
Symptoms
Sedation, fatigue, slowed reactions, impaired coordination. In older patients: fall and fracture risk. Driving and operating machinery: accident risk. Ataxia and fall risk are especially pronounced in older patients.
Management
On starting the combination, begin both at minimal doses. Avoid the combination in older patients — fall and fracture risk. In neuropathic pain and anxiety, alternative: low-dose amitriptyline with buspirone, or duloxetine with CBT. If unavoidable, give alprazolam only at bedtime.