Moderate
Amitriptyline × Valproic acid
Tricyclic antidepressants (TCA)×Antiepileptics. Fatty acid derivatives
Mechanism
Valproate weakly blocks hepatic amitriptyline metabolism; TCA plasma levels may rise. Plus additive sedation.
Symptoms
Worsening anticholinergic symptoms, drowsiness, sedation. Older patients: delirium and fall risk.
Management
Reduce amitriptyline by 25% if needed when combined. In older patients, monitor cognition and fall risk. For neuropathic pain, alternative: gabapentin or pregabalin.