Moderate
Amitriptyline × Pregabalin
Tricyclic antidepressants (TCA)×Gabapentinoids (antiepileptics)
Mechanism
Similar to amitriptyline plus gabapentin — additive CNS depression. The combination is widely used in neuropathic pain, especially when monotherapy is insufficient.
Symptoms
Sedation, fatigue, slowed reactions, impaired coordination. In older patients: fall and fracture risk. Driving and operating machinery: accident risk.
Management
For neuropathic pain, start both at minimum doses: amitriptyline 10 mg at bedtime, pregabalin 75 mg twice daily. Up-titrate every 1–2 weeks as tolerated. Avoid in older patients — fall risk. Alternatives: duloxetine with topicals.