Minor
Amitriptyline × Levetiracetam
Tricyclic antidepressants (TCA)×Antiepileptics (other)
Mechanism
Levetiracetam is not metabolised by the CYP system; no pharmacokinetic interaction with amitriptyline. Mild additive CNS depression is possible.
Symptoms
Possible mild sedation and fatigue at the start; usually resolve within 1–2 weeks.
Management
No dose adjustment needed. In epilepsy with depression or neuropathic pain, the combination is reasonable. Amitriptyline lowers seizure threshold at high doses, so begin with minimal doses (10 mg at bedtime) and monitor seizure frequency.