Amitriptyline Sodium valproate

A man with severe pain, well controlled with amitriptyline, sodium valproate and intrathecal boluses of diamorphine, experienced severe pain within 5 minutes of an intrathecal test dose of clonidine 75 mierograms. ... 

Amitriptyline and nortriptyline plasma levels can be increased by sodium valproate and valpromide, but in contrast, an isolated report attributes a paradoxical rise in serum desipramine levels to the withdrawal of valproic acid. Valproate pharmacokinetics may be moderately affected by amitriptyline. Status epilepticus has been attributed to elevated clomipramine levels in a patient taking valproic acid. 

In one study, 15 healthy subjects were given a single 50-mg dose of amitriptyline 2 hours after taking the ninth dose of semisodium valproate 500 mg every 12 hours. The maximum plasma levels and AUC of amitriptyline were raised by 19% and 30%, respectively. The corresponding values for the nortriptyline metabolite were 28% and 55%, respectively. A study in 6 patients with depression found that amitriptyline 100 mg daily for 3 weeks produced a 43% increase in the volume of distribution and a 16% increase in the plasma half-life of a single 400-mg intravenous dose of sodium valproate. The AUC and total body clearance of valproate were not significantly changed. ... 

---