Nortriptyline Sodium valproate

The authors concluded that the features of the illness were consistent with nortriptyline-induced neuroleptic malignant syndrome (82). However, a contributory role for sodium valproate was also possible. 

A 69-year-old man with bipolar disorder, who had been taking venlafaxine up to 337.5 mg daily, thioridazine 25 mg at night, and sodium valproate 1.2 g daily for several months with no adverse motor symptoms, experienced extrapyramidal effects 3 to 4 days after the venlafaxine had been gradually replaced by nortriptyline 50 mg daily. Symptoms persisted despite withdrawal of thioridazine, but improved on reduction of the nortriptyline dosage to 20 mg daily. The cause of the reaction was not known, but it was suggested that there may have been an interaction between venlafaxine and nortriptyline possibly modulated by thioridazine or sodium valproate. 

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. ... 

---