lamotrigine-divalproex interaction timing

(Updated 7/2015)

Summary: How fast does the interaction take place? is it like carbamazepine, cranking up over a few weeks? or immediate? And what dose of divalproex is sufficient to begin the interaction?

Answer: immediate; at 125-500 mg in adults, becoming maximal by as little as 250 mg.

From this reference in 1992; and even better, this reference in 2004

Inhibition of lamotrigine metabolism is already maximal at dosages of valproate around 500 mg/ day, resulting in roughly a doubling of lamotrigine levels. What about lower divalproex doses?

The older reference above did not suggest the results found in the direct test described in the newer one above, which found:

divalproex dose (mg) Increase in lamotrigine (%)
125 30
250 50
375 50
500 50

In some ways this makes life easier. When the patient is on lamotrigine and divalproex is added, simply cut the lamotrigine dose in half right as you start this addition.

The other direction

Initially I was taught “they each double each other’s levels.” I can’t find a reference for that, in terms of lamotrigine’s effects on valproate levels. Instead, the only thing I can find suggests that lamotrigine is associated with a moderate reduction in valproate levels, as much as 25%. Anderson