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.
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:
|Increase in lamotrigine
clearance time (%)
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