Spontaneous MAOI hypertensive reaction, not likely armodafinil -tranylcypromine interaction

I read with interest the recent case report by Kinslow et al. describing what they believe to be an acute hypertensive crisis from the concurrent use of armodafinil and tranylcypromine [ ]. The authors noted one prior case report of an acute reaction with a similar combination (actually involving the racemic compound modafinil). But, in point of fact, that case, reported by Vytopil el al [ ], appears to actually describe a clinical condition closer to a serotonin syndrome, not an acute hypertensive crisis [ ]. The mechanisms of action of these two problematic interactions, a hypertensive reaction and serotonin syndrome, are rather different [ ]. As the authors review, there are no other cases in the literature of an acute hypertensive reaction to this combination, but rather there are a number of cases of the safe concurrent use of modafinil and an MAOI. This coincides with my experience as well in safely combining MAOIs with modafinil. Rather than a drug- drug toxic interaction one can offer an alternative explanation, with better support in the literature, for the hypertensive crisis in Kinslow's patient. That is, a spontaneous hypertensive crisis due solely to the MAOI. There are multiple reports in the literature of spontaneous intense acute hypertensive crises to MAOI monotherapy [ ]. Most reports are associated with tranylcypromine and not uncommonly occurring upon dose increase, as noted in this case report [ ]. While the mechanism of action of these spontaneous reactions are not clear these hypertensive crises clinically mimic those seen classically with MAOIs and tyramine ingestion [ ]. I would suggest that the latter is the more likely explanation in this case. More controlled research is needed to more definitively address the relative safety/danger of concurrent prescribing of an MAOI with armodafinil or modafinil.