Lithium and phenytoin may act synergistically to cause CNS toxicity even at therapeutic lithium concentrations, particularly in patients with pre-existing brain damage.
single dose of lithium or phenytoin sodium was given to the rats before administering tranylcypromine (a monoamine oxidase inhibitor) plus L-tryptophan.Moreover, if either drug was given in multiple doses over two days there was a pronounced increase in brain synthesis of serotonin.Although they did not examine the combined effects of lithium and phenytoin sodium, they drew attention to their similar action.Possibly the two drugs acted synergistically in our patient, with the resultant toxicity despite normal serum lithium concentra- tions.A third factor is that our patient probably had pre-existing minimal brain damage, which would explain his odd personality, abnormal EEGs, and history suggestive of epilepsy.There is the remote possibility that such patients have an abnormally low tolerance to lithium.All three hypotheses bear further investigation and should be considered if further cases of CNS toxicity occur in patients with therapeutic lithium concentrations.In general, closer observation should be kept for the possible synergistic action of drugs in patients who develop severe side effects.
Mieghem et al. (1978) studied this question.