In order to devise more effective and safe pharmacotherapies for patients with refractory mood disorder, a number of pharmacokinetic properties of several psychotropic drugs are being studied. Recently, our group reported carbamazepine, but not valproate therapy, decreased single point (150 mg dose) bupropion pharmacokinetics (maximal concentration and 24 hour area under the curve). Secondly, levels of hydroxybupropion, a major active metabolite, were increased in both carbamazepine and valproate, but a decrease in the bupropion/hydroxybupropion ratio was only present in the carbamazepine group. The clinical impact of this differential pharmacokinetic finding remains to be fully explored, but may be the reason that bupropion levels are essentially undetectable during carbamazepine treatment. A third group of studies currently under investigation are the single point pharmacokinetics of two new, recently FDA-approved, anticonvulsants -- gabapentin (Neurontin(R)) and lamotrigine (Lamictil(R)). As it is likely that these medications will be used in rational polypharmacy algorithms, we plan to conduct similar pharmacokinetic parameter studies of each anticonvulsant and determine whether significant pharmacokinetic drug interaction exists with lithium carbonate. Our preliminary data to date suggest that lithium levels are not affected by either of these compounds.
