Decrease in Erythrocyte:Plasma Lithium Ratio by Concurrent Administration of Psychotropic Drugs and Lithium in Mice

1. Previous studies paying attention to concurrent use of lithium (Li +) with a neuroleptic were not done under constant and controlled conditions. We were therefore encouraged to do a prospectively controlled study, presuming constant relevant factors, on concomitant use of Li + with neuroleptic as well as other psychotropic agents. 2. The effects of concurrent administration of chlorpromazine, haloperidol, imipramine and carbamazepine with Li + on the erythrocyte:plasma Li + ratio and the intraerythrocyte Li + concentration were studied in mice by using a new, direct method of measuring erythrocyte Li + concentration. 3. All of the foregoing agents with the exception of carbamazepine were observed to significantly decrease the Li + ratio. 4. Lack of any significant effect by carbamazepine on Li + transport may be an indication of this drug’s efficacy as a supplement in Li + therapy of bipolar affective disorders. 5. The decrease in Li + ratio observed with chlorpromazine, haloperidol and imipramine may be explained through the mechanism by which these drugs stabilize the cell membrane and consequently affect Li + transport in erythrocytes. 6. Moreover, our study proves that, although the Li +–sodium countertransport mechanism does not exist in mice, the same interaction between Li + and other psychotropic drugs is seen. It can be concluded that such interaction is not mediated through Li +–sodium countertransport. 7. It is suggested that, with concurrent use of a psychotropic drug and Li +, the amount of intraerythrocyte Li + concentration be measured, instead of relying on the plasma Li + concentration alone.