Prolonged Pharmacologic Activity of Neuroleptics

To the Editor.— Many clinical and laboratory experiments are undertaken on the assumption that tissue levels or effects of neuroleptic agents have cleared by the time of investigation. A review of pertinent studies that appeared in theArchivesduring the 1984 indicates that the typical interval between discontinuing neuroleptic treatment and starting a study was approximately two weeks. Given the many previous reports that have set the plasma-elimination half-life of neuroleptics (usually after short-term administration in a small dose) in the range of 20 to 40 hours,1such an interval may seem adequate to assure substantial elimination of drug molecules. However, there is evidence that the pattern of elimination of neuroleptics may not be monophasic, and "terminal" plasma elimination rates of more than 60 hours have been noted.2In addition, "balance" studies of the input and output of neuroleptics typically find that a small, but possibly significant,