Practical Psychopharmacology: Using a Knowledge of Pharmacokinetics to More Rapidly Stabilize Patients at Lower Drug...

Three drug dosing strategies can be employed to address dose-dependent drug adverse effects. The usual strategy is to continue the drug but at a lower dose; it would then take 5 half-lives of the drug for the new steady state to be attained and for a dose-dependent adverse effect to correspondingly attenuate. Such slow offset of the adverse effect could be disadvantageous for drugs such as fluoxetine, penfluridol, and cariprazine that have long half-lives. A second strategy is to stop the drug and to resume it at a lower dose when the adverse effect attenuates as the drug blood level falls. This strategy introduces subjectivity in timing the reintroduction of the drug, requires closer patient monitoring, and risks nonadherence and relapse. The third strategy is to stop the drug for a prespecified number of days and to then reintroduce it at a lower dose. From a knowledge of pharmacokinetics, it can be shown that stopping a drug for just 1 half-life and then resuming it at half the dose results in the immediate achievement of steady state; that is, there is no need to wait for 4 additional half-lives as with the usual strategy of dose reduction without dosing interruption. A limitation of this pharmacokinetically driven dosing strategy, however, is that it would work well in the average patient but not in those with outlying pharmacokinetic parameters.