Confounding of Antipsychotic Discontinuation Studies by Withdrawal-Related Relapse.

Abstract

Schoretsanitis et al conclude from their reanalysis of individual patient data that most people relapse when they stop antipsychotics but the risk of relapse is greater by about a factor of 4 in those who stop oral medication compared with those who stop depot medication.1 It is perhaps no accident that depot antipsychotic concentrations slowly fall over months in an exponential manner, partially mimicking the gradual, hyperbolic antipsychotic reduction recently proposed.2 There are 2 possible explanations for a lower relapse rate from depot medication compared with oral and one or both might be relevant. The first is that the small amount of antipsychotic that remains for months after stopping depots is enough to prevent relapse in some patients. This explanation is of interest because it suggests that very low concentrations of antipsychotic (after 5 half-lives, drug levels will only be 3% of original) are enough to prevent relapse. This is consistent with previous findings3 and the knowledge that low concentrations of antipsychotic produce higher receptor occupancy than might be expected.4 It is also possible that the small residual doses may function to delay the onset of withdrawal-related effects.