Not So Hasty: The Effect of Tapering Speed on Relapse May Still Be Important

We wish to congratulate Gangadin and colleagues on the completion of a landmark trial answering a key question regarding stopping antipsychotics after a first episode of psychosis.1 Their data show that more than half of patients with their first episode of psychosis (FEP) can stop antipsychotics without relapsing within 18 months of follow-up after remission, with even higher success rates for those who are taking low D2 affinity or partial agonist antipsychotics. However, we believe that the authors may have prematurely dismissed the role of tapering speed as a determinant of relapse, and that this conclusion is contradicted by some of their findings. It may be that with an even more gradual and hyperbolically patterned tapering process a greater proportion of FEP patients might be able to stop antipsychotic treatment without relapse. There is a debate in the literature regarding the primacy of a threshold model or a “velocity model” for risk of relapse on reducing dose of an antipsychotic.2 The threshold model of antipsychotic effects (the majority view) holds that if the dose of an antipsychotic is reduced below a certain threshold—about 65%-70% of D2 dopamine occupancy—relapse is likely in susceptible patients, with rate of reduction being of no importance. The “velocity model” suggests that relapse is in part due to withdrawal effects which can precipitate relapse either indirectly (via effects such as insomnia or agitation) or directly by lowering the threshold for psychosis owing to the persistence of dopaminergic hypersensitivity (DHS), or other receptor changes, induced by the antipsychotic treatment (“supersensitivity psychosis”).2 If DHS, or other adaptive changes, are indeed a factor, then if the drug is reduced more slowly and in a hyperbolic pattern the risk of relapse can be minimised.2 It may be that it is the degree to which the body can accommodate the rate of change to its homeostatic equilibrium which is important, rather than the extent of that change.3 An analogy might be made to altitude sickness in which absolute altitude is not the primary cause, but rather the rate of ascent.