Dopamine D<sub>2/3</sub>R availability after discontinuation of antipsychotic treatment: a [<sup>11</sup>C]raclopride PET study in remitted first-episode psychosis patients
Franciska de Beer, Erik F. J. de Vries, Ben Wijnen, Marieke Begemann, Nico van Beveren, Nynke Boonstra, Shiral S. Gangadin, Lieuwe de Haan, Iris M. H. Hamers, Wim Veling, Sanne Koops, Iris E. Sommer
Abstract
Abstract Background After remission of a first-episode psychosis (FEP), antipsychotic discontinuation is associated with an increased risk of relapse compared to maintenance treatment. We studied short and longer-term effects of discontinuation of D 2 receptor (D 2 R) antagonist and partial agonist antipsychotics on striatal dopamine D 2/3 R availability in FEP patients. Methods Remitted FEP patients underwent two [ 11 C]raclopride PET scans to measure striatal D 2/3 R availability: 1 week after antipsychotic discontinuation (n = 16 antagonist users, n = 6 partial agonist users) and after being medication free for 6–8 weeks (n = 8 antagonist users, n = 5 partial agonist users). Fifteen matched healthy controls were scanned once. Psychotic relapse was monitored up to 12 months after discontinuation. Results One week after discontinuation, D 2 R antagonist discontinuers showed higher striatal binding potential (BP ND ) than partial D 2 R agonist discontinuers ( p < 0.001, CI = 0.749 to 1.681) and controls ( p = 0.045, CI = 0.008 to 0.708), while partial agonist discontinuers had significantly lower BP ND than controls ( p = 0.001, CI = -1.326 to -0.386). 6-8 weeks after discontinuation, former antagonist users showed similar BP ND to controls ( p > 0.25), whereas former partial agonist users had higher BP ND than controls ( p = 0.027, CI = 0.069 to 1.085). Participants who discontinued antagonists relapsed more often (81%) than those who discontinued partial agonists (17%)(χ 2 = 5.32, p = 0.021). Conclusions Discontinuation of partial D 2 R agonists may affect D 2/3 R availability differently than discontinuation of antagonists, which might explain the greater relapse risk after tapering antagonists than partial agonist antipsychotics.