Dopamine D2/3R availability after discontinuation of antipsychotic treatment: a [11C]raclopride PET study in remitted first-episode psychosis patients.

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 D₂ receptor (D₂R) antagonist and partial agonist antipsychotics on striatal dopamine D_2/3R availability in FEP patients.

Methods: Remitted FEP patients underwent two [¹¹C]raclopride PET scans to measure striatal D_2/3R 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, D₂R antagonist discontinuers showed higher striatal binding potential (BP_ND) than partial D₂R 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%)(χ² = 5.32, p = 0.021).

Conclusions: Discontinuation of partial D₂R agonists may affect D_2/3R availability differently than discontinuation of antagonists, which might explain the greater relapse risk after tapering antagonists than partial agonist antipsychotics.