Psychological medicine · 2025
Dopamine D2/3R availability after discontinuation of antipsychotic treatment: a [11C]raclopride PET study in remitted first-episode psychosis patients.
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de Beer Franciska, de Vries Erik, Wijnen Ben, Begemann Marieke J H, van Beveren Nico, Boonstra Nynke, Gangadin Shiral S, de Haan Lieuwe, Hamers Iris M H, Veling Wim, Koops Sanne, Sommer Iris E C
Аннотация
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 D2/3R availability in FEP patients.
METHODS: Remitted FEP patients underwent two [11C]raclopride PET scans to measure striatal D2/3R 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 (BPND) 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 BPND than controls (p = 0.001, CI = -1.326 to -0.386). 6-8 weeks after discontinuation, former antagonist users showed similar BPND to controls (p > 0.25), whereas former partial agonist users had higher BPND 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 D2/3R availability differently than discontinuation of antagonists, which might explain the greater relapse risk after tapering antagonists than partial agonist antipsychotics.
METHODS: Remitted FEP patients underwent two [11C]raclopride PET scans to measure striatal D2/3R 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 (BPND) 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 BPND than controls (p = 0.001, CI = -1.326 to -0.386). 6-8 weeks after discontinuation, former antagonist users showed similar BPND to controls (p > 0.25), whereas former partial agonist users had higher BPND 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 D2/3R availability differently than discontinuation of antagonists, which might explain the greater relapse risk after tapering antagonists than partial agonist antipsychotics.