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

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Title: Dopamine D2/3R availability after discontinuation of antipsychotic treatment: a [11C]raclopride PET study in remitted first-episode psychosis patients: a [11C]raclopride PET study in remitted first-episode psychosis patients.
Authors: Franciska de Beer, Erik de Vries, Ben Wijnen, Marieke J.H. Begemann, Nico van Beveren, Nynke Boonstra, Shiral S. Gangadin, Lieuwe de Haan, Iris M.H. Hamers, Wim Veling, Sanne Koops, Iris E.C. Sommer
Source: Psychological Medicine. 55
Publisher Information: Cambridge University Press (CUP), 2025.
Publication Year: 2025
Subject Terms: Male, Adult, positron emission tomography, antipsychotic discontinuation, First-episode psychosis, Dopamine D3/metabolism, antipsychotic medication, Young Adult, Dopamine D2 Receptor Antagonists, psychotic relapse, Raclopride, Recurrence, Corpus Striatum/metabolism, Positron-Emission Tomography, Case-Control Studies, Receptors, Humans, Female, Dopamine D2/metabolism, dopamine, Psychotic Disorders/drug therapy, Antipsychotic Agents/therapeutic use
Description: 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.
Document Type: Article
Language: English
ISSN: 1469-8978
0033-2917
DOI: 10.1017/s003329172510161x
Access URL: https://research.rug.nl/en/publications/4d50a15f-b7d5-4a85-87e5-858e73fbd9af
https://hdl.handle.net/11370/4d50a15f-b7d5-4a85-87e5-858e73fbd9af
https://doi.org/10.1017/S003329172510161X
https://pure.amsterdamumc.nl/en/publications/930232ab-3d7b-435a-afa6-bbf4e4b9228e
https://doi.org/10.1017/S003329172510161X
Rights: CC BY
Accession Number: edsair.doi.dedup.....6f3bc32d94b6fedc37b95a7c9f35b6ce
Database: OpenAIRE
Description
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 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.
ISSN:14698978
00332917
DOI:10.1017/s003329172510161x