James R O'Neill, Christopher Wilson, Mark A Horowitz, Samantha L McLean, Muhammad Faisal, Michael Dixon, Lewis Couchman, Katie Lawlor, George Crowther
{"title":"Correlations between receptor occupancy change and mental state in patients using long-acting injectable antipsychotics: MIDILIA pilot study.","authors":"James R O'Neill, Christopher Wilson, Mark A Horowitz, Samantha L McLean, Muhammad Faisal, Michael Dixon, Lewis Couchman, Katie Lawlor, George Crowther","doi":"10.1192/bjo.2025.10831","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The rate at which psychosis drugs can be reduced in dose remains unclear. Anecdotal reports exist of people experiencing worsening of mental state before their next dose of long-acting injectable antipsychotic. No research has previously explored this phenomenon, but understanding this may advise on the rate of receptor occupancy change that provokes the emergence of psychotic symptoms.</p><p><strong>Aims: </strong>Exploring the relationship between psychotic symptoms and variations in plasma concentration (and calculated receptor occupancy) of long-acting injectable antipsychotics.</p><p><strong>Method: </strong>This longitudinal study monitored mental state variation within dosing cycles of people taking depot flupentixol and zuclopenthixol. The Positive and Negative Syndrome Scale (PANSS) monitored global mental state changes, and was stratified into domains according to a five-factor model. Plasma assays at maximal and minimal concentrations allowed prediction of striatal D<sub>2</sub> occupancy from published data. We examined correlations between receptor occupancy and the emergence of psychotic symptoms.</p><p><strong>Results: </strong>Preliminary results from ten participants with psychotic disorders suggest that global mental state deterioration may correlate with increased rate of D<sub>2</sub> occupancy reduction. Increased rate of D<sub>2</sub> occupancy reduction led to deterioration in 'positive' (<i>r</i> = 0.637 [CI: 0.013, 0.904], <i>P</i> = 0.047) and 'resistance' (<i>r</i> = 0.726 [CI: 0.177, 0.930], <i>P</i> = 0.018) PANSS clinical domains at minimal concentrations. PANSS score differences were not related to absolute reduction in D<sub>2</sub> occupancy.</p><p><strong>Conclusions: </strong>Our novel observational study design has been demonstrated to be feasible and practicable. Faster reductions in D<sub>2</sub> occupancy may increase the risk of increased positive psychotic symptoms and irritability. Slower reductions may minimise this effect. Further recruitment is required before this can be confirmed.</p>","PeriodicalId":9038,"journal":{"name":"BJPsych Open","volume":"11 5","pages":"e211"},"PeriodicalIF":3.5000,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12451532/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"BJPsych Open","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1192/bjo.2025.10831","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PSYCHIATRY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: The rate at which psychosis drugs can be reduced in dose remains unclear. Anecdotal reports exist of people experiencing worsening of mental state before their next dose of long-acting injectable antipsychotic. No research has previously explored this phenomenon, but understanding this may advise on the rate of receptor occupancy change that provokes the emergence of psychotic symptoms.
Aims: Exploring the relationship between psychotic symptoms and variations in plasma concentration (and calculated receptor occupancy) of long-acting injectable antipsychotics.
Method: This longitudinal study monitored mental state variation within dosing cycles of people taking depot flupentixol and zuclopenthixol. The Positive and Negative Syndrome Scale (PANSS) monitored global mental state changes, and was stratified into domains according to a five-factor model. Plasma assays at maximal and minimal concentrations allowed prediction of striatal D2 occupancy from published data. We examined correlations between receptor occupancy and the emergence of psychotic symptoms.
Results: Preliminary results from ten participants with psychotic disorders suggest that global mental state deterioration may correlate with increased rate of D2 occupancy reduction. Increased rate of D2 occupancy reduction led to deterioration in 'positive' (r = 0.637 [CI: 0.013, 0.904], P = 0.047) and 'resistance' (r = 0.726 [CI: 0.177, 0.930], P = 0.018) PANSS clinical domains at minimal concentrations. PANSS score differences were not related to absolute reduction in D2 occupancy.
Conclusions: Our novel observational study design has been demonstrated to be feasible and practicable. Faster reductions in D2 occupancy may increase the risk of increased positive psychotic symptoms and irritability. Slower reductions may minimise this effect. Further recruitment is required before this can be confirmed.
期刊介绍:
Announcing the launch of BJPsych Open, an exciting new open access online journal for the publication of all methodologically sound research in all fields of psychiatry and disciplines related to mental health. BJPsych Open will maintain the highest scientific, peer review, and ethical standards of the BJPsych, ensure rapid publication for authors whilst sharing research with no cost to the reader in the spirit of maximising dissemination and public engagement. Cascade submission from BJPsych to BJPsych Open is a new option for authors whose first priority is rapid online publication with the prestigious BJPsych brand. Authors will also retain copyright to their works under a creative commons license.