Correlations between receptor occupancy change and mental state in patients using long-acting injectable
James R O'Neill1,2,3, Christopher Wilson2, Mark A Horowitz4,5
1School of Medicine, University of Leeds, UK.
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.
Insights
Faster reduction in dopamine D2 receptor occupancy during antipsychotic dosing cycles may worsen positive psychotic symptoms. Slower reductions may help minimize these effects, suggesting a link between receptor occupancy changes and symptom emergence.
Area of Science:
- Psychiatry and Pharmacology
- Neuroscience
- Clinical Psychopharmacology
Background:
- The optimal rate for reducing antipsychotic medication doses is not well-established.
- Anecdotal evidence suggests potential mental state worsening before the next long-acting injectable antipsychotic dose.
- Understanding these fluctuations may inform receptor occupancy changes that trigger psychotic symptoms.
Purpose of the Study:
- To investigate the relationship between psychotic symptoms and plasma concentrations (and estimated receptor occupancy) of long-acting injectable antipsychotics.
- To explore how variations in dopamine D2 receptor occupancy affect mental state during antipsychotic dosing cycles.
Main Methods:
- A longitudinal study tracking mental state changes within dosing cycles of depot flupentixol and zuclopenthixol.
- Utilized the Positive and Negative Syndrome Scale (PANSS) to monitor global mental state, stratified into five domains.
- Calculated striatal D2 occupancy based on plasma assays at peak and trough concentrations.
Main Results:
- Preliminary findings in ten participants indicate a correlation between global mental state decline and the rate of D2 occupancy reduction.
- Faster D2 occupancy reduction was associated with worsening of 'positive' and 'resistance' PANSS domains (p=0.047 and p=0.018, respectively).
- No significant relationship was found between PANSS score changes and the absolute reduction in D2 occupancy.
Conclusions:
- The observational study design is feasible and practical for this research area.
- A faster rate of D2 receptor occupancy reduction may elevate the risk of positive psychotic symptoms and irritability.
- Slower D2 occupancy reduction might mitigate these adverse effects; further research is needed for confirmation.
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