Correlations between receptor occupancy change and mental state in patients using long-acting injectable antipsychotics: MIDILIA pilot study.

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.