Clinical response in patients treated with once-monthly paliperidone palmitate: analysis of a therapeutic drug monitoring (TDM) database

To investigate pharmacokinetic correlates of clinical response in patients treated with once-monthly paliperidone palmitate (PP1M) injections at steady state. Plasma concentrations and dose-adjusted-plasma concentrations (C/D) of paliperidone from a naturalistic therapeutic drug monitoring (TDM) database were compared between responders and non-responders using the Clinical Global Impressions-Improvement scale (CGI-I) ratings. Analyses were based on the non-parametric Mann-Whitney U test and the Pearson Chi-squared test (χ²) with a significance level of 0.05. Subgroup analyses were performed separately in patients with schizophrenia spectrum, schizoaffective disorders and bipolar disorders. Comparing 93 responders with 80 non-responders, we detected no significant differences in the proportion of females, age, and body mass index (p's ranging 0.18-0.83); there were more smokers in the group of non-responders (p = 0.04), which also included more patients with bipolar disorders (p = 0.014). Despite the lack of differences for prescribed PP1M doses and dose intervals (p = 0.42 and p = 0.11, respectively), non-responders had higher paliperidone plasma concentrations and C/D levels (p = 0.033 and p = 0.021, respectively). Subgroup analyses did not yield differences for paliperidone plasma and C/D levels between non-responders and responders with schizophrenia spectrum (p = 0.099 and p = 0.14, respectively) and bipolar disorders (p = 0.95 and p = 0.75, respectively); dose-adjusted plasma concentrations were higher in non-responders compared to responders with schizoaffective disorders (p = 0.039), while no differences were reported for plasma levels (p = 0. 15). Our results show that paliperidone plasma concentrations over injection doses may be associated with patterns of clinical response suggesting potential utility of TDM as part of PP1M-based maintenance treatment.