Clinical Correlates of Antipsychotic Plasma Levels with Long-Acting Paliperidone: Corrélats cliniques des concentrations plasmiques de palipéridone à libération prolongée.

Objectives: The majority of patients with schizophrenia experience dramatic improvement in psychotic symptoms when treated with antipsychotic medication. Maintenance treatment can prevent relapses but problems with medication adherence limit effectiveness. Long-acting injectable antipsychotics (LAIs) provide an opportunity to establish adherence but challenges remain in ensuring that the dose selected is therapeutic. Therapeutic drug monitoring has not been established as valuable for LAIs in the maintenance treatment of schizophrenia. This exploratory study was undertaken to describe plasma paliperidone levels in outpatients treated with the LAI paliperidone palmitate and to determine whether paliperidone levels are associated with subjective experience on medication and side effects.

Methods: Twenty-one outpatients with schizophrenia receiving treatment with LAI paliperidone consented to participation in this study. Blood samples were obtained for measurement of paliperidone and prolactin levels at the first visit. A second paliperidone level was obtained at the time of the next injection for 18 of the participants. Clinical rating scales were administered at the first visit to assess illness severity, attitudes regarding medication, subjective well-being and side effects.

Results: Paliperidone levels were highly correlated at the two time points (ρ = .85;  < .001). Mean paliperidone level at the first visit was 34.9 ng/ml and ranged from 5.1 to 73.9 ng/ml. Higher paliperidone levels were correlated with higher prolactin levels (ρ = 0.59,  < .01) and lower sexual desire (ρ = -.58,  < .01).

Conclusions: We demonstrated that paliperidone levels can be measured reliably in patients receiving LAI paliperidone. Higher plasma levels were associated with higher prolactin levels and reduced sexual desire but not with measures of subjective experience on medications or other side effects. Measurement of paliperidone levels in patients treated with paliperidone palmitate may have the potential to minimize the dose of medication prescribed and, in turn, the severity of sexual side effects.