Long-acting injectable risperidone and metabolic ratio: A possible index of clinical outcome in treatment-resistant schizophrenic patients

Rationale: It is still common to encounter a partial or no response to antipsychotic treatment in clinical practice, but only individual case reports are currently available concerning the efficacy of long-acting risperidone (RLAI) in treatmentresistant schizophrenia. The relationship between RSP and 9-OH-RSP plasma levels, and clinical response or tolerability has not yet been thoroughly assessed. Methods This open-label, non-randomised study involved 30 outpatients with treatment-resistant schizophrenia, who were prescribed RLAI for 6 months, and clinically evaluated using the Brief Psychiatric Rating Scale (BPRS), the Positive and Negative Symptoms Scale (PANSS), the Clinical Global Impression-Improvement Scale (CGI-I), and the Simpson and Angus Scale for Extrapyramidal Side Effects (EPSE). Plasma RSP and 9-OH-RSP levels were determined at steady-state, and the metabolic ratio (MR) was calculated as plasma 9-OH-RSP/RSP levels. Results At the end of the study, 60% of the patients responded to RLAI (a ≥20% reduction in the PANSS score). Linear regression analysis showed a significant positive relationship between the RSP dose and active moiety (RSP+9-OH-RSP) (r=0.4; p=0.02). There was a significant positive relationship between active moiety and EPSE scores (r=0.6; p=0.00). The BPRS responders had a significantly higher mean MR than the non-responders (3.41±1.87 SD vs 1.60±0.98 SD) (p=0.00). Conclusions Therapeutic drug monitoring seems to be useful in optimising the dose of RLAI, especially in the case of tolerability problems. MR might be a better index of clinical response to RLAI than the value of the active moiety, although this needs to be confirmed by further data.