Risperidone Serum Levels in Depression: Insights From a Retrospective Therapeutic Drug Monitoring Study

BACKGROUND: Risperidone is used as an adjunctive treatment for treatment-resistant depression, yet the therapeutic drug monitoring guidelines only include therapeutic reference ranges for schizophrenia. No therapeutic reference range for risperidone has been established for depressive disorders. METHODS: We performed a retrospective observational study involving inpatients who were administered risperidone from 2015 to 2020. Serum concentrations of the active moiety (AM) of risperidone (risperidone and its main metabolite 9-hydroxyrisperidone) were compared between patients suffering from schizophrenia spectrum disorders (SSD) and depression, as well as between nonpsychotic and psychotic depressive patients. In the depression cohort, associations between AM serum levels and treatment efficacy were assessed using the Clinical Global Impression-Improvement scale. RESULTS: In total, 401 inpatients were included; of which, 220 were diagnosed with depressive disorders (ICD-10: F32/F33), consisting of 40 with psychotic features, and 181 with SSD. AM serum concentration was significantly higher in patients with SSD compared with those with depression with or without psychotic symptoms (P < 0.001). In total, 50% of the patients with depressive disorders with or without psychotic features were successfully treated with lower doses and serum concentrations than those administered to patients with SSD. CONCLUSIONS: Therapeutic reference ranges established for SSD cannot be applied to the treatment of depressive disorders. According to the recommendation rules of the therapeutic drug monitoring Task Force of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie, we suggest a preliminary therapeutic reference range of 10-30 ng/mL (recommendation level 3) for risperidone as a treatment for depressive disorders.