Therapeutic drug monitoring of patients on risperidone depot

Risperidone depot is the first long-acting atypical antipsychotic to be registered in Norway. The combination of antipsychotic efficacy for negative symptoms, reduction of adverse effects and assured delivery of medication is expected to improve patient compliance and thus reduce the rate of hospitalization. Nevertheless, clinicians have reported that risperidone depot has shown poor antipsychotic response in a number of patients. We therefore performed a retrospective, naturalistic study in search of a pharmacokinetic explanation for this reported lack of response. The study is based on data from therapeutic drug monitoring (TDM) of 46 patients on risperidone depot and 50 patients on oral risperidone. There was a significantly lower mean total serum drug level of risperidone and its active metabolite 9-OH risperidone among patients receiving standard doses of risperidone depot (25-50 mg/14 days) compared with patients on oral risperidone (2-6 mg/day). About 25% of patients receiving risperidone depot showed total serum drug levels below established reference range (30-120 nmol/l), even when steady state was presumed. In contrast, only 6% of patients on oral risperidone had a total serum drug level under this reference range. There was a wide range in total serum drug levels among patients in both groups. Explanations for these findings may be skewed selection of patients, flaws in the injection procedure, or unpredictable absorption of the active moiety from injection site. There is, however, only a presumed relationship between serum drug level and antipsychotic efficacy for risperidone.