Risperidone in schizophrenia: is there a role for therapeutic drug monitoring?

Although risperidone is commonly used in the acute and maintenance treatment of schizophrenia, the role of therapeutic drug monitoring has yet to be elucidated. The purpose of this review was to determine whether risperidone warrants therapeutic drug monitoring in patients with schizophrenia. Using a previously published nine-step decision-making algorithm, the available evidence was examined to determine whether therapeutic drug monitoring of risperidone is warranted in adult schizophrenic patients. Analytical methods used to quantify risperidone, 9-hydroxyrisperidone, and the combined active moiety are specific, sensitive, accurate, and precise; however, the therapeutic range for risperidone has not yet been established. Relationships between risperidone dose and plasma concentrations of risperidone, 9-hydroxyrisperidone, or the active moiety have not yet been demonstrated. A clear correlation between plasma risperidone concentrations and therapeutic response has also not been shown. Intrinsic interpatient variability, genetically based differences in drug metabolism, and metabolic drug interactions may all influence the variability in plasma concentrations. Patients with schizophrenia on risperidone for prevention of relapse take the medication for a sufficient duration of therapy to benefit from therapeutic drug monitoring; however, the routine use of risperidone concentrations in all patients with schizophrenia is not likely to have a significant impact on the clinical decision-making process or provide more information than clinical judgment alone. The routine use of risperidone levels does not seem warranted in all patients with schizophrenia. Clinical end points (ie, response and toxicity) should be monitored by assessing changes in symptoms and emergence of adverse effects, especially extrapyramidal symptoms. Therapeutic drug monitoring of risperidone may be beneficial in certain circumstances, including assessing potential noncompliance and supporting compliance, ruling out therapeutic failure as a result of low drug concentrations, and identifying and managing drug interactions, adverse effects, and use in special populations.