Risperidone in Schizophrenia: Is There a Role for Therapeutic Drug Monitoring?

Abstract

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.

Predicting Plasma Concentration of Risperidone Associated With Dosage Change

“…Therefore, the studies that presented negative results should not be interpreted in the same manner as for those with positive ones. 22 The results of our study must be interpreted in light of limitations. First, although the predictive performance was assessed with the mean prediction error and the root mean squared prediction error, 13 there was no other model to compare the results with.…”

“…20,21 These inconsistent findings seem to stem from small sample sizes, as a recent systematic review has pointed out. 22 Furthermore, these data originate from clinical trials that have methodological issues, such as open-label or naturalistic study design, which indicates a possibility that doses of risperidone would have been increased in nonresponders. 22 When doses are increased in nonresponders, a true concentration-effect relationship can easily be made complex to interpret because true nonresponders would then present with higher concentrations than responders.…”

“…22 Furthermore, these data originate from clinical trials that have methodological issues, such as open-label or naturalistic study design, which indicates a possibility that doses of risperidone would have been increased in nonresponders. 22 When doses are increased in nonresponders, a true concentration-effect relationship can easily be made complex to interpret because true nonresponders would then present with higher concentrations than responders. Therefore, the studies that presented negative results should not be interpreted in the same manner as for those with positive ones.…”

Therapeutic Drug Monitoring of Common Antipsychotics

“…Several LC-MS/MS methods for analysis of quetiapine alone or in combination with other neuroleptics have been described. 59,66,[170][171][172][173] Risperidone is a so-called highpotency antipsychotic because at low doses of 2-6 mg/day it can achieve a good antipsychotic effect. It is approved for short-term and longterm treatment of schizophrenia and the acute maniac phase of bipolar disorder in adults and children.…”

Therapeutic drug monitoring of atypical antipsychotic drugs

“…The overall pharmacological effects of risperidone depend on the sum of plasma concentrations of risperidone and its 9-OH-RSP metabolite (total active moiety), so monitoring plasma concentrations of the parent compound (risperidone) alone can lead to erroneous interpretations. Therapeutic drug monitoring of risperidone may be beneficial in certain circumstances, including assessing potential non-adherence and supporting adherence, ruling out therapeutic failure as a result of low drug concentrations, and identifying and managing drug interactions, adverse effects, and use in special populations (39). Moreover, risperidone TDM should be particularly useful when medication is switched from the oral to injectable depot form or vice versa (15).…”