Dried Blood Spot Analysis for Therapeutic Drug Monitoring of Antipsychotics: Drawbacks of Its Clinical Application. Issue 3 (June 2018) - Kloosterboer, Sanne M.
Abstract : Background: Dried blood spot (DBS) sampling offers a minimally invasive sampling method for therapeutic drug monitoring of antipsychotics. To facilitate implementation in clinical practice, the aim of this study was to perform a clinical validation study of a DBS method for quantification of risperidone, aripiprazole, pipamperone, and their major metabolites 9-OH risperidone and dehydro-aripiprazole in a real-life, clinical setting. Methods: Paired DBS and venous plasma samples were analyzed (n = 35 for risperidone, n = 21 for aripiprazole, n = 21 for pipamperone). Estimated plasma concentrations were calculated from DBS concentrations based on hematocrit and/or Deming regression formulas. Deming regression and Bland–Altman analyses were used to determine the agreement between the calculated and measured plasma concentrations. For Bland–Altman analysis, the following acceptance limit was used: for a minimum of 67% of the samples, the difference of the 2 measurements should be within 20% of their mean. Results: The median venous plasma levels were 0.9 mcg/L for risperidone, 14.8 mcg/L for 9-OH risperidone, 135.4 mcg/L for aripiprazole, 54.9 mcg/L for dehydro-aripiprazole, and 56.4 mcg/L for pipamperone. All antipsychotics required different correction formulas of DBS concentrations for best agreement. Subsequently, no constant or proportional bias was observed using Deming regression analysis. With Bland–Altman analyses, for risperidone, 45% of the samples were within the 20% limits; for 9-OH risperidone, 36%; for aripiprazole, 45%; for dehydro-aripiprazole, 35%; and for pipamperone, 43%. Conclusions: The DBS method to quantify risperidone, aripiprazole, pipamperone, and their major metabolites did not meet the acceptance criteria in the Bland–Altman analyses. Therefore, this DBS method was not clinically valid. This study shows the importance of a clinical validation study with use of Bland–Altman plots before clinical implementation.