Computational protocol: Application of Plasma Levels of Olanzapine and N-Desmethyl-Olanzapine to Monitor Clinical Efficacy in Patients with Schizophrenia

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Protocol publication

[…] This study used modified high-performance liquid chromatography (HPLC) coupled with electrochemical detector as described in our previous study [], except that 80 mM phosphate buffer (NaH2PO4) was used to enhance system stability and LC-MS-grade acetonitrile was used to minimize noise. Patients meeting the inclusion criteria (aged 18–60 years, stable OLZ dose for at least three months, and full capacity to consent) were recruited according to the methodology of Lu et al. []. This study, including its procedures, was approved by the institutional review board and the ethics committee of Taipei Medical University (Approval No. F950206), and all clinical investigations were conducted according to the principles expressed in the Declaration of Helsinki. The participants were included in the study only if they had full capacity by themselves to provide written consent to participate in the study. The understanding of the patients of all procedures and their capacity to provide consent was assessed by direct examination of the participants by a clinician experienced in the evaluation of mental illness. Patients with addictions and who were pregnant, lactating, or had disease conditions that might interfere with monitoring were excluded. Samples from patients prescribed medications with evidence for interactions with OLZ were excluded. Samples were drawn in the morning approximately 12 hours after the last dose of OLZ and analyzed to determine COLZ and CDMO.During the study period, the symptom severity of the recruited patients was also routinely assessed by a psychiatric physician using the Positive and Negative Syndrome Scale (PANSS). PANSS is clinically used to assess schizophrenic symptoms, including positive, negative and general psychopathology scales []. The clinical efficacy of olanzapine was determined using the PANSS [,]. PANSS scores ≤58 were defined as mildly ill, as established by Leucht and coworkers[].Descriptive statistics are presented as the mean ± standard deviation (SD). The drug concentration normalized by the administered dose is expressed as the C/D ratio. Recruited patients were subgrouped by smoking status and sex, which are known to influence variations of OLZ levels. Intergroup comparisons were performed by Mann-Whitney U test. To quantify the ability of drug-level indicators (COLZ, CDMO or ratio of COLZ/CDMO) to identify schizophrenic symptomatic status in terms of various PANSS scores, Spearman’s rank order correlation method (rs) analysis was conducted using SigmaPlot 12.0. The false discovery rate (FDR) was applied for multiple testing corrections []. To determine the cut-off values to indicate that the patients’ clinical symptoms were maintained at an at least mildly ill status (PANSS total score ≤58) [], the ROC curve was plotted using SPSS 20, and the area under the curve (AUC) was used for accuracy comparison. The indicators with the highest sensitivity and specificity were considered the thresholds for each test. A p value <0.05 was considered significant. […]

Pipeline specifications

Software tools SigmaPlot, SPSS
Application Miscellaneous
Organisms Homo sapiens