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Michaela Mayerova,1–3 Libor Ustohal,1–3 Jiri Jarkovsky,4 Jan Pivnicka,1,5 Tomas Kasparek,1,2 Eva Ceskova1,3 1Faculty of Medicine, Masaryk University, Brno, Czech Republic; 2Department of Psychiatry, University Hospital Brno, Brno, Czech Republic; 3CEITEC – Central European Institute of Technology, Masaryk University, Brno, Czech Republic; 4Institute of Biostatistics and Analyses, Masaryk University, Brno, Czech Republic; 5Institute of Forensic Medicine, St. Anne’s University Hospital, Masaryk University, Brno, Czech Republic Introduction: Therapeutic drug monitoring (TDM) of clozapine is a very useful method for verifying both the correct intake and the interindividual variability of its metabolism, thereby avoiding the risk of toxicity. The purposes of this paper were to discover how many patients using clozapine in common clinical practice have clozapine plasma concentration (PC) levels in the proposed reference range and to identify factors that influence clozapine PC levels. Methods: Our study included 100 inpatients (diagnosed with schizophrenia or schizoaffective disorder) taking standard doses of clozapine (100–700 mg/day). Clozapine concentration was measured by high-performance liquid chromatography. Correlations between doses and PC levels and the influence of smoking and gender on clozapine PC levels were calculated. Results: A large number of the patients (67%) had PC levels outside the proposed reference range. The clozapine PC levels were influenced by dose, gender, and cigarette smoking. Conclusion: The correlations between dose, gender, and cigarette smoking and clozapine PC levels highlighted by our study overlap other research. It was surprising to find such a large number of patients with clozapine PC levels outside the therapeutic range. This result suggests the importance of clozapine TDM due to misunderstood inter- and/or intraindividual variability or misestimated partial therapeutic compliance. Keywords: therapeutic drug monitoring, plasma levels, interindividual variability, schizophrenia, schizoaffective disorder

Mayerova M, Ustohal L, Jarkovsky J, et al. Neuropsychiatr Dis Treat. 2018;14:1535–1543. On page 1539, “Clozapine doses and clozapine PCs” section, second paragraph, line 2, the following sentence was incorrect: “The clozapine PC levels of 67% of patients were outside the proposed reference range (proposed reference range 350–600 ng/mL);28 the levels of 43% were above and 24% of patients had levels below the proposed reference range.” The correct sentence is: “The clozapine PC levels of approximately67% of patients were outside the proposed reference range (proposed reference range 350–600 ng/mL);7 42% of patients had levels below and 25% of patients had levels above the proposed reference range.”On page 1541, “Discussion” section, first paragraph, line 2, the following sentence was incorrect: “In contrast to the study by Couchman, in which more PC levels were below the proposed reference range (42.5% under and 28.4% above), in our study more PC levels were above (43% above and 24% under).”The correct sentence is: “In agreement with the study by Couchman, in which more PC levels were below the proposed reference range (42.5% below and 28.4% above), our study also found more PC levels below (42% below and 25% above).” Read the original article

Competing Interests: The authors have no conflicts of interest or financial disclosures to report.

Objective: Patients with schizophrenia are at higher risk of cardiovascular (CVS) related mortality. Close attention is being paid to the clinical utility of readily available CVS markers., Methods: A pilot one-year longitudinal study in inpatients with first-episode psychosis (FEP) was carried out to determine markers of inflammation and endothelial dysfunction (monocyte- and neutrophil-to-lymphocyte ratios) and basal blood pressure, pulse, and derived hemodynamic parameters (PP: pulse pressure; RPP: rate pressure product; and MAP: mean arterial pressure)., Results: After one year, PP and RPP increased, as did systolic blood pressure and heart rate. Systolic blood pressure, PP, total white blood cells, and neutrophils correlated with weight gain. After one year, correlations between monocyte-to-lymphocyte ratio and RPP and MAP were observed., Conclusion: Our study indicates worsening CVS health over the first year of treatment and emphasises the importance of early monitoring of CVS status using easily accessible parameters to prevent CVS-related mortality.Key pointsPatients with schizophrenia are at higher risk of cardiovascular mortality.The CVS risk could be evaluated using affordable, routinely available CVS markers such as monocyte- and neutrophil-to-lymphocyte ratios, blood pressure, and pulse together with the derived parameters.Our pilot study in first-episode psychosis patients indicates worsening of CVS health based on these parameters during the first year of treatment, the early monitoring of CVS status is highly relevant in clinical practice.

Objectives: Schizophrenia is accompanied by impaired cortical inhibition, as measured by several markers including the cortical silent period (CSP). It is thought that CSP measures gamma-aminobutyric acid receptors B (GABA B ) mediated inhibitory activity. But the mutual roles of schizophrenia as a disease and the drugs used for the treatment of psychosis on GABA mediated neurotransmission are not clear., Methods: We recruited 13 drug-naive patients with first-episode schizophrenia. We used transcranial magnetic stimulation to assess CSP prior to initiating risperidone monotherapy and again four weeks later. At the same time, we rated the severity of psychopathology using the Positive and Negative Syndrome Scale (PANSS)., Results: We obtained data from 12 patients who showed a significant increase in CSP, from 134.20±41.81 ms to 162.95±61.98 ms ( p=0.041; Cohen's d=0.544). After the treatment, the PANSS total score was significantly lower, as were the individual subscores ( p<0.05). However, no correlation was found between ΔCSP and ΔPANSS., Conclusion: Our study in patients with first-episode schizophrenia demonstrated an association between risperidone monotherapy and an increase in GABA B mediated inhibitory neurotransmission.