Zuclopenthixol decanoate in pregnancy: Successful outcomes in two consecutive off springs of the same mother

Introduction. Almost all individual antipsychotics are classified into the intermediate pregnancy risk category as no or limited data exist about human pregnancy outcomes. We presented the case of zuclopenthixol decanoate using in two successive pregnancies of the same woman, which had not been published in the available peer-reviewed literature. Case report. A middle-age female subject who suffered from schizophrenia received zuclopenthixol decanoate injection during her two consecutive pregnancies. About four and a half months before diagnosis of the first pregnancy (~3.5 years after psychosis emergence), zuclopenthixol decanoate (400 mg every other week, im injection) was introduced to the treatment protocol (due to previous non-compliance with halo-peridol and risperidone). A significant clinical improvement was achieved and the dose during pregnancy was reduced to 200 mg once monthly and maintained to date. In both pregnancies the women gave birth to healthy girls who have been developing normally until now, at their ages of 6 months and of 3.5 years. During pregnancy and after giving birth to children the mothers' psychiatric status and her social functioning were significantly improved and are still stable. Close monitoring of the mother's health, a multidisciplinary approach to both her treatment and the monitoring of pregnancies as well as the complete compliance with the prescribed drug protocol were likely to be crucial for the therapeutic success. Conclusion. A favorable outcome of the present case suggests that the zuclopenthixol decanoate is a rational therapeutic option for pregnant women suffering from psychosis when the expected benefit exceed the potential risk, but a definitive evidence for its safety requires large, controlled studies

Long-term treatment with olanzapine in hospital conditions: Prevalence and predictors of the metabolic syndrome

© 2015, Serbia Medical Society. All rights reserved. Introduction The risk of metabolic abnormalities is greatly increased in schizophrenic patients started on an atypical antipsychotic medication. Patients with psychiatric disorders exceed mortality ranges resulting from, among others, increased risk of cardiovascular events. Other factors contributing to the development of metabolic syndrome include prolonged duration of illness, increasing age, female sex and lifestyle factors. Objective This cross-sectional study was taken up to assess the prevalence of the metabolic syndrome (MetS) in schizophrenic patients receiving olanzapine monotherapy for at least six months and to determine the most important risk factors associated with metabolic syndrome presence in these patients. Methods A total of 93 long term hospitalized schizophrenic patients (71 men, 22 women), had a screening of the following: case-history data, psychiatric scales, anthropometric measures, blood (fasting glucose, lipid status, C-reactive protein – CRP) and urine samples (microalbuminuria). Results Prevalence of MetS according to International Diabetes Federation criteria in our study was 34.4%. The multivariate analysis distinguished the following significant predictors of MetS presence (in order of appearance): data about diabetes mellitus in family history (p=0.002), body mass index >25 kg/m2 (p=0.002), hyperlipidemia in family history (p=0.008), and elevated CRP value (p=0.042). Conclusion High rate of MetS in patients treated with olanzapine in this study exceeds MetS prevalence in general population. Among observed parameters, our study pointed to several “high risk” predictors associated with MetS presence. Regular monitoring of cardiometabolic risk factors is highly recommended. Positive heredity distress mentioned above may direct a psychiatrist to prescribe some other drug than olanzapine in the long term treatment of schizophrenia

Risk factors for severe dental anxiety among medical students

Background/Aim. Severe dental anxiety (SDA) is the most severe form of dental anxiety, thus the aim of this study was to determine the factors associated with SDA in students of health-related disciplines. Methods. In this case-control study the cases were students with severe dental anxiety. The study was conducted at the Faculty of Medical Sciences, University of Kragujevac, Serbia. The participants were undergraduate students attending lectures during spring semester 2010/2011 (n = 1,812). A random sample of 800 students was assessed for the association between various risk factors and the severe dental anxiety. The main outcome measures were the data on demographics, dental anxiety, habits concerning oral hygiene, nutrition, general anxiety and (co)morbidity which were collected from the study participants by semi-structured question questionnaire. Results. Less frequent visits to the dentist (OR adjusted = 7.02 [2.65; 18.60]) and visiting the dentist only when there is a dental problem (OR adjusted = 8.08 [1.28; 50.93]) were associated with severe dental anxiety. The same was true for improper oral hygiene (OR adjusted = 4.25 [1.16; 15.60]). Factors as changing toothbrush more frequently (OR adjusted = 0.33 [0.14; 0.76]) and having chronic disease (OR adjusted = 0.01 [0.00; 0.09]) were inversely associated with severe dental anxiety. The level of education of students was not associated with severe dental anxiety. Conclusion. Inappropriate oral hygiene, less frequent changes of a toothbrush and less frequent visits to the dentist are important risk factors for severe dental anxiety

The influence of CYP2C8∗3 on carbamazepine serum concentration in epileptic pediatric patients

© 2016 Walter de Gruyter GmbH, Berlin/Boston. The aim of the present study was to investigate the distribution of CYP2C8 variants ∗3 and ∗5, as well as their effect on carbamazepine pharmacokinetic properties, in 40 epileptic pediatric patients on carbamazepine treatment. Genotyping was conducted using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and allele-specific (AS)-PCR methods, and steady-state carbamazepine plasma concentrations were determined by high performance liquid chromatography (HPLC). The CYP2C8 ∗3 and ∗5 polymorphisms were found at frequencies of 17.5 and 0.0%, respectively. After dose adjustment, there was a difference in daily dose in CYP2C8∗3 carriers compared to non carriers [mean ± standard deviation (SD): 14.19 ± 5.39 vs. 15.46 ± 4.35 mg/kg; p = 0.5]. Dose-normalized serum concentration of carbamazepine was higher in CYP2C8∗3 (mean ± SD: 0.54 ± 0.18 vs. 0.43 ± 0.11 mg/mL, p = 0.04), and the observed correlation between weight-adjusted carbamazepine dose and carbamazepine concentration after dose adjustment was significant only in CYP2C8∗3 non carriers (r = 0.52, p = 0.002). However, the population pharmacokinetic analysis failed to demonstrate any significant effect of CYP2C8 ∗3 polymorphism on carbamazepine clearance [CL L/h = 0.215 + 0.0696∗SEX+ 0.000183∗DD]. The results indicated that the CYP2C8∗3 polymorphism might not be of clinical importance for epilepsy treatment in pediatric populations

CYP3A5 polymorphism in serbian paediatric epileptic patients on carbamazepine treatment

© 2015 University of Kragujevac, Faculty of Science. All rights reserved. Carbamazepine exhibits significant inter-individual variability in its efficacy and safety, which leads to unpredictable therapy outcomes for the majority of patients. Although its complex biotransformation depends on CYP3A5 activity, evidence of association between carbamazepine treatment outcomes and CYP3A5 functional variations remains inconclusive. The aim of the present study was to investigate the distribution of two of the functionally important CYP3A5 variants *2 and *3 as well as their effects on carbamazepine dose requirements, plasma concentrations and clearance in a Serbian population. The study involved 40 paediatric epileptic patients on steady-state carbamazepine treatment. Geno-typing was conducted using the PCR-RFLP method, and carbamazepine plasma concentrations were determined using the HPLC method. CYP3A5*2 and *3 polymorphisms were found at frequencies of 0.0% and 97.5%, respectively, which corresponds well to previously published data for Caucasians. No differences in CYP3A5*3 allele frequencies were detected among epileptic patients in comparison to healthy volunteers within similar ethnic populations (p>0.08), indicating that CYP3A5 polymorphism does not represent a risk factor for epilepsy development. There was an observed tendency towards lower dosage requirements (mean±SD: 15.06±4.45 mg/kg vs. 18.74±5.55 mg/kg; p=0.26), higher plasma concentrations (mean±SD: 0.45±0.13 mg/kg vs. 0.38±0.03 mg/ kg; p=0.47) and lower clearance (mean±SD: 0.14±0.05 mg/ kg vs. 0.15±0.01 mg/kg; p=0.79) of carbamazepine in homozygous carriers of CYP3A5*3/*3 compared to heterozygous CYP3A5*1A/*3 Serbians. Because these genotype groups did not differ significantly in terms of their carbamazepine pharmacokinetics parameters, the proposed effects of CYP3A5*3 on carbamazepine metabolism could not be confirmed

Population pharmacokinetic of antiepileptic drugs in different populations

This article reviews a population pharmacokinetics studies conducted during the past few years in Serbia. Studies have included three the most frequently used antiepileptic drugs (valproate, carbamazepine and lamotrigine) and different populations of epileptic patients: children, adults and heterogeneous population composed of both children and adults. The review compares obtained values of population pharmacokinetic models of clearance of these drugs, and factors that are significantly determined, making brief comments on the results of other authors on the same topic. Individualization of drug dosage is the basis of rational therapy, and factors of variability will always be subject of scientific research. © 2013 Versita Warsaw and Springer-Verlag Berlin Heidelberg

CYP3A5 Polymorphism In Serbian Paediatric Epileptic Patients On Carbamazepine Treatment

Carbamazepine exhibits significant inter-individual variability in its efficacy and safety, which leads to unpredictable therapy outcomes for the majority of patients. Although its complex biotransformation depends on CYP3A5 activity, evidence of association between carbamazepine treatment outcomes and CYP3A5 functional variations remains inconclusive. The aim of the present study was to investigate the distribution of two of the functionally important CYP3A5 variants *2 and *3 as well as their effects on carbamazepine dose requirements, plasma concentrations and clearance in a Serbian population. The study involved 40 paediatric epileptic patients on steady-state carbamazepine treatment. Genotyping was conducted using the PCR-RFLP method, and carbamazepine plasma concentrations were determined using the HPLC method. CYP3A5*2 and *3 polymorphisms were found at frequencies of 0.0% and 97.5%, respectively, which corresponds well to previously published data for Caucasians. No differences in CYP3A5*3 allele frequencies were detected among epileptic patients in comparison to healthy volunteers within similar ethnic populations (p>0.08), indicating that CYP3A5 polymorphism does not represent a risk factor for epilepsy development. There was an observed tendency towards lower dosage requirements (mean±SD: 15.06±4.45 mg/kg vs. 18.74±5.55 mg/kg; p=0.26), higher plasma concentrations (mean±SD: 0.45±0.13 mg/kg vs. 0.38±0.03 mg/kg; p=0.47) and lower clearance (mean±SD: 0.14±0.05 mg/kg vs. 0.15±0.01 mg/kg; p=0.79) of carbamazepine in homozygous carriers of CYP3A5*3/*3 compared to heterozygous CYP3A5*1A/*3 Serbians. Because these genotype groups did not differ significantly in terms of their carbamazepine pharmacokinetics parameters, the proposed effects of CYP3A5*3 on carbamazepine metabolism could not be confirmed

Foreign Direct Investments as a Source of Financing of Economic Development of Western Balkan Countries

The paper considers economic growth of five Western Balkan countries on the one hand, and on the other the affluence of direct foreign investments as one of external sources of growth in the period 2000-2017. The starting point was the attitude that due to insufficient domestic savings and engagement of foreign investments, those countries have to treat external sources of investment as a condition of permanent change of economic growth rate to a higher level, because it is obvious that after the economic crisis in 2009, the economic growth rates do not provide closure of developmental gap with EU countries. Therefore, foreign direct investments are the supplement to domestic accumulation. However, without disclaiming their benefits, it should be borne in mind that they cannot be substitution for domestic saving