Browsing by Author "Pavlović, Zorana (24831071100)"

Importance: Precise estimation of the drug metabolism capacity for individual patients is crucial for adequate dose personalization. Objective: To quantify the difference in the antipsychotic and antidepressant exposure among patients with genetically associated CYP2C19 and CYP2D6 poor (PM), intermediate (IM), and normal (NM) metabolizers. Data Sources: PubMed, Clinicaltrialsregister.eu, ClinicalTrials.gov, International Clinical Trials Registry Platform, and CENTRAL databases were screened for studies from January 1, 1990, to June 30, 2020, with no language restrictions. Study Selection: Two independent reviewers performed study screening and assessed the following inclusion criteria: (1) appropriate CYP2C19 or CYP2D6 genotyping was performed, (2) genotype-based classification into CYP2C19 or CYP2D6 NM, IM, and PM categories was possible, and (3) 3 patients per metabolizer category were available. Data Extraction and Synthesis: The Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines were followed for extracting data and quality, validity, and risk of bias assessments. A fixed-effects model was used for pooling the effect sizes of the included studies. Main Outcomes and Measures: Drug exposure was measured as (1) dose-normalized area under the plasma level (time) curve, (2) dose-normalized steady-state plasma level, or (3) reciprocal apparent total drug clearance. The ratio of means (RoM) was calculated by dividing the mean drug exposure for PM, IM, or pooled PM plus IM categories by the mean drug exposure for the NM category. Results: Based on the data derived from 94 unique studies and 8379 unique individuals, the most profound differences were observed in the patients treated with aripiprazole (CYP2D6 PM plus IM vs NM RoM, 1.48; 95% CI, 1.41-1.57; 12 studies; 1038 patients), haloperidol lactate (CYP2D6 PM vs NM RoM, 1.68; 95% CI, 1.40-2.02; 9 studies; 423 patients), risperidone (CYP2D6 PM plus IM vs NM RoM, 1.36; 95% CI, 1.28-1.44; 23 studies; 1492 patients), escitalopram oxalate (CYP2C19 PM vs NM, RoM, 2.63; 95% CI, 2.40-2.89; 4 studies; 1262 patients), and sertraline hydrochloride (CYP2C19 IM vs NM RoM, 1.38; 95% CI, 1.27-1.51; 3 studies; 917 patients). Exposure differences were also observed for clozapine, quetiapine fumarate, amitriptyline hydrochloride, mirtazapine, nortriptyline hydrochloride, fluoxetine hydrochloride, fluvoxamine maleate, paroxetine hydrochloride, and venlafaxine hydrochloride; however, these differences were marginal, ambiguous, or based on less than 3 independent studies. Conclusions and Relevance: In this systematic review and meta-analysis, the association between CYP2C19/CYP2D6 genotype and drug levels of several psychiatric drugs was quantified with sufficient precision as to be useful as a scientific foundation for CYP2D6/CYP2C19 genotype-based dosing recommendations.. © 2021 American Medical Association. All rights reserved.

Objective: To prospectively evaluate depressive symptoms and risk factors for depression in patients with chronic hepatitis C (CHC) treated with pegylated interferon alpha therapy combined with oral ribavirin (PEG-IFN-α+RBV) and to analyze self-rating scale for depression in comparison to observer-based scale in the given population. Subjects and methods: The Hamilton Depression Rating Scale and Zung Self Rating Depression Scale were used to screen for depressive symptoms in 74 subjects with CHC before PEG- IFN-α (mean dose 152.6±25.6 mcg), and in the follow-up visits (4, 12 and 24 week). Results: Incidence of depressive symptoms in patients (mean age 39.9±13.4 years; equal sex distribution p=0.225) treated by PEG- IFN-α was the highest on 12th week of the treatment, when more than a 20% of our sample had moderate/severe symptoms of depression, and about 30% had minor depressive symptoms. For the screening of depression during PEG- IFN-α self-assessment scale was equally reliable as observer-based assesment of depressive symptoms. Common clinical parameters- subject related risk factors (age (p=0.955 ), sex (p=0.008), lifetime psychiatric disorder (p=0.656)), illness related risk factors (duration of CHC (p=0.267), i.v drug aplication as way of transmission (p=0.292)) and therapy-related risk factors (recommended duration of PEG-IFN-α (p=0.993) and dose of PEG-IFN-α (p=0.841)) were not significantly associated with depressive symptoms on PEG-IFN-α. Conclusions: Liason-consultation services should collaborate with hepatologists in creating screening programmes, supplemented by objective criteria and guidelines, for early recognition and treatment of interferon-induced depression. © Medicinska naklada.

Background/Aim. Antidepressants are a widely used class of drugs. The aim of this study was to investigate different aspects of antidepressant prescribing practice at University Psychiatric Clinic in Belgrade. Methods. This cross-sectional study was carried out by retrospective analysis of the patient's medical charts. The study included all patients with antidepressant prescribed at discharge during 2009 (n = 296). The evaluation was focused on patient- related factors (socio-demographic and illness related), psychiatrist-related factors (sex and duration of working experience) and drug related factors (type of antidepressant, dose, polypharmacy and reimbursement by national health insurance). Results. Antidepressants were prescribed for unipolar depression (F32-34, ICD X) either without comorbidity (46.2%) or with comorbidity (24.7%), mostly as a monotherapy (91% had one antidepressant), to the patients who were 65% female, aged 50.1 ± 8.9, most of them with 12 years of education (52.6%), married (69.3%) and employed (55.9%). The majority of patients had a history of two hospitalizations (Med 2; 25th-75th perc. 1-4) during nine years (Med 9; 25th-75th perc. 2-15) after the first episode of depression. Among them, 19% were found to be suicidal in a lifetime. The single most prescribed antidepressant was sertraline (20.4%), followed by fluoxetine (13.3%) and maprotiline (11.7%). Utilization of antidepressants was positively correlated with the rate of reimbursement (p < 0.01). The most prescribed antidepressant group was selective serotonin reuptake inhibitors (SSRI) (47.8%), followed by tricyclic antidepresants (TCA) (25.3%) and new antidepressants - venlafaxine, tianeptine, mirtazapine, bupropion, trazodone (15.1%). Most of the drugs were prescribed in doses which are at the lower end of the recommended dose-range. Regarding severity of the actual depressive episode, TCA were prescribed for severe depression with psychotic features, while SSRI were choice for episodes with moderate symptom severity (p = 0.01). Psychiatrists with longer working age (20-30 years) hesitated to prescribe new antidepressants in comparison to younger colleagues (p = 0.01). Conclusion. Economic issues in Serbia as developing country influence the choice of antidepressants, as well as a psychiatrist's working age and severity of depression. However, SSRI are the drugs of the first choice, as it was shown in most of the developed countries nowadays.

Introduction Alcoholism is one of the most frequent modern diseases. These kinds of epidemiological studies have not been carried out in this country at a global level. Objective The aim of the study was to establish the spread of alcohol abuse among the young regarding the sex, and find the connection between the alcohol abuse and the consumption of drugs and cigarettes. Methods The study was carried out among the elementary school pupils of the seventh and eighth grade in the area of Belgrade from October 2003 to January 2004. Total of 457 pupils were involved; 229 (50.1%) were boys and 228 (49.9%) girls, aged 12-15 years, the average age being 13.4 years. The method used was the modified questionnaire European School Survey Project on Alcohol and Other Drugs, which the pupils filled in individually, voluntarily and anonymously. χ2-test, Student's t-test, Mann-Whitney Logistic Regression Test were used in statistical processing of the data. Results Almost 70% of the examinees have tried alcohol. Most of the examinees had the first contact with alcohol at the age of 11. Half of our examinees got drunk at least once in their life and about one fifth more than 20 times. The binge form of consumption (five or more drinks in a row) was evident in a quarter of our examinees. Our examinees use alcohol together with other psychoactive substances, mostly marijuana. It was observed that certain types of behaviour, such as frequent going out in the evening, were directly related to the abuse of alcohol. Conclusion Two thirds of the examinees have tried alcohol. The first contact with alcohol is shifted to an earlier age (11 years). New trends of alcohol abuse have been noticed, such as binge form of consumption and the connection of use with other psychoactive substances.

Introduction: Prescribing trends in maintenance therapy of patients with primary psychotic disorders (PSD) may vary worldwide. Present study aimed to investigate prescription patterns in a sample of outpatients with PSD from Serbia. Methods: In a sample of 73 PSD outpatients we analysed the rate of antipsychotic polypharmacy and psychotropic polypharmacy, concomitant continual benzodiazepine use, and associations between therapy, psychotic symptoms and quality of life. Results: Maintenance therapy (median daily dose 321 mg of chlorpromazine equivalents) predominantly consisted of monotherapy with second generation antipsychotics (45.2%), followed by antipsychotic polypharmacy based on first and second generation combination (25.0%). The median number of psychotropic drugs was 3. Benzodiazepines were continually prescribed to more than 60% of patients (mean daily dose 2.9 ± 2.0 mg lorazepam equivalents). Patients with benzodiazepine use had significantly more psychotropic medications and more antipsychotic polypharmacy, poorer quality of life and more severe psychopathology in comparison to another group. Conclusion: The present study demonstrated new information regarding the prescription patterns of psychotropic drugs in outpatients with PSD in Serbia, amplified with clinically relevant information. This study also revealed distinct prescription patterns concerning antipsychotic/benzodiazepine polypharmacy. Overall, such findings are likely to contribute to improving clinical practice and care for patients with PSD in general.Keypoints Present exploratory research aimed to elucidate trends of antipsychotics polypharmacy and concomitant use of psychotropic medications including benzodiazepines in the maintenance treatment of outpatients with schizophrenia and other psychotic disorders, amplified with clinically relevant information (symptoms and quality of life). ‘Antipsychotic (AP) polypharmacy’ was defined as concurrent use of more than one AP for at least 1 month; ‘Psychotropic polypharmacy’ was defined as the combination of AP and a different class of psychotropic drugs medication for at least one month. The median number of prescribed psychotropic drugs was 3 (mean 3.1 ± 1.1) and the average AP daily dose was moderate (median 321 mg of chlorpromazine equivalents). However, the rates of AP polypharmacy (45.2%) and benzodiazepine prescription on a continual basis ('60%) found in our sample could be considered relatively high. Outpatients with higher AP daily dose and higher BPRS symptom score were receiving more benzodiazepines. For improvement of the local, as well as general clinical practice and care for patients with psychotic disorders, and for education in psychiatry, such analyses need to be done on a regular basis and on larger samples. © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

Introduction: Studies consistently link excessive smartphone use to poor sleep quality, depression, anxiety, and stress. This study specifically aimed to investigate these associations among medical students in Belgrade and Nis (Central Serbia). Materials and methods: The cross-sectional study included a sample of 761 students, who were selected from both the Faculties of Medicine at the University of Belgrade and the University of Nis. Questionnaires, including the International Physical Activity Questionnaire – Short Form (IPAQ-SF), Smartphone Addiction Scale – Short Version (SAS-SV), the Pittsburgh Sleep Quality Index (PSQI), and the Depression, Anxiety, and Stress Scale – 21 items (DASS-21), were completed by the participants. Statistical analysis techniques, such as the Chi-square test, student’s t-test, and logistic regression, were employed to examine the relationship between smartphone addiction, physical activity, sleep quality, depression, anxiety, and stress. Results: The findings indicated a prevalence of smartphone addiction among medical students at 21.7%, with rates of 22.9% among males and 21.1% among females. Females exhibited significantly higher scores on the SAS-SV scale compared to males (p = 0.032). Univariate logistic regression analysis revealed significant associations between smartphone addiction and spending over 4 h daily on smartphones (OR = 2.39; p < 0.001), poor sleep quality (OR = 1.65; p = 0,005), as well as elevated levels of stress (OR = 1.75; p = 0.003), anxiety (OR = 2.04; p < 0.001), and depression (OR = 2.29; p < 0.001). Multivariate regression analysis identified spending more than 4 h daily on smartphones (OR = 2.39; p < 0.001) and increased levels of depression (OR = 2.51; p < 0.001) as independent significant factors associated with smartphone addiction. Conclusion: This study sheds light on the prevalence of smartphone addiction among medical students, with spending excessive time on smartphones and higher levels of depression standing out as significant factors. Future research should delve into the underlying mechanisms and causal relationships between smartphone addiction and these psychosocial factors. Understanding these connections will aid in developing effective interventions and strategies to tackle this growing public health concern. Copyright © 2023 Nikolic, Bukurov, Kocic, Vukovic, Ladjevic, Vrhovac, Pavlović, Grujicic, Kisic and Sipetic.

The introduction of antipsychotic medication in the 1950s forever changed the outlook on the treatment of schizophrenia, although there is still a large proportion of patients who do not reach functional recovery. At least 30% of patients do not respond to clozapine, the tricyclic dibenzodiazepine with complex pharmacological actions, which was proven to be more effective than any other antipsychotic in the treatment of schizophrenia. According to most of the therapeutic guidelines for schizophrenia, clozapine is the third line therapy for patients who did not respond to other antipsychotics. Large inter-individual variability exists for clozapine bioavailability and plasma steadystate concentrations and clearance. Clozapine is metabolized by the cytochrome P450 oxidase enzyme family (CYP450). Cytochrome P450 1A2 (CYP1A2), which is polymorphically expressed in humans, is the main enzyme of clozapine metabolism. This case report addresses the influence of CYP1A2∗1F genetic polymorphism on cloza - pine metabolism, explains the primary non-response of a young patient with schizophrenia due to increased gene expression in homozygous genotype ∗1F/∗1F (increased metabolism of clozapine) and underlies the importance of personalizing schizophrenia treatment by means of genetic and other molecular tools, at least in the cases of "treatment resistance". © by Nadja P. Marić 2015.

The introduction of antipsychotic medication in the 1950s forever changed the outlook on the treatment of schizophrenia, although there is still a large proportion of patients who do not reach functional recovery. At least 30% of patients do not respond to clozapine, the tricyclic dibenzodiazepine with complex pharmacological actions, which was proven to be more effective than any other antipsychotic in the treatment of schizophrenia. According to most of the therapeutic guidelines for schizophrenia, clozapine is the third line therapy for patients who did not respond to other antipsychotics. Large inter-individual variability exists for clozapine bioavailability and plasma steadystate concentrations and clearance. Clozapine is metabolized by the cytochrome P450 oxidase enzyme family (CYP450). Cytochrome P450 1A2 (CYP1A2), which is polymorphically expressed in humans, is the main enzyme of clozapine metabolism. This case report addresses the influence of CYP1A2∗1F genetic polymorphism on cloza - pine metabolism, explains the primary non-response of a young patient with schizophrenia due to increased gene expression in homozygous genotype ∗1F/∗1F (increased metabolism of clozapine) and underlies the importance of personalizing schizophrenia treatment by means of genetic and other molecular tools, at least in the cases of "treatment resistance". © by Nadja P. Marić 2015.