Effects of carvedilol on left ventricular function and oxidative stress in infants and children with idiopathic dilated cardiomyopathy: a 12-month, two-center, open-label study.

OBJECTIVES: This study was conducted to determine the effects of carvedilol adjunct to standard treatment on left ventricular function (LVF), estimated as ejection fraction (EF) and fractional shortening (FS) on echocardiography, in children with idiopathic dilated cardiomyopathy (DCM). A secondary end point was to characterize the antioxidant potential of carvedilol. METHODS: Hospitalized children aged 62.5 kg) was associated with significant decreases from baseline in systolic BP (130 [4] vs 123 [3] mm Hg; P<0.05), diastolic BP (85 [4] vs 77 [4] mm Hg; P<0.05), and HR (81 [4] vs 65 [4] bpm; P<0.001) after the first month of addition to standard therapy. At 6 months, there were significant improvements from baseline in EF (37.2% [2.4%] vs 50.2% [2.3%]; P<0.001) and FS (18.37% [2.00%] vs 23.58% [0.90%]; P<0.001). Modified NYHAC class was significantly improved in 80% of children (2.9 vs 2.3; P<0.001) at 12 months. The highest dose of carvedilol (0.8 mg/kg/d in children 62.5 kg) was well tolerated in all 21 children. No serious AEs that necessitated study drug discontinuation (tiredness, headache, vomiting) were observed. At baseline, mean (SE) erythrocyte SOD activity (2781 [116] vs 2406 [102] U/g Hb; P<0.05) and GR activity (5.3 [0.3] vs 3.0 [0.2] micromol nicotinamide adenine dinucleotide phosphate [NADPH]/min/g Hb; P<0.001) were significantly higher in children with DCM who received standard therapy compared with healthy controls.CAT activity (12.7[0.9] vs 18.5 [1.0]U/g Hb; P<0.001) was significantly lower, while GSH-Px was unchanged. At 6 and 12 months of therapy, carvedilol plus standard treatment was associated with significant decreases from baseline in SOD (2516 [126] and 2550 [118], respectively, vs 2781 [116] U/g Hb; both, P<0.001) and GR (4.7 [0.3] and 4.1 [0.2], respectively, vs 5.3 [0.2] micromol NADPH/min/g Hb; P<0.05 and P<0.001) and increased CAT (16.9 [1.0] and 16.4 [0.7], respectively, vs 12.7 [0.9] U/g Hb; both, P<0.001). CONCLUSIONS: These pediatric patients with DCM treated for 12 months with carvedilol (up to 0.8 mg/kg/d in children 62.5 kg) were found to have significant improvements in LVF and symptoms of HF. Twelve months of carvedilol therapy was associated with antioxidant enzyme activities near those observed in healthy children.

Antipsychotic polypharmacy at the University Psychiatric Hospital in Serbia.

The aim of the study was to analyse the prevalence of polypharmacy with antipsychotic drugs and analyse types of coprescribing episodes at the University Psychiatric Hospital in Serbia. A sample of 120 patients (198 hospitalisations) was analysed. The prevalence of polypharmacy was calculated as the proportion of patients receiving two or more antipsychotic drugs concomitantly for at least 28 days. Total daily antipsychotic drug load was calculated as the number of defined daily doses (DDDs) of drugs per patient per day. It was compared between patients receiving monotherapy and patients receiving polypharmacy. Statistics was performed using standard statistical methods. Monotherapy was prescribed during 32.3% hospitalisations (n = 64), while polypharmacy was noted in 67.7% (n = 134). Polypharmacy with two drugs was observed during 126 (63.6%) hospitalisations and three antipsychotics were prescribed concomitantly during 8 (4.1%) hospitalisations. Patients' characteristics were not significantly different between patients who received only monotherapy and patients receiving polypharmacy. Patients on monotherapy had significantly more prior hospitalisations than patients from the other group (t = 3.94, df = 119, p < 0.001). The prevalence of polypharmacy patient episodes (67.7%) is approximately 100% higher than the prevalence observed in developed European countries. The explanation of such prescribing habit of Serbian psychiatrists requires further investigation. The only distinguishing factor between patients receiving monotherapy and patients receiving polypharmacy is the number of prior hospitalisations.

Trends in consumption of psychiatric drugs in Serbia and Montenegro 2000-2004.

PURPOSE: To investigate the trends in psychiatric drugs utilization in Serbia and Montenegro over the 5-years period (2000-2004). MATERIALS AND METHODS: The wholesale data issued by the manufacturers or distributors were used. Also, the lists of drugs used from the Institute of Mental Health (institution which provides primary, secondary and tertiary psychiatric care) were used to corroborate the wholesale data. The utilization of drugs in general population was calculated using ATC/DDD methodology, and was expressed in Defined Daily Doses (DDD) per 1000 inhabitants per day. The utilization of drugs in the Institute of Mental Health was calculated from the hospital pharmacy records and was expressed as the number of DDDs per 100 bed-days. The statistics was performed using standard statistical methods. RESULTS: The general consumption of psychiatric drugs in Serbia and Montenegro significantly increased during the 2000-2004 period (from 45.1 DDD/1000 inhabitants/day in 2000 to 69.1 DDD/1000 inhour/day in 2004). The general utilization of anxiolytic/hypnotic drugs surged significantly, but the inhospital use remained rather stable. The most prominent changes were noted in the utilization of antidepressants, which doubled in that period, both in general and inhospital settings. Among antipsychotics in general population, there is a significant increase in the utilization of clozapine. In inhospital setting, there is a significant increase of total utilization of antipsychotic drugs, but this is also mainly on the account of atypicals. CONCLUSIONS: The total consumption of psychiatric drugs significantly increased. The utilization of anxiolytic/hypnotic drugs in 2004 reached 60 DDDs/1000 inhabitants/day, which is in collision with the trend in developed countries. It is necessary to form national guidelines for prescribing anxiolytic/hypnotic drugs, in order to rationalize their use. More favourable is the antidepressant (SSRIs in particular) and atypical antipsychotic drugs utilization increase.

Pattern of utilization of benzodiazepines in patients with hypertension: a pilot study.

BACKGROUND/AIM: The analysis of drug prescribing in general practice in Serbia showed that the use of benzodiazepines is most frequently associated with hypertension. The aim of this study was to establish the correlation of the characteristics of patients with hypertension to antihypertensive drug therapy, and the intake of benzodiazepines. METHODS: A special questionnaire was used for interviewing the patients (n = 171) chronically treated for hypertenson. Statistical tests used were chi2-test and Student's t-test. RESULTS: No differences were noted in terms of age, gender, education, body weight, smoking habits and blood pressure (155 +/- 4.9/100 +/- 2.7 mmHg vs. 160 +/- 2.2/105 +/- 3.7 mmHg), between the group I (antihypertensive drugs+benzodiazepines: n = 79), and the group II (antihypertensives only: n = 92). The patients taking benzodiazepines received a lower number of different antihypertensive drugs (2.3 +/- 0.09 vs. 2.7 +/- 0.10; p < 0.01), but the total antihypertensive drug load was significantly greater than in the group II (2.6 +/- 0.10 vs. 1.9 +/- 0.15 defined daily doses (DDD)/patient/day; p < 0.01). Benzodiazepines were taken for anxiety (62%) and hypertension (21%), rarely for insomnia, mostly once a day, at bedtime. About half the patients took benzodiazepines regularly for months or years aware of the risk for addiction. Diazepam was used by 82% of the patients. The average daily exposure to benzodiazepines was 0.45 +/- 0.05 DDD/patient/day. The drug was bought without prescription in 25% of the patients, and without consulting a physician in 12% of them. CONCLUSION: The study confirmed a close association of hypertension with the use of benzodiazepines. The frequent use of benzodiazepines in the patients with hypertension might be caused by an inadequate response to antihypertensive drug therapy, besides anxiety and insomnia. The therapeutic efficacy of a long-term use of low doses of benzodiazepines in hypertension requires further investigation.

Benzodiazepines utilization and self-medication as correlates of stress in the population of Serbia.

BACKGROUND: High consumption of benzodiazepines (BDZ) occurs in populations exposed to stress. In the last decade of the 20th century, when the population of Serbia experienced increasing economic hardships due to the civil war in former Yugoslavia, UN sanctions and air raids in 1999, diazepam became the most frequently prescribed drug. This period was also characterized by the free marketing of all drugs, which made them available without prescription. OBJECTIVE: To investigate the consumption and the pattern of use of BDZ in the population of Belgrade and Serbia in the period of 1990-2001. MATERIALS AND METHODS: Data on benzodiazepines prescribing and on wholesale in general population of Belgrade and Serbia were collected. In a cross-sectional study of drug prescribing in general practice data were obtained from 1800 patient records in the primary health care centers in Serbia. Statistical analysis was performed by using standard non-parametric tests. RESULTS: Annual rates of BDZ prescribing in Belgrade from 1990 to 1999 were rather uniform (approx. 25 DDD/1000 inhabitants/day), with slight tendency to decrease. In Serbia as a whole, there were significant differences in the annual prescribing rates over the period 1998-2000. The wholesale of BDZ in Serbia significantly increased between 1991 and 2001, with the peak of 133 DDD/1000 inhabitants/day in 1999. The wholesale of BDZ was significantly greater that the rates of prescribing in corresponding years. Over the 10 year period, the numbers of visits to GPs and psychiatrists and the number of neurotic diagnoses were significantly reduced. The use of BDZ in psychiatric hospital increased significantly in 1999 as compared to 1998, although the number of admissions and the occupancy of hospital beds were reduced. In primary health care, diazepam was the most frequently prescribed drug predominantly for non-psychiatric diagnoses. CONCLUSIONS: It is concluded that in the last decade, the utilization of BDZ was increased in the population of Belgrade and Serbia, indicating a clear trend to self-medication, particularly in the period of acute war crisis.