Browsing by Author "Todorovic, Dejan (58383597600)"

Because moclobemide pharmacokinetics vary considerably among individuals, monitoring of plasma concentrations lends insight into its pharmacokinetic behavior and enhances its rational use in clinical practice. The aim of this study was to evaluate whether single concentration-time points could adequately predict moclobemide systemic exposure. Pharmacokinetic data (full 7-point pharmacokinetic profiles), obtained from 21 depressive inpatients receiving moclobemide (150 mg 3 times daily), were randomly split into development (n = 18) and validation (n = 16) sets. Correlations between the single concentration-time points and the area under the concentration-time curve within a 6-hour dosing interval at steady-state (AUC0-6) were assessed by linear regression analyses. The predictive performance of single-point sampling strategies was evaluated in the validation set by mean prediction error, mean absolute error, and root mean square error. Plasma concentrations in the absorption phase yielded unsatisfactory predictions of moclobemide AUC 0-6. The best estimation of AUC0-6 was achieved from concentrations at 4 and 6 hours following dosing. As the most reliable surrogate for moclobemide systemic exposure, concentrations at 4 and 6 hours should be used instead of predose trough concentrations as an indicator of between-patient variability and a guide for dose adjustments in specific clinical situations. © 2011 The Author(s).

Because moclobemide pharmacokinetics vary considerably among individuals, monitoring of plasma concentrations lends insight into its pharmacokinetic behavior and enhances its rational use in clinical practice. The aim of this study was to evaluate whether single concentration-time points could adequately predict moclobemide systemic exposure. Pharmacokinetic data (full 7-point pharmacokinetic profiles), obtained from 21 depressive inpatients receiving moclobemide (150 mg 3 times daily), were randomly split into development (n = 18) and validation (n = 16) sets. Correlations between the single concentration-time points and the area under the concentration-time curve within a 6-hour dosing interval at steady-state (AUC0-6) were assessed by linear regression analyses. The predictive performance of single-point sampling strategies was evaluated in the validation set by mean prediction error, mean absolute error, and root mean square error. Plasma concentrations in the absorption phase yielded unsatisfactory predictions of moclobemide AUC 0-6. The best estimation of AUC0-6 was achieved from concentrations at 4 and 6 hours following dosing. As the most reliable surrogate for moclobemide systemic exposure, concentrations at 4 and 6 hours should be used instead of predose trough concentrations as an indicator of between-patient variability and a guide for dose adjustments in specific clinical situations. © 2011 The Author(s).

There is an ongoing debate on the relationship between depression and anxiety, but data on similarities and differences in their predictor profiles are scarce. The aim of our study was to compare family and personality predictors of these disorders among 220 "emerging adults." As such, two clinical groups with noncomorbid depressive and anxiety disorders, and one healthy control group were assessed by sociodemographic questionnaires, Structured Clinical Interview for DSM-IV Disorders and NEO Personality Inventory, Revised. We found significant overlap in family and personality risk profiles, with increasing effect size for predictors common to anxiety and depression when the categories "no disorder-Anxiety disorder-depressive disorder" were considered as existing along a continuum. Among the contributing factors we assessed, family psychiatric history, family structure and conflicts with parents were more significant than personality traits. Our study indicates that emerging adults may be more vulnerable to depression than anxiety in the presence of family and personality risk factors. © 2018 Wolters Kluwer Health, Inc. All rights reserved.

What is already known about this subject • Moclobemide (MCB) undergoes extensive both presystemic and systemic metabolism that can be affected by concomitant drugs. • Valproic acid (VPA) and carbamazepine (CBZ) have been found to interact with psychotropic medications of all classes and many other drugs; VPA acts as a broad-spectrum inhibitor, and CBZ as a potent inducer of a variety of drug-metabolizing enzymes. • There have been no previous studies designed to investigate a potential pharmacokinetic (PK) interaction between MCB and VPA or CBZ; however, these agents are likely to be used concomitantly for the treatment of depressive disorders. What this study adds • VPA does not significantly affect PK or metabolism of MCB at steady state. • CBZ significantly decreases MCB exposure. This effect is time-dependent, being more pronounced after 3-5 weeks of co-administration. Aim: To assess the impact of valproic acid (VPA) and carbamazepine (CBZ) on moclobemide (MCB) pharmacokinetics (PK) and metabolism at steady state in depressive patients. Methods: Twenty-one inpatients with recurrent endogenous depression received MCB (150 mg t.i.d.), either as monotherapy or in combination with VPA (500 mg b.i.d.) or CBZ (200 mg b.i.d.) in a nonrandomized manner. Steady-state plasma PK parameters of MCB and its two metabolites, Ro 12-8095 and Ro 12-5637, were derived. Clinical assessments of treatment efficacy were performed weekly using standard depression rating scales. Results: CBZ, but not VPA, was associated with decreases in the MCB AUC by 35% [from 7.794 to 5.038 mg h l-1; 95% confidence interval (CI) -4.84863, -0.66194; P = 0.01] and Cmax by 28% (from 1.911 to 1.383 mg l-1; 95% CI -0.98197, -0.07518; P < 0.05), and an increase in its oral clearance by 41% (from 0.323 to 0.454 l h-1 kg-1; 95% CI 0.00086, 0.26171; P < 0.05) after 4 weeks of co-administration. MCB through concentrations were also decreased, on average by 41% (from 0.950 to 0.559 mg l-1; 95% CI -0.77479, -0.03301; P < 0.05). However, the efficacy in this group of patients was not inferior to the controls, for several possible reasons. Overall tolerability of all study medications was good. Conclusions: VPA does not significantly affect PK or metabolism of MCB, whereas CBZ time-dependently decreases MCB exposure, probably by inducing metabolism of MCB and its major plasma metabolite. The actual clinical relevance of the observed MCB-CBZ PK interaction needs to be further evaluated in a more comprehensive study. © 2008 The British Pharmacological Society.

What is already known about this subject • Moclobemide (MCB) undergoes extensive both presystemic and systemic metabolism that can be affected by concomitant drugs. • Valproic acid (VPA) and carbamazepine (CBZ) have been found to interact with psychotropic medications of all classes and many other drugs; VPA acts as a broad-spectrum inhibitor, and CBZ as a potent inducer of a variety of drug-metabolizing enzymes. • There have been no previous studies designed to investigate a potential pharmacokinetic (PK) interaction between MCB and VPA or CBZ; however, these agents are likely to be used concomitantly for the treatment of depressive disorders. What this study adds • VPA does not significantly affect PK or metabolism of MCB at steady state. • CBZ significantly decreases MCB exposure. This effect is time-dependent, being more pronounced after 3-5 weeks of co-administration. Aim: To assess the impact of valproic acid (VPA) and carbamazepine (CBZ) on moclobemide (MCB) pharmacokinetics (PK) and metabolism at steady state in depressive patients. Methods: Twenty-one inpatients with recurrent endogenous depression received MCB (150 mg t.i.d.), either as monotherapy or in combination with VPA (500 mg b.i.d.) or CBZ (200 mg b.i.d.) in a nonrandomized manner. Steady-state plasma PK parameters of MCB and its two metabolites, Ro 12-8095 and Ro 12-5637, were derived. Clinical assessments of treatment efficacy were performed weekly using standard depression rating scales. Results: CBZ, but not VPA, was associated with decreases in the MCB AUC by 35% [from 7.794 to 5.038 mg h l-1; 95% confidence interval (CI) -4.84863, -0.66194; P = 0.01] and Cmax by 28% (from 1.911 to 1.383 mg l-1; 95% CI -0.98197, -0.07518; P < 0.05), and an increase in its oral clearance by 41% (from 0.323 to 0.454 l h-1 kg-1; 95% CI 0.00086, 0.26171; P < 0.05) after 4 weeks of co-administration. MCB through concentrations were also decreased, on average by 41% (from 0.950 to 0.559 mg l-1; 95% CI -0.77479, -0.03301; P < 0.05). However, the efficacy in this group of patients was not inferior to the controls, for several possible reasons. Overall tolerability of all study medications was good. Conclusions: VPA does not significantly affect PK or metabolism of MCB, whereas CBZ time-dependently decreases MCB exposure, probably by inducing metabolism of MCB and its major plasma metabolite. The actual clinical relevance of the observed MCB-CBZ PK interaction needs to be further evaluated in a more comprehensive study. © 2008 The British Pharmacological Society.

The dynamics of adolescence require adjustments in psychiatric treatment because of the challenges of this developmental stage in life. This column describes the Day Hospital for Adolescents (DHA) of the Institute of Mental Health in Belgrade, Serbia, which was established in December 2007. The DHA is a holistic program for the treatment of youths ages 15-25 with emotional disorders. The multicomponent therapeutic program includes individual treatment, several group therapeutic activities, and work with patients' families and the school system. An evaluation of data obtained for 102 patients indicated that DHA treatment was associated with significant reductions in depression symptom severity and improved functioning. The adolescents reported a high level of treatment satisfaction. The results suggest that a multicomponent day hospital is an effective treatment modality for adolescents with emotional disorders.