Therapeutic carbamazepine (CBZ) and valproic acid (VPA) monitoring in children using saliva as a biologic fluid / Monitoramento terapêutico de carbamazepina e ácido valproico em saliva de crianças

OBJECTIVE: The aim of the study was to analyze retrospectively carbamazepine (CBZ) and valproic acid (VPA) salivary data collected from epileptic children during a 3-year period. METHODS: Saliva samples stimulated by citric acid were assayed by FPIA method. One hundred and three patients (aged 1-14 years) were in CBZ or VPA monotherapy or in CBZ-VPA combined therapy. RESULTS: VPA salivary levels were linearly related with daily dose, but a non-linear relationship was found for CBZ, in patients under monotherapy. VPA did not alter saliva CBZ concentration. Conversely, CBZ reduced VPA salivary levels. Non-responsive children displayed higher VPA concentrations. CBZ levels in uncontrolled patients showed non-significant difference in relation with controlled subjects even though their daily doses were higher. CONCLUSION: Citric acid stimulated saliva is reliable enough to perform therapeutic drug monitoring. Saliva drug levels in non-responsive patients would be explained according to the generalized efflux transporter overexpression hypothesis.

OBJETIVO: O objetivo deste estudo foi avaliar retrospectivamente por 3 anos a partir de dados salivares, as terapias com carbamacepina (CBZ) e ácido valproico (VPA) em pacientes pediátricos. MÉTODOS: Foram avaliadas amostras de saliva estimuladas com ácido cítrico por método FPIA em 103 pacientes (idades 1-14 anos) em monoterapia com CBZ ou VPA ou terapia combinada CBZ-VPA. RESULTADOS: Níveis salivares de VPA se relacionaram linearmente com a dose diária, e a relação não linear foi encontrada em pacientes com CBZ. VPA não alterou as concentrações salivares de CBZ, porém a CBZ reduziu os níveis salivares de VPA em pacientes com terapia combinada. Pacientes refratários apresentaram altas concentrações de VPA. Os níveis de CBZ em pacientes não controlados não apresentaram diferenças significativas em relação aos pacientes controlados quando as doses diárias foram mais elevadas. CONCLUSÃO: Saliva estimulada com ácido cítrico é adequada para o monitoramento terapêutico. Níveis da droga na saliva em pacientes que não responderam ao tratamento pode ser explicado pelo transporte de efluxo generalizado.

Assessing ADHD across settings: contributions of behavioral assessment to categorical decision making.

Adapted methods of behavioral assessment to assess home and school functioning in a way that maps directly to the Diagnostic and Statistical Manual of Mental Disorders (4th ed., [DSM-IV]; American Psychiatric Association, 1994). The study was conducted in a school-based sample with 5- to 12-year-old children referred to a school intervention team. A multigate set of procedures was used to assign children to one of 3 groups: attention deficit hyperactivity disorder (ADHD), inattentive group; ADHD, combined group; and a non-ADHD control group. The ADHD Rating Scale-IV was used to assess parent and teacher ratings of ADHD symptoms as delineated in DSM-IV. The findings suggest that the use of a fixed cutoff point (i.e., 6 or more symptoms), which is employed in the DSM-IV, is often not the best strategy for making diagnostic decisions. The optimal approach depends on whether diagnostic information is being provided by the parent or teacher and whether the purpose of assessment is to conduct a screening or a diagnostic evaluation. Also, the results indicate that a strategy that aggregates symptoms in the order in which they are accurate in predicting a diagnosis of ADHD is a more effective strategy than the approach used in DSM-IV, which aggregates any combination of a specific number of items. Implications for using methods of behavioral assessment to make diagnostic decisions using DSM-IV criteria are discussed.

Assessing ADHD and comorbid disorders in children: the Child Behavior Checklist and the Devereux Scales of Mental Disorders.

Evaluated discriminant validity and clinical utility of selected subscales of the Devereux Scales of Mental Disorders (DSMD; Naglieri, LeBuffe, & Pfeiffer, 1994) and the Child Behavior Checklist (CBCL; Achenbach, 1991a) in 228 children referred to a clinic for the evaluation and treatment of attention deficit hyperactivity disorder (ADHD). The DSMD is a multiaxial behavior rating scale that measures symptomatology for a broad range of child psychopathology as described in the Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev. [DSM-R-III] and 4th ed. [DSM-IV]; American Psychiatric Association, 1987, 1994). Discriminant function analyses as well as sensitivity, specificity, and predictive power analyses were computed to evaluate the discriminant validity and clinical utility of selected DSMD and CBCL subscales for assessing ADHD, oppositional defiant disorder (ODD), and anxiety disorders. Results indicated that the DSMD compared very favorably with the CBCL in the ability to discriminate between children with ADHD and those without ADHD and between children with comorbid ODD and anxiety disorders and children who did not meet criteria for these disorders. The DSMD Attention subscale may be somewhat better at ruling in ADHD combined subtype (ADHD-C) and ADHD inattentive subtype (ADHD-I) than the CBCL Attention Problems subscale, but the CBCL Attention Problems subscale may have slightly better utility than the DSMD Attention subscale in ruling out these subtypes. Both the CBCL and DSMD were more useful for ruling out than for ruling in ODD and anxiety disorders.

Patterns of comorbidity associated with subtypes of attention-deficit/hyperactivity disorder among 6- to 12-year-old children.

OBJECTIVE: To study externalizing and internalizing comorbidity patterns in 6- to 12-year-old children with attention-deficit/hyperactivity disorder (ADHD) combined subtype (n = 27), ADHD inattentive subtype (n = 26), and a normal control group (n = 33). METHOD: Children were assigned to groups on the basis of results of a parent structured interview, which reflected DSM-IV diagnostic criteria, and teacher ratings of ADHD symptoms. Comorbid problems were assessed via parent and child structured interviews and parent and teacher behavior ratings. RESULTS: Logistic regression analyses and multivariate analyses of covariance revealed that (1) children in the ADHD combined group were significantly more likely to have a diagnosis of oppositional defiant disorder and conduct disorder and had significantly higher scores on parent and teacher ratings of externalizing problems than children in the ADHD inattentive and control groups, (2) children in the ADHD combined and ADHD inattentive groups had significantly higher scores on parent and teacher ratings of internalizing problems than children in the control group, and (3) children in the clinical groups did not differ with regard to internalizing disorders. CONCLUSIONS: The results from this study indicate that a significant comorbidity exists between ADHD combined and oppositional defiant disorder/conduct disorder. Contrary to previous studies that were conducted using DSM-III diagnostic criteria for ADHD, no differences were found between ADHD combined and ADHD inattentive subtypes regarding internalizing disorders.