Treatment for Adolescents with Depression Study (TADS): safety results.

OBJECTIVE: To compare the rates of physical, psychiatric, and suicide-related events in adolescents with MDD treated with fluoxetine alone (FLX), cognitive-behavioral therapy (CBT), combination treatment (COMB), or placebo (PBO). METHOD: Safety assessments included adverse events (AEs) collected by spontaneous report, as well as systematic measures for specific physical and psychiatric symptoms. Suicidal ideation and suicidal behavior were systematically assessed by self- and clinician reports. Suicidal events were also reanalyzed by the Columbia Group and expert raters using the Columbia-Classification Algorithm for Suicidal Assessment used in the U.S. Food and Drug Administration reclassification effort. RESULTS: Depressed adolescents reported high rates of physical symptoms at baseline, which improved as depression improved. Sedation, insomnia, vomiting, and upper abdominal pain occurred in at least 2% of those treated with FLX and/or COMB and at twice the rate of placebo. The rate of psychiatric AEs was 11% in FLX, 5.6% in COMB, 4.5% in PBO, and 0.9% in CBT. Suicidal ideation improved overall, with greatest improvement in COMB. Twenty-four suicide-related events occurred during the 12-week period: 5 patients (4.7%) in COMB, 10 (9.2%) in FLX, 5 (4.5%) in CBT, and 3 (2.7%) in placebo. Statistically, only FLX had more suicide-related events than PBO (p =.0402, odds ratio (OR) = 3.7, 95% CI 1.00-63.7). Only five actual attempts occurred (2 COMB, 2 FLX, 1 CBT, 0 PBO). There were no suicide completions. CONCLUSIONS: Different methods for eliciting AEs produce different results. In general, as depression improves, physical complaints and suicidal ideation decrease in proportion to treatment benefit. In this study, psychiatric AEs and suicide-related events are more common in FLX-treated patients. COMB treatment may offer a more favorable safety profile than medication alone in adolescent depression

Effects of atomoxetine on growth in children with attention-deficit/hyperactivity disorder following up to five years of treatment.

OBJECTIVE: To examine the effects on growth of long-term pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD), we present findings from an ongoing 5-year study of the efficacy and safety of treatment with atomoxetine. METHODS: North American patients, 6-17 years old at study entry (N = 1,312) and with Diagnostic and Statistical Manual of Mental Disorders,4th edition (DSM-IV) ADHD, were studied under open-label atomoxetine treatment. Sixty-one were studied up to 5 years. RESULTS: After 1 month\u27s treatment, patients weighed less than expected from their starting percentiles relative to population norms, with a maximum shortfall at 15 months and a return to expected weight by 36 months. Patients were slightly shorter than expected after 12 months, reaching a maximum shortfall at 18 months and returning to expected height by 24 months. Patients in the top quartile for body mass index (BMI) or weight at baseline, and those in the third quartile for height, showed 5-year decreases from expected values. Those below median height at baseline showed increases relative to expected values. CONCLUSIONS: These interim results indicate that continuous atomoxetine treatment for up to 5 years has little or no long-term effect on juvenile growth and final stature for most patients, although persistent decreases from expected may occur in some patients who are larger than average before treatment

In Search of HPA Axis Dysregulation in Child and Adolescent Depression

Dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis in adults with major depressive disorder is among the most consistent and robust biological findings in psychiatry. Given the importance of the adolescent transition to the development and recurrence of depressive phenomena over the lifespan, it is important to have an integrative perspective on research investigating the various components of HPA axis functioning among depressed young people. The present narrative review synthesizes evidence from the following five categories of studies conducted with children and adolescents: (1) those examining the HPA system’s response to the dexamethasone suppression test (DST); (2) those assessing basal HPA axis functioning; (3) those administering corticotropin-releasing hormone (CRH) challenge; (4) those incorporating psychological probes of the HPA axis; and (5) those examining HPA axis functioning in children of depressed mothers. Evidence is generally consistent with models of developmental psychopathology that hypothesize that atypical HPA axis functioning precedes the emergence of clinical levels of depression and that the HPA axis becomes increasingly dysregulated from child to adult manifestations of depression. Multidisciplinary approaches and longitudinal research designs that extend across development are needed to more clearly and usefully elucidate the role of the HPA axis in depression

Using behavior rating scales for ADHD across ethnic groups: The IOWA Conners

Abstract: In this study we examined the normative and construct equivalence of the teacher IOWA Conners Rating Scale (IOWA) in a sample of 3,998 elementary school children (2,124 African American and 1,874 European American) ages 5 to 11 years in an urban school district. Risk odds ratios (% > 2 SD) were calculated by gender and ethnicity. An exploratory Principal Axis factor analysis was performed to determine the appropriateness of the 2-factor model. Structural equation modeling was used to estimate the degree of fit for the 2-factor model. Both African American boys and girls received significantly higher scores than their European American counterpoints.There was a 2.48 to 3.51 greater likelihood forAfrican American boys and a 3.60 to 5.27 greater likelihood of African American girls to be rated > 2 SD above the mean for inattention/overactivity, aggression, or IOWA Conners Rating Scale scores. A rater ethnicity by student ethnicity (European American vs. African American) interaction was also found. Confirmatory factor analysis indicated that the same 2-factor model was appropriat

Sub-national TIMES model for analyzing future regional use of biomass and biofuels in Sweden and France

International audienceThe objective of this study is to improve evaluations of the future use of biomass sources in Sweden and France by representing the high spatial variations of the supply and cost of biomass sources in energy system models. The proposed methodology considers a high spatial disaggregation of biomass supply sources, as well as detailed biomass cost-supply curves, and is thereby able to account for spatial differences in heterogeneous land qualities, management strategies, and possible adaptation rates. Integrating the methodology into national or regional energy system models will enhance cost-effective evaluations of biomass sources as well as the development of the bioenergy sector. A TIMES energy system model was used to evaluate bioenergy production potential for France and Sweden based on domestic biomass sources and under the assumption that bioenergy production should not be at the expense of domestic food and forestry supply. Results show that by 2050, the biomass sources considered could provide as much as 250PJ of bioenergy in Sweden, and 1470PJ of bioenergy in France. Results further showed that 1st generation biofuels are likely to continue to play a substantial role in the biofuel mix. While 2nd generation biofuel production in Sweden is likely to be low, larger amounts of 2nd generation biofuels could be produced in France. However, the amount and type of 2nd generation biofuel produced in France was found to be highly dependent on the bioenergy demand level