Mood disorders in children and adolescents: psychopharmacological treatment.

Mood disorders are the leading causes of morbidity and mortality in children and adolescence. As a result, many adolescents are treated with psychopharmacologic agents such as antidepressants and mood stabilizers. To date, research into the safety and efficacy of these medications has lagged behind clinical practice. Several controlled trials of antidepressants in this population have recently been completed or are ongoing, yet few controlled trials of mood stabilizers have been conducted. Although acute efficacy of antidepressants is being addressed, many questions remain about pharmacological treatment of early-onset mood disorders. This article will focus on unmet research needs for the psychopharmacologic treatment of child and adolescent mood disorders.

A SPECT HMPAO study of regional cerebral blood flow in depressed adolescents and normal controls.

1. The objective of this study was to compare the relative regional cerebral blood flow (rCBF) patterns of a group of adolescents with major depressive disorder (MDD) to a group of normal controls. 2. Seven adolescent patients with symptomatic MDD and 7 age- and gender-matched normal controls, underwent SPECT imaging with 99mTc-HMPAO while unmedicated and in a resting state. These subject's data were normalized to whole brain counts, oriented in Talairach space, and analyzed using a voxel-based, t-image approach. 3. The authors found relative rCBF increases in the depressed group as compared to normals in the right mesial temporal cortex, the right superior-anterior temporal lobe, and the left infero-lateral temporal lobe. We found rCBF decreases in the depressed group as compared to normals in the left parietal lobe, the anterior thalamus and the right caudate. 4. Adolescents with MDD show rCBF abnormalities similar to those found in adult MDD rCBF studies. Further controlled studies with larger numbers of MDD subjects and normal age- and gender-matched controls are necessary before any definitive conclusions can be made from these findings.

Sleep polysomnography as a predictor of recurrence in children and adolescents with major depressive disorder.

Adults with major depressive disorder (MDD) demonstrate certain sleep polysomnographic abnormalities, including sleep continuity disturbances, reduced slow-wave sleep, shortened rapid eye movement (REM) latency, and increased REM density. Findings of sleep EEG studies in depressed children and adolescents have yielded conflicting results, possibly because of methodological variations across the studies. Generally, however, studies have demonstrated that depressed children and adolescents exhibit less sleep continuity and non-REM sleep differences in comparison with control subjects than do adults. Thus, results from adult sleep polysomnography studies cannot necessarily be generalized to children and adolescents. Depressed adults who have reduced REM latency during the symptomatic episode appear more likely to have a relapse once treatment is discontinued than those with normal REM latency. No studies of the relationship between sleep polysomnographic variables and clinical course have been reported in depressed children and adolescents. Data for baseline clinical variables and 3 nights of sleep polysomnography were examined in 113 depressed children (< or = 12 yr; n = 51) and adolescents (> or = 13 yr; n = 62) (56 in-patients and 57 outpatients) where data was available on at least 1 yr of naturalistic follow-up. Subjects came from 2 studies of sleep polysomnography in children and adolescents with MDD. Clinical course was assessed using the Kiddie-Longitudinal Interval Follow-Up Evaluation (K-LIFE). This interview was used to define recovery from the index episode of MDD and recurrence, a new episode of meeting full criteria for MDD. Clinically, within 1 yr of initial evaluation 102/113 subjects had recovered from their index episode of depression (minimal or no symptoms for 60 d). Of the 102 subjects who recovered, 36 (35.3%) had a recurrence of MDD. The majority of subjects (55%) who had a recurrence were not on medication at the time of recurrence. Subjects who had a recurrence were more likely to report suicidal thoughts or attempts at baseline compared to those without a recurrence (67 vs. 37%; F = 8.77; p = 0.004). On baseline sleep polysomnography, subjects with a later recurrence had decreased sleep efficiency and delayed sleep onset (sleep latency > 10 min). Probability of recurrence at 12 months was 0.39 compared to 0.15 in subjects with non-delayed sleep onset (p = 0.005). Baseline suicidal ideation and sleep dysregulation on sleep polysomnography predicted recurrence in a large sample of depressed children and adolescents. Depression in children and adolescents is frequently a chronic, recurrent illness. Factors that can predict clinical course are important in increasing our understanding of depression in this age group.

Fluoxetine in child and adolescent depression: acute and maintenance treatment.

The objective was to present naturalistic 1-year follow-up information of 96 child and adolescent outpatients with major depressive disorder who had been randomized in an 8-week double-blind, placebo-controlled trial of fluoxetine. Subjects were children and adolescents, ages 8-18 years, who were entered in a randomized clinical trial of fluoxetine. Following the acute treatment trial, treatment was not controlled. At 6 months and 1 year, the subjects and parents were interviewed using the Kiddie Longitudinal Interval Follow-up Evaluation (K-LIFE) for course of depression. Eighty-seven of the 96 subjects were followed for 1 year. Of these, 74 (85%) recovered from the depressive episode during that time (47 on fluoxetine, 22 on no medication, and 5 on other antidepressants or lithium). Twenty-nine of the subjects (39%) who recovered had a recurrence of depression during the 1-year follow-up, with 55% of these occurring within 6 months. Results of this study are similar to adult studies, with respect to response and recovery of depressive episodes. Most patients (85%) recover from the episode within 1 year, but approximately 40% have a recurrence within 12 months, which is a higher recurrence rate than in adults. Recovery was associated with younger age, lower severity of depressive symptoms, higher family functioning, and fewer comorbid diagnoses. Recurrence, which occurs both on and off medication, was difficult to predict, as there was little clinical data associated with recurrence in this population.