[Show abstract][Hide abstract] ABSTRACT: Insomnia is evident in the majority of youth with depression, and is associated with poorer outcomes. There are limited data on the impact of insomnia in response to acute treatment, which is particularly relevant with serotonin-selective reuptake inhibitors, given their tendency to worsen sleep architecture.
Three hundred nine children and adolescents (ages 7-18 years) were randomized to fluoxetine (n=157) or placebo (n=152) for 8-9 weeks (Emslie et al.1997, 2002). Substantial insomnia at baseline was defined as a child's depression rating scale-revised [CDRS-R] sleep item ≥ 4. Outcome measures were CDRS-R, response, and remission.
Insomnia was reported in 172/309 (55.7%) youth, and was associated with higher depression severity and greater fatigue, suicidal ideation, physical complaints, and decreased concentration. While response rates were similar in those with or without insomnia overall (51.7% vs. 55.7%), there is a significant difference by age group. Among adolescents, those with insomnia were less likely to respond to fluoxetine (39.2%; 20/51) than those without (65.9%; 27/41; p=0.013), while in children on fluoxetine, those with insomnia were more likely to respond to fluoxetine (69.4%; 25/36) than those without insomnia (41.4%; 12/29; p=0.027). Insomnia did not impact the response to placebo in either age group. Within adolescents, the overall least squares means for CDRS-R total score (across the 8 weeks of treatment) were significantly different between those who had insomnia versus those who did not within the fluoxetine group (43.65 [SE=1.31] vs. 36.58[SE=1.45], F=12.69, df=1, 169, p=0.0005; d=0.82), but not within the placebo group (44.91[SE=1.34] vs. 43.75[SE=1.68], F=0.29, df=1, 179, p=0.591; d=0.15).
While adolescents reporting substantial insomnia were less likely to respond to antidepressant treatment than those without insomnia, children were more responsive to fluoxetine when they had insomnia. Additional intervention targeting sleep disturbance may be warranted in adolescents.
Journal of child and adolescent psychopharmacology 02/2012; 22(1):21-8. DOI:10.1089/cap.2011.0096 · 2.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Major depression in adolescents is a significant public health concern because of its frequency and severity. To examine the neurobiological basis of depression in this population, the authors studied functional activation characteristics of the brain before and after antidepressant treatment in antidepressant-naive depressed adolescents and healthy comparison subjects.
Depressed (N=19) and healthy (N=21) adolescents, ages 11 to 18 years, underwent functional MRI assessment while viewing fearful and neutral facial expressions at baseline and again 8 weeks later. The depressed adolescents received 8 weeks of open-label fluoxetine treatment after their baseline scan.
Voxel-wise whole brain analyses showed that depressed youths have exaggerated brain activation compared with healthy comparison subjects in multiple regions, including the frontal, temporal, and limbic cortices. The 8 weeks of fluoxetine treatment normalized most of these regions of hyperactivity in the depressed group. Region-of-interest analyses of the areas involved in emotion processing indicated that before treatment, depressed youths had significantly greater activations to fearful relative to neutral facial expressions than did healthy comparison subjects in the amygdala, orbitofrontal cortex, and subgenual anterior cingulate cortex bilaterally. Fluoxetine treatment decreased activations in all three regions, as compared with the repeat scans of healthy comparison subjects.
While effective treatments are available, the impact of depression and its treatment on the brain in adolescents is understudied. This study confirms increases in brain activation in untreated depressed adolescents and demonstrates reductions in these aberrant activations with treatment.
American Journal of Psychiatry 01/2012; 169(4):381-8. DOI:10.1176/appi.ajp.2011.11040615 · 12.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Knowing the timing of specific depressive symptom improvement will enable clinicians to prepare their patients well and improve treatment outcome, whereas recognizing which depressive symptoms may show delayed improvement will help clinicians to provide additional interventions early in treatment. In a prospective open-label fluoxetine study, we investigated the timing of depressive symptom improvement during acute treatment, and identified common remaining symptoms following 4, 8, and 12 weeks of acute treatment in depressed youths.
A total of 168 children and adolescents, aged 7-18 years, with primary diagnoses of major depressive disorder (MDD) received 12 weeks of fluoxetine treatment. Youths were evaluated using the Kiddie Schedule for Affective Disorders and Schizophrenia. The outcome measure included the Children's Depression Rating Scale-Revised.
All depressive symptoms improved, particularly during the first 4 weeks of acute treatment. Forty-seven percent of remitters reported at least one residual symptom following 12 weeks, with most common residual symptoms being impaired school performance, insomnia, and irritability.
Residual symptoms are common, even among remitters, at the end of 12 weeks of acute treatment. There is a need for clinicians to monitor symptom improvement and potentially provide additional interventions for the more resistant symptoms, such as insomnia and school performance.
Journal of child and adolescent psychopharmacology 10/2010; 20(5):423-30. DOI:10.1089/cap.2009.0116 · 2.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: : Less than half of youths achieve remission (minimal to no symptoms) after acute antidepressant treatment. Early identification of who will or will not respond to treatment and achieve remission may help clinicians formulate treatment decisions and shorten the time spent on ineffective treatments. In a prospective open-label fluoxetine study, we investigate indicators of acute treatment response and remission.
: One hundred sixty-eight children and adolescents, ages 7 to 18 years, with primary diagnoses of major depressive disorder received 12 weeks of fluoxetine treatment. The youths were evaluated using the Kiddie Schedule for Affective Disorders and Schizophrenia. The outcome measure included the Children's Depression Rating Scale-Revised.
: Positive first-degree family history of depression was the only baseline demographic and clinical characteristic that predicted a favorable treatment response (p =.01). The rate of symptom improvement, however, is a good indicator of acute treatment response. A significant symptom reduction (approximately 50%) by week 4 is needed to achieve remission at the end of acute treatment.
: This study demonstrated that the rate of symptom improvement during early weeks of acute fluoxetine treatment is a good indicator of remission. Treatment approach may be reevaluated and modified as early as week 4 during acute treatment.Clinical trials registration information-Determining Optimal Continuation Treatment Duration for Depressed Children and Adolescents. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00332787.
Journal of the American Academy of Child and Adolescent Psychiatry 01/2009; 48(1):71-8. DOI:10.1097/CHI.0b013e318190043e · 7.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We present results of a feasibility test of a sequential treatment strategy using continuation phase cognitive-behavioral therapy (CBT) to prevent relapse in youths with major depressive disorder (MDD) who have responded to acute phase pharmacotherapy.
Forty-six youths (ages 11-18 years) who had responded to 12 weeks of treatment with fluoxetine were randomized to receive either 6 months of continued antidepressant medication management (MM) or antidepressant MM plus relapse prevention CBT (MM+CBT). Primary outcome was time to relapse, defined as a Childhood Depression Rating Scale-Revised score of 40 or higher and 2 weeks of symptom worsening or clinical deterioration warranting alteration of treatment to prevent full relapse.
Cox proportional hazards regression, adjusting for depression severity at randomization and for the hazard of relapsing by age across the trial, revealed that participants in the MM treatment group had a significantly greater risk for relapse than those in the MM+CBT treatment group (hazard ratio = 8.80; 95% confidence interval 1.01-76.89; chi = 3.86, p =.049) during 6 months of continuation treatment. In addition, patient satisfaction was significantly higher in the MM+CBT group. No differences were found between the two treatment groups on attrition rate, serious adverse events, and overall global functioning.
These preliminary results suggest that continuation phase CBT reduces the risk for relapse by eightfold compared with pharmacotherapy responders who received antidepressant medication alone during the 6-month continuation phase.
Journal of the American Academy of Child and Adolescent Psychiatry 11/2008; 47(12):1395-404. DOI:10.1097/CHI.0b013e31818914a1 · 7.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In the present study, we assess maternal depressive symptoms at the beginning and end of treatment to investigate the possible reciprocal relationship of maternal illness with the child's depressive illness and treatment.
We present data on 146 children and their mothers who were participating in a pediatric acute treatment study of fluoxetine. Patients were assessed with the Children's Depression Rating Scale-Revised at baseline and at each treatment visit. Mothers completed the Quick Inventory of Depressive Symptomatology-Self Report at baseline and end of acute treatment.
Thirty percent of mothers had moderate to severe levels of depressive symptoms at the child's baseline assessment. Overall, mothers reported improvement in maternal depressive symptoms at the end of their child's acute treatment, although maternal depression was not specifically targeted for intervention. Furthermore, mother's depressive symptoms appear to be associated with the child's depression severity both at the beginning and end of treatment. Mothers with higher levels of depressive symptoms had children with higher levels of depression severity at baseline and over the course of treatment. However, maternal depressive symptoms at baseline had no association with the rate of improvement of child depression severity.
This study indicates a positive relationship between the depression severity of mothers and their children. These findings highlight potential areas of intervention in the acute treatment of childhood depression.
Journal of the American Academy of Child and Adolescent Psychiatry 07/2008; 47(6):694-9. DOI:10.1097/CHI.0b013e31816bfff5 · 7.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The authors compared fluoxetine and placebo in continuation treatment to prevent relapse of major depressive disorder in children and adolescents.
After a detailed evaluation, children and adolescents 7-18 years of age with major depressive disorder were treated openly with fluoxetine. Those who had an adequate response after 12 weeks, as indicated by a Clinical Global Impression improvement score of 1 or 2 and a decrease of at least 50% in Children's Depression Rating Scale-Revised score, were randomly assigned to receive fluoxetine or placebo for an additional 6 months. The primary outcome measures were relapse and time to relapse. Relapse was defined as either a score of 40 or higher on the Children's Depression Rating Scale with a history of 2 weeks of clinical deterioration, or clinical deterioration as judged by the clinician. Additional analyses were conducted with relapse defined only as a score of 40 or higher on the Children's Depression Rating Scale.
Of 168 participants enrolled in acute fluoxetine treatment, 102 were randomly assigned to continuation treatment with fluoxetine (N=50) or placebo (N=52). Of these, 21 participants (42.0%) in the fluoxetine group relapsed, compared with 36 (69.2%) in the placebo group, a significant difference. Similarly, under the stricter definition of relapse, fewer participants in the fluoxetine group relapsed (N=11; 22.0%) than in the placebo group (N=25; 48.1%). Time to relapse was significantly shorter in the placebo group.
Continuation treatment with fluoxetine was superior to placebo in preventing relapse and in increasing time to relapse in children and adolescents with major depression.
American Journal of Psychiatry 05/2008; 165(4):459-67. DOI:10.1176/appi.ajp.2007.07091453 · 12.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recent acute efficacy trials of antidepressants in youth have suggested that high placebo-response rates in children (< 12 years of age) indicate that children may be more responsive to non-specific treatment interventions. Yet, these studies generally have not presented age-specific outcome data. The objective of this study was to compare the efficacy outcomes for children (< 12 years of age) and adolescents (> or = 12 years of age) using the combined data from two previously published double-blind, placebo-controlled trials of fluoxetine.
Children (< 12 years of age) and adolescents (> or = 12 years of age) with major depressive disorder were randomized to fluoxetine or placebo for 8-9 weeks of treatment. Outcome was assessed using the Children's Depression Rating Scale-Revised (CDRS-R) and Clinical Global Impressions scale.
Random regression of the CDRS-R showed a treatment group by age group interaction (F(1,338)=4.10, P=.044), indicating that the treatment effect was significantly more pronounced in children than adolescents. Within children, response at exit to fluoxetine was significantly better than placebo (56.9% vs 33.3%; P=.009). Adolescent response rates at exit were not significantly different between the groups (51.1% vs 38.6%; P=.128). Remission rates were low for both groups.
In the combined fluoxetine trials, drug-placebo difference was greater in children compared with adolescents. Contrary to expectations, the placebo-response rate was lower in the children than the adolescents.