Michael Sweeney

Efficacy of Paroxetine in the Treatment of Adolescent Major Depression: A Randomized, Controlled Trial

OBJECTIVE To compare paroxetine with placebo and imipramine with placebo for the treatment of adolescent depression. METHOD After a 7- to 14-day screening period, 275 adolescents with major depression began 8 weeks of double-blind paroxetine (20-40 mg), imipramine (gradual upward titration to 200-300 mg), or placebo. The two primary outcome measures were endpoint response (Hamilton Rating Scale for Depression [HAM-D] score < or = 8 or > or = 50% reduction in baseline HAM-D) and change from baseline HAM-D score. Other depression-related variables were (1) HAM-D depressed mood item; (2) depression item of the Schedule for Affective Disorders and Schizophrenia for Adolescents-Lifetime version (K-SADS-L); (3) Clinical Global Impression (CGI) improvement scores of 1 or 2; (4) nine-item depression subscale of K-SADS-L; and (5) mean CGI improvement scores. RESULTS Paroxetine demonstrated significantly greater improvement compared with placebo in HAM-D total score < or = 8, HAM-D depressed mood item, K-SADS-L depressed mood item, and CGI score of 1 or 2. The response to imipramine was not significantly different from placebo for any measure. Neither paroxetine nor imipramine differed significantly from placebo on parent- or self-rating measures. Withdrawal rates for adverse effects were 9.7% and 6.9% for paroxetine and placebo, respectively. Of 31.5% of subjects stopping imipramine therapy because of adverse effects, nearly one third did so because of adverse cardiovascular effects. CONCLUSIONS Paroxetine is generally well tolerated and effective for major depression in adolescents.

Fluvoxamine for the Treatment of Anxiety Disorders in Children and Adolescents

BACKGROUND Drugs that selectively inhibit serotonin reuptake are effective treatments for adults with mood and anxiety disorders, but limited data are available on the safety and efficacy of serotonin-reuptake inhibitors in children with anxiety disorders. METHODS We studied 128 children who were 6 to 17 years of age; who met the criteria for social phobia, separation anxiety disorder, or generalized anxiety disorder; and who had received psychological treatment for three weeks without improvement. The children were randomly assigned to receive fluvoxamine (at a maximum of 300 mg per day) or placebo for eight weeks and were evaluated with rating scales designed to assess the degree of anxiety and impairment. RESULTS Children in the fluvoxamine group had a mean (+/-SD) decrease of 9.7+/-6.9 points in symptoms of anxiety on the Pediatric Anxiety Rating Scale (range of possible scores, 0 to 25, with higher scores indicating greater anxiety), as compared with a decrease of 3.1+/-4.8 points among children in the placebo group (P<0.001). On the Clinical Global Impressions-Improvement scale, 48 of 63 children in the fluvoxamine group (76 percent) responded to the treatment, as indicated by a score of less than 4, as compared with 19 of 65 children in the placebo group (29 percent, P<0.001). Five children in the fluvoxamine group (8 percent) discontinued treatment because of adverse events, as compared with one child in the placebo group (2 percent). CONCLUSIONS Fluvoxamine is an effective treatment for children and adolescents with social phobia, separation anxiety disorder, or generalized anxiety disorder.

The Pediatric Anxiety Rating Scale (PARS): Development and psychometric properties

OBJECTIVE To describe the development and psychometric properties of the Pediatric Anxiety Rating Scale (PARS), a clinician-rated instrument for assessing the severity of anxiety symptoms associated with common DSM-IV anxiety disorders (social phobia, separation anxiety disorder, and generalized anxiety disorder) in children. METHOD As part of a multisite study of the efficacy of fluvoxamine, 128 children (aged 6-17) and their parents were interviewed weekly with the PARS. Data from multiple raters on a subsample of children (using live and videotaped interviews) were used to evaluate interrater reliability. Internal consistency, test-retest reliability, and validity (convergent, divergent) also were evaluated. RESULTS The PARS showed high interrater reliability, adequate test-retest reliability, and fair internal consistency. Convergent and divergent validity were satisfactory. PARS scores were sensitive to treatment and paralleled change in other measures of anxiety symptoms and global improvement. CONCLUSIONS The PARS is a useful clinician-rated instrument for assessing pediatric anxiety symptoms, severity, and impairment, particularly in treatment studies. Further study of the psychometric properties is warranted.

Attention Bias toward Threat in Pediatric Anxiety Disorders.

OBJECTIVE To examine attention bias toward threat faces in a large sample of anxiety-disordered youths using a well-established visual probe task. METHOD Study participants included 101 children and adolescents (ages 7-18 years) with generalized anxiety disorder, social phobia, and/or separation anxiety disorder enrolled in a multisite anxiety treatment study. Nonanxious youths (n = 51; ages 9-18 years) were recruited separately. Participants were administered a computerized visual probe task that presents pairs of faces portraying threat (angry), positive (happy), and neutral expressions. They pressed a response key to indicate the spatial location of a probe that replaced one of the faces on each trial. Attention bias scores were calculated from response times to probes for each emotional face type. RESULTS Compared to healthy youths, anxious participants demonstrated a greater attention bias toward threat faces. This threat bias in anxious patients did not significantly vary across the anxiety disorders. There was no group difference in attention bias toward happy faces. CONCLUSIONS These results suggest that pediatric anxiety disorders are associated with an attention bias toward threat. Future research may examine the manner in which cognitive bias in anxious youths changes with treatment.

Treatment for Adolescents with Depression Study (TADS): Rationale, design, and methods

OBJECTIVES A rapidly growing empirical literature on the treatment of major depressive disorder (MDD) in youth supports the efficacy of short-term treatment with depression-specific cognitive-behavioral therapy or medication management with a selective serotonin reuptake inhibitor. These studies also identify a substantial probability of partial response and of relapse, which might be addressed by more intensive, longer-term treatments. METHOD Funded by the National Institute of Mental Health, the Treatment for Adolescents With Depression Study (TADS) is a multicenter, randomized, masked effectiveness trial designed to evaluate the short-term (12-week) and long-term (36-week) effectiveness of four treatments for adolescents with MDD: fluoxetine, cognitive-behavioral therapy, their combination, and, acutely, pill placebo. A volunteer sample of 432 subjects aged 12-17 years (inclusive) with a primary DSM-IV diagnosis of MDD who are broadly representative of patients seen in clinical practice will enter the study. The primary dependent measures rated blindly by an independent evaluator are the Childrens Depression Rating Scale and, for responder analysis, a dichotomized Clinical Global Impressions-Improvement score. Consistent with an intent-to-treat analysis, all patients, regardless of treatment status, return for all scheduled assessments. RESULTS This report describes the design of the trial, the rationale for the design choices made, and the methods used to carry out the trial. CONCLUSION When completed, TADS will improve our understanding of how best to initiate treatment for adolescents with MDD.

The Treatment for Adolescents With Depression Study (TADS): outcomes over 1 year of naturalistic follow-up.

OBJECTIVE The Treatment for Adolescents With Depression Study (TADS) evaluates the effectiveness of fluoxetine, cognitive-behavioral therapy (CBT), and their combination in adolescents with major depressive disorder. The authors report effectiveness outcomes across a 1-year naturalistic follow-up period. METHOD The randomized, controlled trial was conducted in 13 academic and community sites in the United States. Stages I, II, and III consisted of 12, 6, and 18 weeks of acute, consolidation, and continuation treatment, respectively. Following discontinuation of TADS treatments at the end of stage III, stage IV consisted of 1 year of naturalistic follow-up. The participants were 327 subjects between the ages of 12 and 17 with a primary DSM-IV diagnosis of major depressive disorder. No TADS treatment was provided during the follow-up period; treatment was available in the community. The primary dependent measures, rated by an independent evaluator blind to treatment status, were the total score on the Childrens Depression Rating Scale-Revised and the rate of response, defined as a rating of much or very much improved on the Clinical Global Impressions improvement measure. RESULTS Sixty-six percent of the eligible subjects participated in at least one stage IV assessment. The benefits seen at the end of active treatment (week 36) persisted during follow-up on all measures of depression and suicidality. CONCLUSIONS In contrast to earlier reports on short-term treatments, in which worsening after treatment is the rule, the longer treatment in the TADS was associated with persistent benefits over 1 year of naturalistic follow-up.

Implementation challenges to TADS cognitive-behavioral therapy

This article discusses treatment obstacles that were frequently encountered by CBT therapists in the Treatment for Adolescents With Depression Study (TADS) trial. The most common or challenging treatment obstacles and their respective solutions were distilled from the minutes of national conference calls attended by TADS CBT supervisors and therapists. Obstacles were categorized into the following 6 themes: (1) comorbid disorders (i.e., anxiety, conduct, attention problems, and learning disorders); (2) severe depressive symptoms (i.e., anhedonia and hopelessness); (3) self-harm and suicidal ideation; (4) school refusal; (5) interpersonal factors, and; (6) treatment noncompliance. Case illustrations are provided throughout to illustrate these treatment obstacles and how they were addressed within the treatment manual.

African-American and Latino families in TADS: Recruitment and treatment considerations

The goal of this article is to review the experiences of some of the African-American and Lutino families who participated in the Treatment for Adolescents With Depression Study (TADS). The importance of this article derives from the historical and current inequities in mental health care for families of color. We describe the attempts within the TADS study to ensure an appropriate representation of families of color, a description of the age, and of the length and severity of depression of the African-American and Latino adolescents who participated in the TADS trial. The article additionally attempts, through case example, to convey the experiences of several of the African-American and Latino families who participated in TADS.