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Objective: To present the design, methods, and rationale of the Child/Adolescent Anxiety Multimodal Study (CAMS), a recently completed federally-funded, multi-site, randomized placebo-controlled trial that examined the relative efficacy of cognitive-behavior therapy (CBT), sertraline (SRT), and their combination (COMB) against pill placebo (PBO) for the treatment of separation anxiety disorder (SAD), generalized anxiety disorder (GAD) and social phobia (SoP) in children and adolescents., Methods: Following a brief review of the acute outcomes of the CAMS trial, as well as the psychosocial and pharmacologic treatment literature for pediatric anxiety disorders, the design and methods of the CAMS trial are described., Results: CAMS was a six-year, six-site, randomized controlled trial. Four hundred eighty-eight (N = 488) children and adolescents (ages 7-17 years) with DSM-IV-TR diagnoses of SAD, GAD, or SoP were randomly assigned to one of four treatment conditions: CBT, SRT, COMB, or PBO. Assessments of anxiety symptoms, safety, and functional outcomes, as well as putative mediators and moderators of treatment response were completed in a multi-measure, multi-informant fashion. Manual-based therapies, trained clinicians and independent evaluators were used to ensure treatment and assessment fidelity. A multi-layered administrative structure with representation from all sites facilitated cross-site coordination of the entire trial, study protocols and quality assurance., Conclusions: CAMS offers a model for clinical trials methods applicable to psychosocial and psychopharmacological comparative treatment trials by using state-of-the-art methods and rigorous cross-site quality controls. CAMS also provided a large-scale examination of the relative and combined efficacy and safety of the best evidenced-based psychosocial (CBT) and pharmacologic (SSRI) treatments to date for the most commonly occurring pediatric anxiety disorders. Primary and secondary results of CAMS will hold important implications for informing practice-relevant decisions regarding the initial treatment of youth with anxiety disorders., Trial Registration: ClinicalTrials.gov NCT00052078.

Recent controversies surrounding the use of selective serotonin reuptake inhibitors (SSRIs) have highlighted the need to reassess potential benefits, as well as potential risks of this class of medications in the treatment of pediatric depression. The recent availability of data from meta-analyses of published and unpublished antidepressant trials, epidemiological studies, and the Treatment for Adolescents with Depression Study (TADS) has facilitated a reanalysis of this risk/benefit relationship. Despite reviewing similar data, various regulatory agencies have arrived at rather disparate conclusions regarding the data, resulting in continued controversy. Although all groups appear to agree that careful assessment, education regarding risks, and closer monitoring are essential for SSRIs, only the U.S. Food and Drug Administration (FDA) and the U.K. Medicine and Health Care Products Regulatory Agency maintain that an acceptable risk/benefit relationship exists for fluoxetine. The European Medicines Agency concluded that the SSRIs should not be used in the treatment of depression in children and adolescents. The authors of this review have taken into consideration many of these same data and offer a critical discussion of the pros and cons of SSRIs in pediatric depression. The authors have concluded that SSRIs -- in particular, fluoxetine -- do have a role in the treatment of pediatric depression.

Background: Although psychotherapy has traditionally been the dominant form of treatment for children and adolescents with depression, there has been a recent increase in the prescription of antidepressants for this age group., Objective: To describe patterns of outpatient treatment for children and adolescents with depression., Design and Setting: Analysis of health service-use data from 4 consecutive years (1996-1999) of the Medical Expenditure Panel Survey, a nationally representative annual survey of the general population that is sponsored by the Agency for Healthcare Quality and Research, Rockville, Md. Subjects Patients aged 6 to 18 years who made 1 or more outpatient visits for the treatment of depression., Main Outcome Measures: Rate of treatment, mental health problems, psychotropic medication use, psychotherapy use, number of outpatient treatment visits, and type of provider., Results: Across the 4 survey years, the mean annual rate of outpatient treatment for depression was 0.93 per 100 individuals. The rate of treatment was especially low for African American individuals (0.23 per 100) and uninsured individuals (0.43 per 100). Approximately three quarters (79%) of treated children and adolescents received psychotherapy and more than half (56.9%) were prescribed antidepressant medications. The mean number of treatment visits for depression was 7.8 per year. As compared with children and adolescents with depression who were treated without antidepressants, those who received antidepressants were significantly more likely to have evidence of anhedonia, to live in large urban communities, to have parents who graduated from high school, and to have health insurance., Conclusions: The rate and pattern of treatment suggest that serious gaps exist in access to community outpatient treatment for children and adolescents with depression. At the same time, antidepressant medications are used far more commonly than would be expected on the basis of published treatment recommendations.

Background: Chronic depressions commonly present in youth and cause significant morbidity. No treatment studies in this age group are currently available., Methods: 19 pediatric subjects with dysthymic disorder or 'double depression' were recruited. After four weeks of psychosocial treatment, subjects failing to improve began open treatment with fluoxetine (20 mg) for eight weeks. Subjects were then reassessed for treatment response., Results: Fifteen subjects entered the medication phase, and eleven (73%) no longer met criteria for dysthymic disorder or Major Depression at final assessment., Conclusions: Fluoxetine shows promise as a safe and effective treatment for youth with chronic depressions. Controlled trials are indicated., Limitations: Open label design, no comparison treatment condition., Clinical Relevance: As in adults, treatment with antidepressants may prove to be a useful intervention with children and adolescents with chronic forms of depression.

Objective: To examine the impact of age on the effects of desipramine (DMI) on autonomic input to the heart., Method: Twenty-four-hour electrocardiograms were obtained from 42 subjects, aged 7 to 66 years, while off and on DMI. To obtain measures of autonomic input to the heart, heart rate variability was assessed via spectral analysis of RR interval variability., Results: DMI treatment was associated with a significant increase in 24-hour mean heart rate and significant decreases in RR interval variability in all spectral bands, including in the high-frequency band, which provides a measure of parasympathetic input to the heart. RR interval variability was greater in younger individuals both off and on DMI., Conclusions: DMI treatment was associated with a marked decline in RR interval variability, indicating that DMI affects autonomic input to the heart. Specifically, DMI reduced parasympathetic input, which, in theory, may increase vulnerability to arrhythmias. However, the magnitude of DMI's impact on RR interval variability did not vary with age.

Objective: In light of recent reports of sudden death in children being treated with desipramine (DMI), 3 of which were associated with physical exercise, the authors examined the effects of DMI on exercise in children and adults before and during DMI treatment., Method: Before treatment, 22 subjects (9 children, 13 adults) participated in a graded treadmill exercise test. Outcome measures included exercise tolerance, cardiovascular, and electrocardiographic parameters at progressive intensity levels and serum norepinephrine (NE) levels before and after exercise testing. Subjects were then treated with DMI, titrated to an average DMI dosage of 3 mg/kg, and underwent repeated exercise testing., Results: DMI treatment was associated with a significant elevation of circulating NE levels in the pre-exercise assessment. Exercise tolerance was not affected by DMI, and blood pressure and heart rate effects were modest. The cardiovascular impact of DMI treatment was similar in children and adults. One 31-year-old subject exhibited a brief episode of ventricular tachycardia associated with exercise during DMI treatment., Conclusions: DMI has only minor effects on the cardiovascular response to exercise, and these effects do not appear age-related. However, DMI may increase the risk of exercise-associated arrhythmias in rare individuals.