Selective serotonin reuptake inhibitors in pediatric depression: is the balance between benefits and risks favorable?

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 The recent availability of data from meta-analyses of published and unpublished antidepressant trials, epidemiological studies, and the Treatment for Adolescents with Depression Study (TADS) has facilitated a reanalysis of this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

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

A randomised controlled trial of the Neuro Emotional Technique (NET) for childhood Attention Deficit Hyperactivity Disorder (ADHD): a protocol

<p>Abstract</p> <p>Background</p> <p>An abundance of literature is dedicated to research for the treatment of Attention Deficit Hyperactivity Disorder (ADHD). Most, is in the area of pharmacological therapies with less emphasis in psychotherapy and psychosocial interventions and even less in the area of complementary and alternative medicine (CAM).</p> <p>The use of CAM has increased over the years, especially for developmental and behavioral disorders, such as ADHD. 60–65% of parents with children with ADHD have used CAM. Medical evidence supports a multidisciplinary approach (i.e. pharmacological and psychosocial) for the best clinical outcomes. The Neuro Emotional Technique (NET), a branch of Chiropractic, was designed to address the biopsychosocial aspects of acute and chronic conditions including non-musculoskeletal conditions. Anecdotally, it has been suggested that ADHD may be managed effectively by NET.</p> <p>Design/methods</p> <p>A placebo controlled, double blind randomised clinical trial was designed to assess the effectiveness of NET on a cohort of children with medically diagnosed ADHD.</p> <p>Children aged 5–12 years who met the inclusion criteria were randomised to one of three groups. The control group continued on their existing medical regimen and the intervention and placebo groups had the addition of the NET and sham NET protocols added to their regimen respectively. These two groups attended a clinical facility twice a week for the first month and then once a month for six months.</p> <p>The Conners' Parent and Teacher Rating Scales (CRS) were used at the start of the study to establish baseline data and then in one month and in seven months time, at the conclusion of the study. The primary outcome measures chosen were the Conners' ADHD Index and Conners' Global Index. The secondary outcome measures chosen were the DSM-IV: Inattentive, the DSM-IV:Hyperactive-Impulsive, and the DSM-IV:Total subscales from the Conners' Rating Scales, monitoring changes in inattention, hyperactivity and impulsivity.</p> <p>Calculations for the sample size were set with a significance level of 0.05 and the power of 80%, yielding a sample size of 93.</p> <p>Discussion</p> <p>The present study should provide information as to whether the addition of NET to an existing medical regimen can improve outcomes for children with ADHD.</p> <p>Trial registration</p> <p>Australian New Zealand Clinical Trial Registration Number: ANZCTRN 012606000332527</p

Child/Adolescent Anxiety Multimodal Study (CAMS): rationale, design, and methods

<p>Abstract</p> <p>Objective</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>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.</p> <p>Trial registration</p> <p>ClinicalTrials.gov NCT00052078.</p

Chiropractic care for paediatric and adolescent Attention-Deficit/Hyperactivity Disorder: A systematic review

<p>Abstract</p> <p>Background</p> <p>Psychostimulants are first line of therapy for paediatric and adolescent AD/HD. The evidence suggests that up to 30% of those prescribed stimulant medications do not show clinically significant outcomes. In addition, many children and adolescents experience side-effects from these medications. As a result, parents are seeking alternate interventions for their children. Complementary and alternative medicine therapies for behavioural disorders such as AD/HD are increasing with as many as 68% of parents having sought help from alternative practitioners, including chiropractors.</p> <p>Objective</p> <p>The review seeks to answer the question of whether chiropractic care can reduce symptoms of inattention, impulsivity and hyperactivity for paediatric and adolescent AD/HD.</p> <p>Methods</p> <p>Electronic databases (Cochrane CENTRAL register of Controlled Trials, Cochrane Database of Systematic reviews, MEDLINE, PsycINFO, CINAHL, Scopus, ISI Web of Science, Index to Chiropractic Literature) were searched from inception until July 2009 for English language studies for chiropractic care and AD/HD. Inclusion and exclusion criteria were applied to select studies. All randomised controlled trials were evaluated using the Jadad score and a checklist developed from the CONSORT (Consolidated Standards of Reporting Trials) guidelines.</p> <p>Results</p> <p>The search yielded 58 citations of which 22 were intervention studies. Of these, only three studies were identified for paediatric and adolescent AD/HD cohorts. The methodological quality was poor and none of the studies qualified using inclusion criteria.</p> <p>Conclusions</p> <p>To date there is insufficient evidence to evaluate the efficacy of chiropractic care for paediatric and adolescent AD/HD. The claim that chiropractic care improves paediatric and adolescent AD/HD, is only supported by low levels of scientific evidence. In the interest of paediatric and adolescent health, if chiropractic care for AD/HD is to continue, more rigorous scientific research needs to be undertaken to examine the efficacy and effectiveness of chiropractic treatment. Adequately-sized RCTs using clinically relevant outcomes and standardised measures to examine the effectiveness of chiropractic care verses no-treatment/placebo control or standard care (pharmacological and psychosocial care) are needed to determine whether chiropractic care is an effective alternative intervention for paediatric and adolescent AD/HD.</p

24- and 36-Week Outcomes for the Child/Adolescent Anxiety Multimodal Study (CAMS)

OBJECTIVE: We report active treatment group differences on response and remission rates and changes in anxiety severity at weeks 24 and 36 for the Child/Adolescent Anxiety Multimodal Study (CAMS). METHOD: CAMS youth (N = 488; 74% ≤12 years of age) with DSM-IV separation, generalized, or social anxiety disorder were randomized to 12 weeks of cognitive-behavioral therapy (CBT), sertraline (SRT), CBT+SRT (COMB), or medication management/pill placebo (PBO). Responders attended 6 monthly booster sessions in their assigned treatment arm; youth in COMB and SRT continued on their medication throughout this period. Efficacy of COMB, SRT, and CBT (n = 412) was assessed at 24 and 36 weeks postrandomization. Youth randomized to PBO (n = 76) were offered active CAMS treatment if nonresponsive at week 12 or over follow-up and were not included here. Independent evaluators blind to study condition assessed anxiety severity, functioning, and treatment response. Concomitant treatments were allowed but monitored over follow-up. RESULTS: The majority (\u3e80%) of acute responders maintained positive response at both weeks 24 and 36. Consistent with acute outcomes, COMB maintained advantage over CBT and SRT, which did not differ, on dimensional outcomes; the 3 treatments did not differ on most categorical outcomes over follow-up. Compared to COMB and CBT, youth in SRT obtained more concomitant psychosocial treatments, whereas those in SRT and CBT obtained more concomitant combined (medication plus psychosocial) treatment. CONCLUSIONS: COMB maintained advantage over CBT and SRT on some measures over follow-up, whereas the 2 monotherapies remained indistinguishable. The observed convergence of COMB and monotherapy may be related to greater use of concomitant treatment during follow-up among youth receiving the monotherapies, although other explanations are possible. Although outcomes were variable, most CAMS-treated youth experienced sustained treatment benefit. Clinical trial registration information-Child and Adolescent Anxiety Disorders (CAMS); URL: http://clinicaltrials.gov. Unique identifier: NCT00052078