https://paigeconnors.files.wordpress.com/2013/12/whittington-et-al_2004.pdf

Selective serotonin reuptake inhibitors in childhood depression: systematic review of published versus unpublished data.

ContextThe US Food and Drug Administration (FDA) has issued warnings that use of antidepressant medications poses a small but significantly increased risk of suicidal ideation/suicide attempt for children and adolescents.ObjectiveTo assess the efficacy and risk of reported suicidal ideation/suicide attempt of antidepressants for treatment of pediatric major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and non-OCD anxiety disorders.Data Sources and Study SelectionPubMed (1988 to July 2006), relevant US and British regulatory agency reports, published abstracts of important scientific meetings (1998-2006), clinical trial registries, and information from authors. Studies were published and unpublished randomized, placebo-controlled, parallel-group trials of second-generation antidepressants (selective serotonin reuptake inhibitors, nefazodone, venlafaxine, and mirtazapine) in participants younger than 19 years with MDD, OCD, or non-OCD anxiety disorders.Data ExtractionInformation was extracted on study characteristics, efficacy outcomes, and spontaneously reported suicidal ideation/suicide attempt.Data SynthesisTwenty-seven trials of pediatric MDD (n = 15), OCD (n = 6), and non-OCD anxiety disorders (n = 6) were selected, and risk differences for response and for suicidal ideation/suicide attempt estimated by random-effects methods. Pooled risk differences in rates of primary study-defined measures of responder status significantly favored antidepressants for MDD (11.0%; [95% confidence interval {CI}, 7.1% to 14.9%]), OCD (19.8% [95% CI, 13.0% to 26.6%), and non-OCD anxiety disorders (37.1% [22.5% to 51.7%]), corresponding to a number needed to treat (NNT) of 10 (95% CI, 7 to 15), 6 (4 to 8), and 3 (2 to 5), respectively. While there was increased risk difference of suicidal ideation/suicide attempt across all trials and indications for drug vs placebo (0.7%; 95% CI, 0.1% to 1.3%) (number needed to harm, 143 [95% CI, 77 to 1000]), the pooled risk differences within each indication were not statistically significant: 0.9% (95% CI, −0.1% to 1.9%) for MDD, 0.5% (−1.2% to 2.2%) for OCD, and 0.7% (−0.4% to 1.8%) for non-OCD anxiety disorders. There were no completed suicides. Age-stratified analyses showed that for children younger than 12 years with MDD, only fluoxetine showed benefit over placebo. In MDD trials, efficacy was moderated by age, duration of depression, and number of sites in the treatment trial.ConclusionsRelative to placebo, antidepressants are efficacious for pediatric MDD, OCD, and non-OCD anxiety disorders, although the effects are strongest in non-OCD anxiety disorders, intermediate in OCD, and more modest in MDD. Benefits of antidepressants appear to be much greater than risks from suicidal ideation/suicide attempt across indications, although comparison of benefit to risk varies as a function of indication, age, chronicity, and study conditions.

https://jamanetwork.com/journals/jama/articlepdf/206656/jrv70005_1683_1696.pdf

Clinical Response and Risk for Reported Suicidal Ideation and Suicide Attempts in Pediatric Antidepressant Treatment: A Meta-analysis of Randomized Controlled Trials

This practice parameter describes the epidemiology, clinical picture, differential diagnosis, course, risk factors, and pharmacological and psychotherapy treatments of children and adolescents with major depressive or dysthymic disorders. Side effects of the antidepressants, particularly the risk of suicidal ideation and behaviors are discussed. Recommendations regarding the assessment and the acute, continuation, and maintenance treatment of these disorders are based on the existent scientific evidence as well as the current clinical practice. J. Am. Acad. Child Adolesc. Psychiatry, 2007; 46(11):1503Y1526. Key Words: major depressive disorder, dysthymic disorder, evaluation, treatment, antidepressants, selective serotonin reuptake inhibitors, psychotherapy, practice parameter. Depressive disorders are often familial recurrent illnesses associated with increased psychosocial morbidity and mortality. Early identification and effective treatment may reduce the impact of depression on the family, social, and academic functioning in youths and may reduce the risk of suicide, substance abuse, and persistence of depressive disorders into adulthood. Evidencesupported treatment interventions have emerged in psychotherapy and medication treatment of childhood depressive disorders that can guide clinicians to improve outcomes in this population.

https://aacap.org/app_themes/aacap/docs/practice_parameters/depressive_disorders_practice_parameter.pdf

Practice Parameter for the Assessment and Treatment of Children and Adolescents With Depressive Disorders

https://www.zora.uzh.ch/id/eprint/156991/1/Cortese_et_al_2018_Comparative_efficacy_and_tolerability_of_medications_formain.pdf

Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis

Major depression affects 3 to 5 percent of children and adolescents. Depression negatively impacts growth and development, school performance, and peer or family relationships and may lead to suicide. Biomedical and psychosocial risk factors include a family history of depression, female sex, childhood abuse or neglect, stressful life events, and chronic illness. Diagnostic criteria for depression in children and adolescents are essentially the same as those for adults; however, symptom expression may vary with developmental stage, and some children and adolescents may have difficulty identifying and describing internal mood states. Safe and effective treatment requires accurate diagnosis, suicide risk assessment, and use of evidence-based therapies. Current literature supports use of cognitive behavior therapy for mild to moderate childhood depression. If cognitive behavior therapy is unavailable, an antidepressant may be considered. Antidepressants, preferably in conjunction with cognitive behavior therapy, may be considered for severe depression. Tricyclic antidepressants generally are ineffective and may have serious adverse effects. Evidence for the effectiveness of selective serotonin reuptake inhibitors is limited. Fluoxetine is approved for the treatment of depression in children eight to 17 years of age. All antidepressants have a black box warning because of the risk of suicidal behavior. If an antidepressant is warranted, the risk/benefit ratio should be evaluated, the parent or guardian should be educated about the risks, and the patient should be monitored closely (i.e., weekly for the first month and every other week during the second month) for treatment-emergent suicidality. Before an antidepressant is initiated, a safety plan should be in place. This includes an agreement with the patient and the family that the patient will be kept safe and will contact a responsible adult if suicidal urges are too strong, and assurance of the availability of the treating physician or proxy 24 hours a day to manage emergencies.

Childhood and adolescent depression.

ContextThe efficacy, safety, and tolerability of selective serotonin reuptake
inhibitors (SSRIs) in the treatment of adults with major depressive disorder
(MDD) are well established. Comparatively few data are available on the effects
of SSRIs in depressed children and adolescents.ObjectiveTo evaluate the efficacy and safety of sertraline compared with placebo
in treatment of pediatric patients with MDD.Design and SettingTwo multicenter randomized, double-blind, placebo-controlled trials
were conducted at 53 hospital, general practice, and academic centers in the
United States, India, Canada, Costa Rica, and Mexico between December 1999
and May 2001 and were pooled a priori.ParticipantsThree hundred seventy-six children and adolescents aged 6 to 17 years
with Diagnostic and Statistical Manual of Mental Disorders,
Fourth Edition–defined MDD of at least moderate severity.InterventionPatients were randomly assigned to receive a flexible dosage (50-200
mg/d) of sertraline (n = 189) or matching placebo tablets (n = 187) for 10
weeks.Main Outcome MeasuresChange from baseline in the Children's Depression Rating Scale–Revised
(CDRS-R) Best Description of Child total score and reported adverse events.ResultsSertraline-treated patients experienced statistically significantly
greater improvement than placebo patients on the CDRS-R total score (mean
change at week 10, –30.24 vs –25.83, respectively; P = .001; overall mean change, –22.84 vs –20.19, respectively; P = .007). Based on a 40% decrease in the adjusted CDRS-R
total score at study end point, 69% of sertraline-treated patients compared
with 59% of placebo patients were considered responders (P = .05). Sertraline treatment was generally well tolerated. Seventeen
sertraline-treated patients (9%) and 5 placebo patients (3%) prematurely discontinued
the study because of adverse events. Adverse events that occurred in at least
5% of sertraline-treated patients and with an incidence of at least twice
that in placebo patients included diarrhea, vomiting, anorexia, and agitation.ConclusionThe results of this pooled analysis demonstrate that sertraline is an
effective and well-tolerated short-term treatment for children and adolescents
with MDD.

https://jamanetwork.com/journals/jama/articlepdf/197174/JOC22408.pdf

Efficacy of sertraline in the treatment of children and adolescents with major depressive disorder: two randomized controlled trials.

Efficacy of Sertraline in the Treatment of Children and Adolescents With Major Depressive Disorder

Objective: The aim of this study was to evaluate the efficacy, safety, and tolerability of SHP465 mixed amphetamine salts (MAS) in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). Methods: This randomized, double-blind dose-optimization study enrolled children and adolescents (6–17 years) meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision ADHD criteria and having baseline ADHD Rating Scale IV (ADHD-RS-IV) total scores ≥28. Participants were randomized 1:1 to placebo or dose-optimized SHP465 MAS (12.5–25 mg) for 4 weeks. Total score change (baseline to week 4) on the ADHD-RS-IV (primary endpoint) and the Clinical Global Impressions-Improvement (CGI-I) scale score at week 4 (key secondary endpoint) were assessed using linear mixed-effects models for repeated measures. Safety and tolerability assessments (secondary endpoints) included treatment-emergent adverse events (TEAEs) and vital sign changes. Results: Of 264 randomized pa...

SHP465 Mixed Amphetamine Salts in the Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents: Results of a Randomized, Double-Blind Placebo-Controlled Study.

Michael S. Greenbaum

Papers

Efficacy of sertraline in the treatment of children and adolescents with major depressive disorder: two randomized controlled trials.

Efficacy of Sertraline in the Treatment of Children and Adolescents With Major Depressive Disorder

SHP465 Mixed Amphetamine Salts in the Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents: Results of a Randomized, Double-Blind Placebo-Controlled Study.