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Treatment of Depression in Children and Adolescents: A Systematic Review. Comparative Effectiveness Review No. 224

Author/s: 
Viswanathan, M, Kennedy, SM, McKeeman, J, Christian, R, Coker-Schwimmer, Cook Middleton, Bann, C, Lux, L, Randolph, Forman-Hoffman, V

Background. Depressive disorders can affect long-term mental and physical health functioning among children and adolescents, including increased risk of suicide. Despite access to several nonpharmacological, pharmacological, and combined treatment options for childhood depression, clinicians contend with sparse evidence and are concerned about harms associated with treatment.

Methods. We conducted a systematic review to evaluate the efficacy, comparative effectiveness, and moderators of benefits and harms of available nonpharmacological and pharmacological treatments for children and adolescents with a confirmed diagnosis of a depressive disorder (DD)—major depressive disorder (MDD), persistent depressive disorder (previously termed dysthymia) or DD not otherwise specified. We searched five databases and other sources for evidence available from inception to May 29, 2019, dually screened the results, and analyzed eligible studies.

Results. We included in our analyses data from 60 studies (94 articles) that met our review eligibility criteria. For adolescents (study participants’ ages range from 12 to 18 years) with MDD, cognitive behavioral therapy (CBT), fluoxetine, escitalopram, and combined fluoxetine and CBT may improve depressive symptoms (1 randomized controlled trial [RCT] each, n ranges from 212 to 311); whether the magnitude of improvement is clinically significant is unclear. Among adolescents or children with MDD, CBT plus medications (8–17 years) may be associated with lower rates of relapse (1 RCT [n = 121]). In the same population (6–17 years), selective serotonin reuptake inhibitors (SSRIs) may be associated with improved response (7 RCTs [n = 1,525]; risk difference [RD], 72/1,000 [95% confidence interval (CI), 2 to 24], I2 = 9%) and functional status (5 RCTs [n = 941]; standardized mean difference, 0.16 [95% CI, 0.03 to 0.29]; I2 = 0%). For adolescents or children with any DD (7–18 years), CBT or family therapy may be associated with improvements in symptoms, response, or functional status (1 RCT each, n ranges from 64 to 99). Among children with any DD (7–12 years), family-based interpersonal therapy may be associated with improved symptoms (1 RCT, n = 38). Psychotherapy trials did not report harms. SSRIs may be associated with a higher risk of serious adverse events among adolescents or children with MDD (7–18 years; 9 RCTs [n = 2,206]; RD, 20/1,000 [95% CI, 1 to 440]; I2, 4%) and with a higher risk of withdrawal due to adverse events among adolescents with MDD (12–18 years; 4 RCTs [n = 1,296], RD, 26/1,000 [95% CI, 6 to 45]; I2, 0%). Paroxetine (1 RCT [n = 180]) may be associated with a higher risk of suicidal ideation or behaviors among adolescents with MDD (12–18 years). Evidence was insufficient to judge the risk of suicidal ideation or behavior for other SSRIs for adolescents and children with MDD or other DD (7–18 years) (10 RCTs [n = 2,368]; relative risk, 1.14 [95% CI, 0.89 to 1.45]; I2, 8%). However, this report excluded data on inpatients and those without depressive disorders, whom the Food and Drug Administration included in finding an increased risk of suicidality for all antidepressants across all indications.

Conclusion. Efficacious treatments exist for adolescents with MDD. SSRIs may be associated with increased withdrawal and serious adverse events. No evidence on harms of psychotherapy were identified.

Keywords 
children adolescent child depression treatment cognitive behavioral therapy selective serotonin reuptake inhibitors

Attention Deficit Hyperactivity Disorder: Diagnosis and Treatment in Children and Adolescents Comparative Effectiveness Review No. 203

Author/s: 
Kemper, AR, Maslow, GR, Hill, S, Namdari, B, Allen LaPoint, NM, Goode, AP, Coeytaux, RR, Befus, D, Kosinski, AS, Bowen, SE, McBroom, AJ, Lallinger, KR, Sanders, GD

Objectives. Attention deficit hyperactivity disorder (ADHD) is a common pediatric neurobehavioral disorder often treated in the primary care setting. This systematic review updates and extends two previous Agency for Healthcare Research and Quality (AHRQ) systematic evidence reviews and focuses on the comparative effectiveness of methods to establish the diagnosis of ADHD, updates the comparative effectiveness of pharmacologic and nonpharmacologic treatments, and evaluates different monitoring strategies in the primary care setting for individuals from birth through 17 years of age.

Data sources. We searched PubMed®, Embase®, PsycINFO®, and the Cochrane Database of Systematic Reviews for relevant English-language studies published from January 1, 2011, through November 7, 2016.

Review methods. Two investigators screened each abstract and full-text article for inclusion, abstracted the data, and performed quality ratings and evidence grading. Random-effects models were used to compute summary estimates of effects when sufficient data were available for meta-analysis.

Results. Evidence was contributed from 103 articles describing 90 unique studies. Twenty-one studies related to diagnosis, 69 studies related to treatment, and no studies were identified on monitoring. The Attention and Executive Function Rating Inventory and Childhood Executive Functioning Inventory performed better than the Cambridge Neuropsychological Test Automated Battery for the diagnosis of ADHD for ages 7–17 years (strength of evidence [SOE]=low). Evidence was insufficient on the use of electroencephalography (EEG) or neuroimaging to establish the diagnosis of ADHD for ages 7–17 years. No studies directly assessed the harms to children labeled as having ADHD. Limited additional evidence published since the original 2011 report was available on ADHD medications approved by the Food and Drug Administration (FDA) compared with placebo or compared to different FDA-approved ADHD medications (SOE=insufficient). For atomoxetine and methylphenidate, the most commonly reported adverse events were somnolence and mild gastrointestinal problems. Atomoxetine had slightly higher gastrointestinal effects than methylphenidate (SOE=low). Cognitive behavioral therapy improved ADHD symptoms (SOE=low). Child or parent training improved ADHD symptoms (SOE=moderate) but made no difference in academic performance (SOE=low). Omega-3/6 fatty acid supplementation made no difference in ADHD symptoms (SOE=moderate). Across all treatments, little evidence was reported on the risk of serious adverse events, including cardiovascular risk.

Conclusions. The 2011 AHRQ systematic review highlighted the benefit of psychostimulants for children 6–12 years of age with ADHD for up to 24 months and found that adding psychosocial/behavioral interventions to psychostimulants is more effective than psychosocial/behavioral interventions alone for children with ADHD and oppositional defiant disorder. This targeted update found insufficient evidence regarding new approaches to the diagnosis (e.g., EEGs, neuroimaging). Little is known about the impact of being labeled as having ADHD. Although cognitive behavioral therapy or child or parent training may decrease symptoms of ADHD, more information is needed regarding the relative benefit of these approaches compared to, or combined with, medication treatment. Omega-3/6 supplementation does not appear to improve ADHD outcomes. No information was identified regarding the optimal strategy for monitoring after diagnosis.

Keywords 
ADHD attention deficit disorder with hyperactivity ADHD treatment children adolescent
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