M Riera1,2, X Castells3, A Tobias4, R Cunill5, L Blanco6, D Capellà6. 1. Ethics Committee of University Hospital of Girona Dr. Josep Trueta, Girona, Spain. 2. Girona Biomedical Research Institute (IdIBGi), Girona, Spain. 3. Pharmacology Unit, TransLab Research Group, Department of Medical Sciences, Universitat de Girona, C/ Emili Grahit, 77, 17003, Girona, Spain. xavier.castells@udg.edu. 4. Clinical Institute of Environmental Assessment and Water Research (IDAEA), Spanish Council for Scientific Research (CSIC), Barcelona, Spain. 5. Parc Sanitari Sant Joan de Déu-Numància, Parc Sanitari Sant Joan de Déu, Barcelona, Spain. 6. Pharmacology Unit, TransLab Research Group, Department of Medical Sciences, Universitat de Girona, C/ Emili Grahit, 77, 17003, Girona, Spain.
Abstract
BACKGROUND: The risk-benefit balance of pharmacological treatment for children and adolescents with ADHD and the factors that moderate this relationship are unclear. METHODS: A systematic review and meta-analysis of randomised, placebo-controlled clinical trials (RPCCTs) investigating the efficacy of pharmacological treatment in children or adolescents with ADHD was carried out. Meta-analysis of treatment discontinuation, clinician-, parent- and teacher-rated efficacy and adverse events was performed. The effect of covariates was studied. RESULTS: Sixty-three studies were included. Ten drugs were investigated, with atomoxetine and methylphenidate the most frequently studied. RPCCTs had mostly a short duration (7.9 weeks). All-cause treatment discontinuation was lower with pharmacological treatment than placebo (OR = 0.68). Pharmacological treatment was more efficacious than placebo independently of the rater (clinician, standardised mean difference (SMD) 0.74; parent, SMD = 0.63; or teacher, SMD = 0.75). Evidence of publication bias was found for clinician-rated efficacy, especially in industry-sponsored RPCCT. Psychostimulants showed a higher efficacy and were associated with a better outcome on treatment discontinuation than non-stimulant drugs. Efficacy was smaller in RPCCTs for which a psychiatric comorbid disorder was an inclusion criterion, was larger in studies with a commercial sponsorship and showed a negative association with treatment length. CONCLUSIONS: In the short term, pharmacological treatment provides moderate-high symptom relief, is safe and shows lower treatment discontinuation than placebo, suggesting a suitable risk-benefit balance, particularly with psychostimulants. The efficacy is lower in patients with a comorbid psychiatric disorder and should be assessed periodically, as it appears to reduce over time. Publication bias of clinician-rated efficacy in studies with a commercial sponsor is suggested.
BACKGROUND: The risk-benefit balance of pharmacological treatment for children and adolescents with ADHD and the factors that moderate this relationship are unclear. METHODS: A systematic review and meta-analysis of randomised, placebo-controlled clinical trials (RPCCTs) investigating the efficacy of pharmacological treatment in children or adolescents with ADHD was carried out. Meta-analysis of treatment discontinuation, clinician-, parent- and teacher-rated efficacy and adverse events was performed. The effect of covariates was studied. RESULTS: Sixty-three studies were included. Ten drugs were investigated, with atomoxetine and methylphenidate the most frequently studied. RPCCTs had mostly a short duration (7.9 weeks). All-cause treatment discontinuation was lower with pharmacological treatment than placebo (OR = 0.68). Pharmacological treatment was more efficacious than placebo independently of the rater (clinician, standardised mean difference (SMD) 0.74; parent, SMD = 0.63; or teacher, SMD = 0.75). Evidence of publication bias was found for clinician-rated efficacy, especially in industry-sponsored RPCCT. Psychostimulants showed a higher efficacy and were associated with a better outcome on treatment discontinuation than non-stimulant drugs. Efficacy was smaller in RPCCTs for which a psychiatric comorbid disorder was an inclusion criterion, was larger in studies with a commercial sponsorship and showed a negative association with treatment length. CONCLUSIONS: In the short term, pharmacological treatment provides moderate-high symptom relief, is safe and shows lower treatment discontinuation than placebo, suggesting a suitable risk-benefit balance, particularly with psychostimulants. The efficacy is lower in patients with a comorbid psychiatric disorder and should be assessed periodically, as it appears to reduce over time. Publication bias of clinician-rated efficacy in studies with a commercial sponsor is suggested.
Authors: Mark Wolraich; Lawrence Brown; Ronald T Brown; George DuPaul; Marian Earls; Heidi M Feldman; Theodore G Ganiats; Beth Kaplanek; Bruce Meyer; James Perrin; Karen Pierce; Michael Reiff; Martin T Stein; Susanna Visser Journal: Pediatrics Date: 2011-10-16 Impact factor: 7.124
Authors: Eugenia Oviedo-Joekes; Suzanne Brissette; David C Marsh; Pierre Lauzon; Daphne Guh; Aslam Anis; Martin T Schechter Journal: N Engl J Med Date: 2009-08-20 Impact factor: 91.245
Authors: J Graham; T Banaschewski; J Buitelaar; D Coghill; M Danckaerts; R W Dittmann; M Döpfner; R Hamilton; C Hollis; M Holtmann; M Hulpke-Wette; M Lecendreux; E Rosenthal; A Rothenberger; P Santosh; J Sergeant; E Simonoff; E Sonuga-Barke; I C K Wong; A Zuddas; H-C Steinhausen; E Taylor Journal: Eur Child Adolesc Psychiatry Date: 2010-11-03 Impact factor: 4.785