Discontinuation of pharmacological treatment of children and adolescents with attention deficit hyperactivity disorder: meta-analysis of 63 studies enrolling 11,788 patients

• Published in: Psychopharmacology Vol. 234; no. 17; pp. 2657 - 2671
• Main Authors: Riera, M., Castells, X., Tobias, A., Cunill, R., Blanco, L., Capellà, D.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.09.2017; Springer; Springer Nature B.V
• Subjects: Adolescent; Adolescents; Atomoxetine Hydrochloride - therapeutic use; Attention Deficit Disorder with Hyperactivity - drug therapy; Attention deficit hyperactivity disorder; Bias; Biomedical and Life Sciences; Biomedicine; Central Nervous System Stimulants - therapeutic use; Child; Child & adolescent psychiatry; Children; Clinical trials; Comorbidity; Drug therapy; Female; Humans; Male; Meta-analysis; Methylphenidate; Methylphenidate - therapeutic use; Neurosciences; Original Investigation; Patient outcomes; Patients; Pharmacology/Toxicology; Psychiatry; Psychopharmacology; Systematic review; Treatment Outcome; Withholding Treatment; Meta-regression; Discontinuation; Attention deficit hyperactivity disorder; Efficacy; Safety; Controlled clinical trial; Meta-analysis
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-017-4662-1

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.