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

Abstract

The risk-benefit balance of pharmacological treatment for children and adolescents with ADHD and the factors that moderate this relationship are unclear. 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. Sixty-three studies were included. Ten drugs were investigated, with atomoxetine and methylphenidate the most frequently studied. RPCCTs had mostly a short duration (7.9weeks). 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. 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.