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

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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.

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Authors and Affiliations

  1. Ethics Committee of University Hospital of Girona Dr. Josep Trueta, Girona, Spain

    M. Riera

  2. Girona Biomedical Research Institute (IdIBGi), Girona, Spain

    M. Riera

  3. Pharmacology Unit, TransLab Research Group, Department of Medical Sciences, Universitat de Girona, C/ Emili Grahit, 77, 17003, Girona, Spain

    X. Castells, L. Blanco & D. Capellà

  4. Clinical Institute of Environmental Assessment and Water Research (IDAEA), Spanish Council for Scientific Research (CSIC), Barcelona, Spain

    A. Tobias

  5. Parc Sanitari Sant Joan de Déu-Numància, Parc Sanitari Sant Joan de Déu, Barcelona, Spain

    R. Cunill

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  1. M. Riera
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  2. X. Castells
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  3. A. Tobias
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  4. R. Cunill
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Correspondence to X. Castells.

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Riera, M., Castells, X., Tobias, A. et al. Discontinuation of pharmacological treatment of children and adolescents with attention deficit hyperactivity disorder: meta-analysis of 63 studies enrolling 11,788 patients. Psychopharmacology 234, 2657–2671 (2017). https://doi.org/10.1007/s00213-017-4662-1

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