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Paper

Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis

Also known as Cortese et al. 2018, Cortese S et al. Comparative efficacy and tolerability of medications for ADHD, Lancet Psychiatry 2018, Comparative efficacy and tolerability of medications for ADHD

Network meta-analysis of 133 trials ranking ADHD drugs in children and adults (2018)

At a glance

Also on this page: Key facts · Links · Sources · Related pages

Why it matters

Key facts

Authors
Samuele Cortese, Nicoletta Adamo, Cinzia Del Giovane and 16 others; last author Andrea Cipriani1
Published
September 20181
Journal
The Lancet Psychiatry, vol. 5, issue 9, pp. 727–7381
DOI
10.1016/S2215-0366(18)30269-41
Design
Systematic review and network meta-analysis of double-blind RCTs; amphetamines, atomoxetine, bupropion, clonidine, guanfacine, methylphenidate, modafinil1
Sample
133 trials (81 in children and adolescents, 51 in adults, 1 both); efficacy based on 10,068 children and adolescents and 8,131 adults1
Main result
Clinician-rated symptoms in children vs placebo: SMD −1.02 amphetamines, −0.78 methylphenidate, −0.56 atomoxetine1
Adults
Amphetamines SMD −0.79, methylphenidate −0.49 vs placebo; modafinil no better than placebo1
Registration
PROSPERO CRD420140089761
Funding
Stichting Eunethydis and the NIHR Oxford Health Biomedical Research Centre1
Cited by
913 (Europe PMC count, October 2026)1

What it found

  1. All but one beat placebo2

    Every medication except modafinil in adults was more effective than placebo for short-term treatment.

  2. Children vs adults2

    Medications were less effective and less well tolerated in adults than in children and adolescents.

  3. Teachers see less1

    On teachers' ratings only methylphenidate (SMD −0.82) and modafinil (−0.76) beat placebo.

  4. Tolerability1

    Amphetamines caused more dropouts for side-effects than placebo at every age (OR 2.30 children, 3.26 adults).

  5. First choices1

    Weighing efficacy and safety: methylphenidate for children and adolescents, amphetamines for adults, short term.

Key ideas

  1. Network meta-analysis2

    Combines direct and indirect comparisons, so drugs never tested against each other can still be ranked.

  2. Unpublished data2

    The authors contacted study authors and manufacturers, cutting unclear risk-of-bias items from 63.5% to 35.2%.

  3. Who rates matters2

    Effect sizes ranged from moderate to high and varied with who rated the symptoms.

Criticism and limits

  1. Short term only2

    Too few trials ran to 26 or 52 weeks, so it informs only short-term choice of medication.

  2. Mostly indirect2

    Few head-to-head trials existed; many comparisons were indirect and rated low or very low confidence.

  3. Possible missing data2

    The search ran to April 2017, and missing trials cannot be ruled out.

Connections

Written by

  • Samuele Cortese
  • Andrea Cipriani

Related

Sources

  1. Cortese S et al. Comparative efficacy and tolerability of medications for ADHD, Lancet Psychiatry 2018 (Europe PMC) (opens europepmc.org)
  2. Cortese S et al. 2018, full text (PMC) (opens pmc.ncbi.nlm.nih.gov)

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