ADHD Medications Compared for Efficacy, Tolerability in Children and Adults

The authors highlighted the need for longer-term studies
The authors highlighted the need for longer-term studies

A meta-analysis and systematic review of 133 randomized-controlled trials assessing attention-deficit hyperactivity disorder (ADHD) medications found that methylphenidate in children/adolescents and amphetamines in adults were the most effective and safe short-term treatments. The full findings were published in The Lancet Psychiatry.

The 7 treatments included in the review were amphetamines (including lisdexamfetamine), atomoxetine, bupropion, clonidine, guanfacine, methylphenidate, and modafinil. Antipsychotics and antidepressants were not included as they do not treat core symptoms. The primary outcomes were efficacy, as assessed by change in severity of ADHD core symptoms based on teacher/clinician ratings, and tolerability, as measured by the proportion of patients who dropped out of studies due to adverse effects at points closest to weeks 12, 26, and 52. 

The efficacy analysis included 10,068 children/adolescents and 8131 adults; the tolerability analysis included 11,018 children/adolescents and 5362 adults. Clinicians rated symptoms for adults while clinicians and teachers rated symptoms for children. 

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Among children/adolescents, all drugs were superior to placebo for ADHD core symptoms closest to 12 weeks when rated by clinicians. However, teachers' ratings showed that only methylphenidate and modafinil were more effective vs placebo. Among adults, clinicians rated all treatments – except modafinil – more effective than placebo in controlling symptoms. Amphetamines were found to be more efficacious (clinicians' ratings) than modafinil, atomoxetine, and methylphenidate for all ages in head-to-head comparisons. 

With regard to tolerability, amphetamines were found to be less well tolerated in children/adolescents (odds ratio [OR] 2.30, 95% CI, 1.36–3.89) and adults (OR 3.26, 95% CI ,1.54–6.92) vs placebo. Moreover, amphetamines, methylphenidate, atomoxetine, and modafinil caused weight loss across all ages compared with placebo. An increase in systolic blood pressure was seen with amphetamines and atomoxetine in children/adolescents and with methylphenidate in adults.

The study did not include psychological therapies, though the authors say that these should be regularly discussed with patients and their family members or caregivers, and possibly offered before ADHD medications, if appropriate, especially for children and adolescents. 

The authors highlighted the need for longer-term studies as they did not find sufficient data for week 26 and week 52 timepoints. In general, the authors concluded that the evidence supports methylphenidate as first-line treatment of ADHD in children and adolescents and amphetamines as first-line in adults. 

For more information visit thelancet.com.