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Meta-analysis supports short-term methylphenidate, amphetamines for children, adults with ADHD

Methylphenidate for children and amphetamines for adults were the preferred first-choice medications for the short-term treatment of ADHD, according to results from a network meta-analysis and systematic review.

“Even though recommended in clinical guidelines, the efficacy and safety of ADHD medications remains controversial,” Samuele Cortese, MD, from the Center for Innovation in Mental Health, University of Southampton, England, and the division of psychiatry and applied psychology, University of Nottingham School of Medicine, and colleagues wrote in The Lancet Psychiatry. “Previous network meta-analyses in ADHD have focused on either children and adolescents or adults only, have typically compared only a few drugs, or have addressed exclusively the safety of treatments.”

To comprehensively determine the efficacy and tolerability of oral medications for ADHD in children, teenagers and adults, the investigators searched clinical databases for double-blind, randomized controlled trials comparing amphetamines, atomoxetine, bupropion, clonidine, guanfacine, methylphenidate and modafinil with each other or placebo.

Using pairwise and network meta-analysis with random effects to estimate summary ORs and standardized mean differences, researchers examined the change in severity of ADHD symptoms based on teachers’ and clinicians’ ratings and the proportion of patients who dropped out of studies due to adverse effects at 12 weeks, 26 weeks and 52 weeks.

In total, 81 randomized-controlled trials in children and adolescents, 51 in adults and one in both were included in this study. Efficacy analysis at close to 12 weeks was based on data from 10,068 children and teens and 8,131 adults, and tolerability analysis was based on data from 11,018 children and teens and 5,362 adults.

The results supported methylphenidate in pediatric populations and amphetamines in adults as the first pharmacological choice for short-term ADHD treatment. In adults, amphetamines were also as well-tolerated as methylphenidate and were the only compounds with better acceptability than placebo. In children and teenagers, amphetamines were marginally better than methylphenidate based on clinicians’ ratings; however, methylphenidate showed better acceptability than placebo and superior tolerability to placebo.

For core symptoms of ADHD rated by clinicians in children and teenagers at around 12 weeks, all included ADHD medications outperformed placebo. Based on teachers’ ratings however, only methylphenidate and modafinil were more efficacious than placebo. According to clinicians’ ratings, treatment with amphetamines, methylphenidate, bupropion and atomoxetine were superior to placebo in adults.

In tolerability analysis, placebo outperformed amphetamines in pediatric populations (OR = 2.3; 95% CI, 1.36-3.89) and adults (OR = 3.26, 95% CI, 1.54-6.92). Guanfacine was inferior to placebo in children and adolescents only (OR = 2.64), whereas atomoxetine (OR = 2.33) methylphenidate (OR = 2.39) and modafinil (OR = 4.01) were inferior to placebo in adults only.

There were not enough data for the 26-week and 52-week timepoints, according to the authors.

“Our findings represent the best currently available evidence base (not constrained by local costs and licensing) to inform future guidelines internationally and shared decision-making between patients, carers and clinicians, when a balance has to be made between efficacy and tolerability of ADHD medications,” Cortese and colleagues concluded.

The meta-analysis derived data that support short-term ADHD drug use, basic guidelines about first-line medications based on age, and limited data for treatment duration; thus, more research is needed, Anne Arnett, PhD, and Mark Stein, PhD, of the University of Washington, wrote in a related comment.

“These results — and particularly limitations of the data obtained — call for future research that translates directly to clinical practice,” they wrote. “Ultimately, this need will require funding agencies to support longitudinal and active comparison designs, attention to sequencing and combining pharmacological and behavioral interventions, and development of big datasets that permit identification of patient predictors, which have thus far remained elusive.” – by Savannah Demko

Disclosures: Cortese reports reimbursement for travel and accommodation expenses from the Association for Child and Adolescent Central Health and from Healthcare Convention. Please see the study for all other authors’ relevant financial disclosures. Arnett and Stein report no relevant financial disclosures.