Oxford, UK—A number of medications are available for treatment of attention-deficit hyperactivity disorder (ADHD), but which ones are most effective and safest for short-term treatment of children and adults?

A new study in The Lancet Psychiatry journal provides an answer to that question. University of Oxford–led researchers cite evidence from a network meta-analysis and systematic review comparing the effectiveness and safety of seven ADHD drugs against placebo that determined that methylphenidate for children and amphetamines for adults are the best options.

The effectiveness and adverse effects of the following drugs were analyzed in the study:
• Amphetamines, including lisdexamfetamine
• Atomoxetine
• Bupropion
• Clonidine
• Guanfacine
• Methylphenidate
• Modafinil

The medications were compared with each other or with placebo over 12 weeks of treatment. The research did not include antipsychotic drugs or antidepressants, which often are prescribed for ADHD but do not treat ADHD core symptoms.

To gather information, the study team conducted a literature search for published and unpublished randomized, double-blind, controlled trials for the ADHD drugs, contacting study authors and drug manufacturers if additional information was required. Primary outcomes were defined as efficacy (i.e., change in severity of ADHD core symptoms based on teachers’ and clinicians’ ratings) and tolerability (i.e., proportion of patients who dropped out of studies because of side effects) at timepoints closest to 12 weeks, 26 weeks, and 52 weeks.

Ultimately, the meta-analysis included 133 randomized, double-blind, controlled trials—81 in children and adolescents, 51 in adults, and one in both. Analysis of efficacy closest to 12 weeks was based on 10,068 children and adolescents and 8,131 adults who participated in the trials, while the analysis of tolerability was based on 11,018 children and adolescents and 5,362 adults.

The study found that, for ADHD core symptoms rated by clinicians in children and adolescents closest to 12 weeks, all included drugs were superior to placebo (e.g., standardized mean difference [SMD] -1.02, 95% CI -1.19 to -0.85 for amphetamines, -0.78, -0.93 to -0.62 for methylphenidate, -0.56, -0.66 to -0.45 for atomoxetine).

On the other hand, for available comparisons based on teachers’ ratings, only methylphenidate (SMD -0.82, 95% CI -1.16 to -0.48) and modafinil (-0.76, -1.15 to -0.37), appeared to be more effective than placebo.

For adults, based on clinician ratings, amphetamines (SMD -0.79, 95% CI -0.99 to -0.58); methylphenidate (-0.49, -0.64 to -0.35); bupropion (-0.46, -0.85 to -0.07); and atomoxetine (-0.45, -0.58 to -0.32), but not modafinil (0.16, -0.28 to 0.59), were superior to placebo, the study authors report.

“With respect to tolerability, amphetamines were inferior to placebo in both children and adolescents (odds ratio [OR] 2·30, 95% CI 1·36–3·89) and adults (3·26, 1·54–6·92); guanfacine was inferior to placebo in children and adolescents only (2·64, 1·20–5·81); and atomoxetine (2·33, 1·28–4·25), methylphenidate (2·39, 1·40–4·08), and modafinil (4·01, 1·42–11·33) were less well tolerated than placebo in adults only,” the researchers point out.

“Medication can be an important tool for people with ADHD, and our study illustrates that in the short term, these can be effective and safe treatment options for children, adolescents and adults,” explained Andrea Cipriani, MD, PhD, of the University of Oxford.

“It’s important to note that the data available only allow us to compare the effectiveness at 12 weeks, when we know that both children and adults can be on these medications for longer. More research is needed into the long-term effects of medication.”
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