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Methylphenidate (Ritalin) may be a first-choice attention-deficit/hyperactivity disorder (ADHD) medication for kids, while amphetamines may be preferred for adults, a large-scale meta-analysis affirmed.

Across the 133 trials, all ADHD medications were superior to placebo with regards to 12-week efficacy in children and adolescents based on clinician ratings for the change in ADHD symptoms, reported Andrea Cipriani, MD, PhD, of the University of Oxford, and colleagues in . The standardized mean differences were:

• Amphetamines: -1.02 (95% CI -1.19 to -0.85)
• Atomoxetine (Strattera): -0.56 (95% CI -0.66 to -0.45)
• Bupropion (Wellbutrin): -0.96 (95% CI -1.69 to –0.22)
• Clonidine (Catapres): -0.71 (95% CI -1.17 to -0.24)
• Guanfacine (Intuniv): -0.67 (95% CI -0.85 to -0.50)
• Methylphenidate: -0.78 (95% CI -0.93 to -0.62)
• Modafinil (Provigil): -0.62 (95% CI -0.84 to -0.41)

However, the other primary efficacy endpoint for kids, based on teacher's rating of kids' ADHD symptoms, showed only methylphenidate (standardized mean difference -0.82, 95% CI -1.16 to -0.48) and modafinil (-0.76, 95% CI -1.15 to -0.37) superior to placebo.

In a separate look at adult patients, all treatments except for modafinil worked better than placebo after 12 weeks of therapy, based on clinicians' ratings of the patients' ADHD symptoms:

• Amphetamines: mean difference -0.79 (95% CI -0.99 to -0.58)
• Atomoxetine: -0.45 (95% CI -0.58 to -0.32)
• Bupropion: -0.46 (95% CI -0.85 to -0.07)
• Methylphenidate: -0.49 (95% CI -0.64 to -0.35)

"The results support a moderating effect of age on first-line medication choice, consistent with current use patterns in the USA, with greatest support for methylphenidate in children and adolescents and amphetamine formulations in adults," concluded Anne Arnett, PhD, and Mark Stein, PhD, both of the University of Washington in Seattle, in an .

clinical practice guidelines recommend methylphenidate as the first-line oral treatment following behavioral therapy for preschool-aged children. As for older kids, those guidelines are less concrete, simply recommending an FDA-approved medication for adolescents with ADHD.

The British also recommend methylphenidate as the first choice in children and adolescents but methylphenidate or lisdexamfetamine as first choice in adults, the researchers noted, which also factored in "considerations on costs and licence and flexibility of formulations."

The meta-analysis for 12-week medication efficacy was based on records from 10,068 children and adolescents and 8,131 adults, while the tolerability analysis included 11,018 youth and 5,362 adults. The systematic review looked at trials that assessed oral monotherapy options for ADHD, which included amphetamines and lisdexamfetamine, atomoxetine, bupropion, clonidine, guanfacine, methylphenidate and dexmethylphenidate, as well as modafinil.

Among children and adolescents, the odds of dropping out over adverse events was higher for both amphetamines (OR 2.30, 95% CI 1.36-3.89) and guanfacine (2.64, 95% CI 1.20-5.81) compared with placebo.

Among adults with ADHD, amphetamines were also less tolerable than placebo by the same measure (OR 3.26, 95% CI 1.54-6.92), despite their high efficacy. Drop out due to side effects was also more common with atomoxetine (OR 2.33, 95% CI 1.28-4.25), methylphenidate (OR 2.39, 95% CI 1.40-4.08), and modafinil (OR 4.01, 95% CI 1.42-11.33).

The analysis "synthesized crucial information for development of guidelines that will inform clinical decision-making," the editorialists noted.

"This analysis directly addresses the public health approach to pharmacological intervention and confirms the robust short-term efficacy of ADHD medications, although not all medications had the same effects," they wrote, noting that the tolerability analysis showed how close monitoring of blood pressure and weight changes is necessary not only with stimulants but with atomoxetine as well.

Nevertheless, limitations of the meta-analysis include the "paucity" of longitudinal and active-comparator studies, Arnett and Stein pointed out, calling for future studies to address this. Another weakness was that the included studies tended not to differentiate between medication efficacy in younger children and in teenagers, the editorialists added.