Objective

Neurocognitive deficits are at the heart of explanatory models of attention-deficit/hyperactivity disorder (ADHD), and lead to significant impairments in daily life. Determining the dosing effects of methylphenidate (MPH) on a broad range of neurocognitive functions and investigating possible impairing effects of high doses is therefore important.

Method

Placebo-controlled trials were included that investigated MPH dosing effects on neurocognitive functions in children and adolescents (aged 5–18 years) diagnosed with ADHD. Effect sizes (standardized mean differences [SMDs]) were calculated for different neurocognitive functions (baseline speed, variability in responding, nonexecutive memory and executive memory, inhibitory control, and cognitive flexibility) and, if available, for ADHD symptoms. Meta-regression analysis were used to investigate linear effects of dose (mg/kg/dose), and separate meta-analyses compared SMDs for 3 MPH dose ranges: low (0.10-0.30 mg/kg/dose), medium (0.31-0.60 mg/kg/dose), and high (0.61-1.00 mg/kg/dose).

Results

A total of 31 studies fulfilled inclusion criteria, comprising 804 children with ADHD. Methylphenidate had beneficial effects on all neurocognitive functions (d = 0.20-0.73). Significant linear dosing effects were found for ADHD symptoms and lower-order neurocognitive functions (baseline speed, variability in responding, nonexecutive memory), with greater enhancement of functioning with increasing dose. No dosing effects were found for higher-order neurocognitive functions (executive memory, inhibitory control, and cognitive flexibility). No detrimental effects of MPH were found on any of the investigated functions.

Conclusion

Methylphenidate was superior to placebo in improving ADHD symptoms and a broad range of neurocognitive functions; however, effects sizes regarding the effects of dose vary substantially between functions. Our data highlight the importance of considering both neurocognitive and symptomatic aspects of ADHD in clinical practice.

中文翻译：

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荟萃分析：哌醋甲酯对注意力缺陷/多动障碍儿童神经认知功能的剂量依赖性影响

客观的

神经认知缺陷是注意力缺陷/多动障碍 (ADHD) 解释模型的核心，并导致日常生活中的重大障碍。因此，确定哌醋甲酯 (MPH) 对广泛的神经认知功能的剂量影响并研究高剂量可能的损害影响非常重要。

方法

纳入安慰剂对照试验，调查 MPH 剂量对诊断为 ADHD 的儿童和青少年（5-18 岁）神经认知功能的影响。计算不同神经认知功能（基线速度、反应变异性、非执行记忆和执行记忆、抑制控制和认知灵活性）的效应量（标准化平均差 [S​​MDs]），如果可用，还计算 ADHD 症状。Meta 回归分析用于研究剂量的线性效应（mg/kg/dose），单独的 meta 分析比较了 3 MPH 剂量范围的 SMD：低（0.10-0.30 mg/kg/dose），中等（0.31-0.60 mg/kg/剂量）和高浓度（0.61-1.00 mg/kg/剂量）。

结果

共有 31 项研究符合纳入标准，包括 804 名患有多动症的儿童。哌醋甲酯对所有神经认知功能都有有益的影响（d = 0.20-0.73）。发现 ADHD 症状和低阶神经认知功能（基线速度、反应变异性、非执行记忆）具有显着的线性剂量效应，随着剂量的增加，功能增强更大。没有发现对高级神经认知功能（执行记忆、抑制控制和认知灵活性）的剂量影响。没有发现 MPH 对所研究的任何功能产生不利影响。

结论

哌醋甲酯在改善 ADHD 症状和广泛的神经认知功能方面优于安慰剂；然而，关于剂量效应的效应大小在函数之间存在很大差异。我们的数据强调了在临床实践中同时考虑 ADHD 的神经认知和症状方面的重要性。