Psychiatry Department, Hospital Universitari Vall dHebron, Barcelona, Spain.
CNS Drugs. 2011 Feb;25(2):157-69. doi: 10.2165/11539440-000000000-00000.
The efficacy of methylphenidate for adults with attention-deficit hyperactivity disorder (ADHD) shows wide between-study variability, which yields heterogeneous results in meta-analysis. The reasons for this variability have not been comprehensively investigated.
To determine the influence of treatment-related covariates of methylphenidate for adults with ADHD by means of meta-analysis. Clinical and methodological moderators and clinical trial reporting quality were also collected to control for their potential confounding effect.
We searched for randomized, placebo-controlled clinical trials investigating the efficacy of methylphenidate for adults with ADHD. The study outcome was the efficacy of methylphenidate for reducing ADHD symptom severity. Treatment-related covariates included dose, type of drug-release formulation (formulations with a continuous drug release vs those with a non-continuous drug release), dose regimen (fixed vs flexible) and treatment length. Clinical (presence of co-morbid substance use disorders [SUD]) and methodological (design and rater) covariates were also collected, in addition to clinical trial reporting quality. The standardized mean difference (SMD) was calculated for each study. The analysis of the influence of methylphenidate effect modifiers was performed by means of random-effects meta-regression.
Eighteen studies were included. Dose, type of formulation and SUD appeared to modify the efficacy of methylphenidate in the bivariate analysis. These variables were included in a multivariate meta-regression, which showed that methylphenidate, at an average dose of 57.4 mg/day, delivered by means of non-continuous-release formulations, had a moderate effect on ADHD symptoms compared with placebo (SMD 0.57-0.58). A dose-response relationship was found, indicating that efficacy could be increased by SMD 0.11-0.12 for every 10 mg increment of methylphenidate. Continuous-release formulations and co-morbid SUD appeared to reduce the efficacy of methylphenidate. Nevertheless, the effect of treatment formulation may have been confounded by co-morbid SUD, since all studies using this continuous-release formulation were conducted in dual ADHD-SUD patients. No residual heterogeneity was found.
This study shows that methylphenidate improves ADHD symptoms in adults in a dose-dependent fashion. The efficacy of methylphenidate appears to be reduced in patients with co-morbid SUD. It is unclear whether methylphenidate efficacy is influenced by the type of formulation, because the effect of this covariate is confounded by that of co-morbid SUD.
哌醋甲酯治疗成人注意缺陷多动障碍（ADHD）的疗效存在广泛的研究间变异性，导致荟萃分析结果存在异质性。其变异的原因尚未得到全面研究。
通过荟萃分析确定哌醋甲酯治疗成人 ADHD 的治疗相关协变量的影响。还收集了临床和方法学调节因素以及临床试验报告质量，以控制其潜在的混杂影响。
我们检索了评估哌醋甲酯治疗成人 ADHD 疗效的随机、安慰剂对照临床试验。研究结果为哌醋甲酯降低 ADHD 症状严重程度的疗效。治疗相关协变量包括剂量、药物释放剂型（具有持续药物释放的剂型与不具有持续药物释放的剂型）、剂量方案（固定剂量与灵活剂量）和治疗时间长度。还收集了临床（存在共病物质使用障碍[SUD]）和方法学（设计和评分者）协变量，以及临床试验报告质量。为每项研究计算了标准化均数差（SMD）。通过随机效应荟萃回归分析了哌醋甲酯效应修饰剂的影响。
纳入了 18 项研究。在双变量分析中，剂量、剂型和 SUD 似乎改变了哌醋甲酯的疗效。这些变量被纳入多元荟萃回归，结果表明，与安慰剂相比，哌醋甲酯（平均剂量 57.4mg/天）通过非持续释放剂型给药对 ADHD 症状具有中度疗效（SMD 0.57-0.58）。发现存在剂量反应关系，表明哌醋甲酯剂量每增加 10mg，疗效可增加 SMD 0.11-0.12。持续释放剂型和共病 SUD 似乎降低了哌醋甲酯的疗效。然而，由于所有使用这种持续释放剂型的研究都是在双 ADHD-SUD 患者中进行的，因此治疗剂型的效果可能受到共病 SUD 的混淆。未发现残余异质性。
本研究表明，哌醋甲酯以剂量依赖的方式改善成人 ADHD 症状。共病 SUD 的患者中哌醋甲酯的疗效降低。哌醋甲酯的疗效是否受剂型类型的影响尚不清楚，因为该协变量的效果受到共病 SUD 的影响。
