Efficacy, safety and variability in pharmacotherapy for adults with attention deficit hyperactivity disorder: a meta-analysis and meta-regression in over 9000 patients
Efficacy, safety and variability in pharmacotherapy for adults with attention deficit hyperactivity disorder: a meta-analysis and meta-regression in over 9000 patients
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DOI：
10.1007/s00213-015-4099-3
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发表时间：
2016-01-01
影响因子：
3.4
通讯作者：
Capella, D.
中科院分区：
文献类型：
--
作者：
Cunill, R.;Castells, X.;Capella, D.
对成人注意缺陷多动障碍（ADHD）药物干预的随机、安慰剂对照临床试验（RPCCT）结果的变异性进行系统评价和荟萃分析。研究结果是全因治疗中止，对ADHD症状的疗效和安全性。收集患者、干预和研究设计相关协变量。采用Meta回归分析方法，共纳入44篇文献，涉及9952例患者。药物治疗组的全因治疗中止率略高于安慰剂组（比值比（OR）= 1.18; 95%置信区间（CI）1.02，1.36; p = 0.003）。在提供伴随心理治疗的研究中，观察到全因治疗中止的结局优于未提供的研究（OR率（ROR）= 0.68，p = 0.048）。药物治疗对减少ADHD症状有效（标准化平均差（SMD）= 0.45; 95% CI 0.37，0.52; p < 0.00001），在调查兴奋剂药物的研究中发现了更强的干预作用（SMD差异（Diff SMD）= 0.18，p = 0.017），在较短的研究中（Diff SMD =-0.01，p = 0.044），以及当使用临床医生评定量表时（Diff SMD = 0.44，p < 0.0001）。药物治疗与更频繁的不良事件（AE）相关（OR = 2.29; 95% CI 1.97，2.66; p = 0.006）。具有导入期和既往接受兴奋剂治疗的患者比例较高的研究与更好的安全性结局相关（ROR = 0.59，p = 0.017; ROR = 0.98，p = 0.036）。药物治疗提供了轻度症状改善，但与安慰剂相比，与频繁的AE和更高的治疗中止相关，特别是当没有给予伴随的心理治疗时。兴奋剂似乎比非兴奋剂药物更有效，前者应优于后者。药物治疗的有效性应随时间进行监测，因为它可能会逐渐降低。
The factors underlying the variability in the results of randomized, placebo-controlled clinical trials (RPCCT) assessing pharmacological interventions for adults with attention deficit hyperactivity disorder (ADHD) are not fully understood.A systematic review and meta-analysis of RPCCT comparing pharmacological treatment and placebo in adults with ADHD was carried out. The study outcomes were all-cause treatment discontinuation, efficacy on ADHD symptoms, and safety. Patient-, intervention-, and study design-related covariates were collected. Meta-regression methods were applied.Forty-four studies involving 9952 patients were included. All-cause treatment discontinuation was slightly higher with pharmacological treatment than with placebo (odds ratio (OR) = 1.18; 95 % confidence interval (CI) 1.02, 1.36; p = 0.003). A better outcome on all-cause treatment discontinuation was observed in studies that provided concomitant psychotherapy when compared to those that did not (rate of OR (ROR) = 0.68, p = 0.048). Pharmacological treatment was efficacious for reducing ADHD symptoms (standardized mean difference (SMD) = 0.45; 95 % CI 0.37, 0.52; p < 0.00001), with stronger intervention effects found in studies investigating stimulant drugs (difference of SMD (Diff SMD) = 0.18, p = 0.017), in shorter studies (Diff SMD = -0.01, p = 0.044), and when clinician-rated scales were used (Diff SMD = 0.44, p < 0.0001). Pharmacological treatment was associated with more frequent adverse events (AEs) (OR = 2.29; 95 % CI 1.97, 2.66; p = 0.006). Studies with a lead-in phase and with a higher proportion of patients previously treated with stimulants were associated with a better safety outcome (ROR = 0.59, p = 0.017; ROR = 0.98, p = 0.036, respectively).Pharmacological treatment provides mild symptom improvement but is associated with frequent AEs and higher treatment discontinuation than placebo, particularly when no concomitant psychotherapy is administered. Stimulants appear more efficacious than non-stimulant drugs and the former should be preferred over the latter. The efficacy of pharmacological treatment should be monitored over time because it may decrease progressively.