Department of Child and Adolescent Psychiatry, Université Pierre et Marie Curie, GH Pitié-Salpétrière, Paris, France.
J Clin Psychopharmacol. 2012 Jun;32(3):309-16. doi: 10.1097/JCP.0b013e3182549259.
In adults, second-generation antipsychotics (SGAs) have a low frequency of extrapyramidal syndrome (EPS) and a moderate frequency of metabolic adverse effects. Here we aimed to assess short-term adverse effects of SGAs in children and adolescents. We searched for relevant studies in MEDLINE and EMBASE (1996-2010), Food and Drug Administration and European Medicines Agency clinical trial registries, and reference lists of review articles. We found 41 were short-term (3-12 weeks) controlled studies that evaluated SGA adverse effects in youths. Using Bayesian meta-analysis, we analyzed odds ratios (ORs) or mean average effects. Numbers of arms (subjects) in the 41 trials were aripiprazole, 10 (n = 671); olanzapine, 14 (n = 413); quetiapine, 10 (n = 446); risperidone, 25 (n = 1040); ziprasidone, 4 (n = 228); clozapine, 5 (n = 79); and placebo/untreated, 23 (n = 1138), totaling 93 arms (4015 patients). Clozapine was assessed only for weight gain and somnolence. Compared with placebo, significant treatment-related increases were observed for weight gain with olanzapine (mean ± SD = 3.99 ± 0.42 kg; 95% credible interval, 3.17-4.84 kg), clozapine (2.38 ± 1.13 kg; 95% credible interval, 0.19-4.62 kg), risperidone (2.02 ± 0.32 kg; 95% credible interval, 1.39-2.66 kg), quetiapine (1.74 ± 0.38 kg; 95% credible interval, 0.99-2.5 kg), and aripiprazole (0.89 ± 0.32 kg; 95% credible interval, 0.26-1.51 kg); glucose levels with risperidone (3.7 ± 1.36 mg/dL; 95% credible interval, 1.08-6.42 mg/dL) and olanzapine (2.09 ± 1.08 mg/dL; 95% credible interval, 0.13-4.32 mg/dL); cholesterol levels with quetiapine (10.77 ± 2.14 mg/dL; 95% credible interval, 6.6-14.95 mg/dL) and olanzapine (4.46 ± 1.65 mg/dL; 95% credible interval, 1.24-7.73 mg/dL); triglyceride levels with olanzapine (20.18 ± 5.26 mg/dL; 95% credible interval, 9.85-30.53 mg/dL) and quetiapine (19.5 ± 3.92 mg/dL; 95% credible interval, 11.84-27.17 mg/dL); hyperprolactinemia with risperidone (OR, 38.63; 95% credible interval, 8.62-125.6), olanzapine (OR, 15.6; 95% credible interval, 4.39-41.1), and ziprasidone (OR, 9.35; 95% credible interval, 1.24-37.03); and EPS with ziprasidone (OR, 20.56; 95% credible interval, 3.53-68.94), olanzapine (OR, 6.36; 95% credible interval, 2.43-13.84), aripiprazole (OR, 3.79; 95% credible interval, 2.17-6.17), and risperidone (OR, 3.71; 95% credible interval, 2.18-6.02). All SGAs increased the risk of somnolence/sedation. We conclude that short-term metabolic effects and EPS are frequent in children treated with SGAs. Second-generation antipsychotics have distinct profiles of secondary effects, which should be considered in making treatment decisions.
在成年人中，第二代抗精神病药物（SGAs）的锥体外系综合征（EPS）发生率低，代谢不良作用发生率中等。在此，我们旨在评估儿童和青少年使用 SGA 的短期不良作用。我们在 MEDLINE 和 EMBASE（1996-2010 年）、食品和药物管理局和欧洲药品管理局临床试验登记处以及综述文章的参考文献列表中搜索了相关研究。我们找到了 41 项短期（3-12 周）对照研究，评估了青少年使用 SGA 的不良作用。我们使用贝叶斯荟萃分析分析了优势比（ORs）或平均平均效应。41 项试验的臂数（受试者）分别为阿立哌唑 10（n=671）、奥氮平 14（n=413）、喹硫平 10（n=446）、利培酮 25（n=1040）、齐拉西酮 4（n=228）、氯氮平 5（n=79）和安慰剂/未治疗 23（n=1138），共 93 个臂（4015 名患者）。氯氮平仅评估体重增加和嗜睡。与安慰剂相比，奥氮平（体重增加的平均标准差=3.99±0.42kg；95%可信区间，3.17-4.84kg）、氯氮平（2.38±1.13kg；95%可信区间，0.19-4.62kg）、利培酮（2.02±0.32kg；95%可信区间，1.39-2.66kg）、喹硫平（1.74±0.38kg；95%可信区间，0.99-2.5kg）和阿立哌唑（0.89±0.32kg；95%可信区间，0.26-1.51kg）体重增加显著相关；利培酮（3.7±1.36mg/dL；95%可信区间，1.08-6.42mg/dL）和奥氮平（2.09±1.08mg/dL；95%可信区间，0.13-4.32mg/dL）血糖水平升高；喹硫平（10.77±2.14mg/dL；95%可信区间，6.6-14.95mg/dL）和奥氮平（4.46±1.65mg/dL；95%可信区间，1.24-7.73mg/dL）胆固醇水平升高；奥氮平（20.18±5.26mg/dL；95%可信区间，9.85-30.53mg/dL）和喹硫平（19.5±3.92mg/dL；95%可信区间，11.84-27.17mg/dL）甘油三酯水平升高；利培酮（OR，38.63；95%可信区间，8.62-125.6）、奥氮平（OR，15.6；95%可信区间，4.39-41.1）和齐拉西酮（OR，9.35；95%可信区间，1.24-37.03）催乳素升高；齐拉西酮（OR，20.56；95%可信区间，3.53-68.94）、奥氮平（OR，6.36；95%可信区间，2.43-13.84）、阿立哌唑（OR，3.79；95%可信区间，2.17-6.17）和利培酮（OR，3.71；95%可信区间，2.18-6.02）锥体外系综合征风险增加。所有 SGA 都增加了嗜睡/镇静的风险。我们的结论是，儿童短期使用代谢不良作用和 EPS 是常见的。第二代抗精神病药物具有不同的次要作用特征，在做出治疗决策时应加以考虑。
