Carbon Maren, Kapoor Sandeep, Sheridan Eva, Al-Jadiri Aseel, Azzo Sally, Sarkaria Tania, Kane John M, Saito Ema, Correll Christoph U
The Zucker Hillside Hospital, Psychiatry, Glen Oaks, NY; Charité Berlin, Berlin.
The Zucker Hillside Hospital, Psychiatry, Glen Oaks, NY; Feinstein Institute for Medical Research, Manhasset, NY.
J Am Acad Child Adolesc Psychiatry. 2015 Sep;54(9):718-727.e3. doi: 10.1016/j.jaac.2015.06.015. Epub 2015 Jul 7.
Second-generation antipsychotic (SGA) effects in youth were monitored to quantify extrapyramidal side effects (EPS) and to identify risk profiles for treatment-emergent EPS.
Data were analyzed for the nonrandomized, prospective Second-generation Antipsychotic Treatment Indications, Effectiveness and Tolerability in Youth (SATIETY) inception cohort study. EPS were assessed at baseline and 4, 8, and 12 weeks after naturalistic SGA initiation for schizophrenia, mood, disruptive behavior, and autism spectrum disorders using the Simpson-Angus Scale (SAS), Barnes Akathisia Scale, Abnormal Involuntary Movement Scale (AIMS), and Treatment Emergent Side Effect Scale. Drug-induced parkinsonism was defined by incident mean SAS score >0.33, anticholinergic initiation, or increasing total SAS score ≥2 in patients with baseline EPS.
In 342 youth aged 13.6 ± 3.5 years (male = 58.2%, antipsychotic-naive = 65.8%), 15.2% developed drug-induced parkinsonism. Raw SGA-grouped drug-induced parkinsonism rates were as follows: quetiapine = 1.5%, olanzapine = 13.8%, risperidone = 16.1%, ziprasidone = 20.0%, and aripiprazole = 27.3%. SGA type, dose, higher age, and lower baseline functioning were jointly associated with drug-induced parkinsonism (R(2) = 0.18; p < .0001). Controlling for these factors, drug-induced parkinsonism rates were significantly lower only for quetiapine and olanzapine. Subjectively reported EPS (5%), EPS-related treatment discontinuation (3.3%), and anticholinergic initiation (3%) were infrequent. Anticholinergic initiation was most frequent with risperidone (10.2%; p = .0004). Treatment-emergent dyskinesia ranged from 4.5% (aripiprazole) to 15.5% (olanzapine). SGA type, younger age, white race/ethnicity, and baseline AIMS were jointly associated with treatment-emergent dyskinesia (R(2) = 0.31; p < .0001). Controlling for these factors, treatment-emergent dyskinesia rates differed among SGA subgroups, with higher rates with olanzapine and ziprasidone. At baseline, psychostimulant use was associated with dyskinesia, and number of psychotropic comedications was associated with subjective EPS.
In youth, SGA-related EPS rates did not generally exceed those reported in adults, with particularly low rates with quetiapine and olanzapine.
监测第二代抗精神病药物（SGA）对青少年的影响，以量化锥体外系副作用（EPS），并确定治疗中出现的EPS的风险特征。
对非随机、前瞻性的青少年第二代抗精神病药物治疗指征、有效性和耐受性（SATIETY）起始队列研究的数据进行分析。使用辛普森-安格斯量表（SAS）、巴恩斯静坐不能量表、异常不自主运动量表（AIMS）和治疗中出现的副作用量表，在自然状态下开始使用SGA治疗精神分裂症、心境障碍、破坏性行为障碍和自闭症谱系障碍的基线以及4、8和12周时评估EPS。药物性帕金森症的定义为：事件平均SAS评分>0.33、开始使用抗胆碱能药物，或基线有EPS的患者总SAS评分增加≥2。
在342名年龄为13.6±3.5岁的青少年中（男性占58.2%，初治抗精神病药物者占65.8%），15.2%出现了药物性帕金森症。按SGA分组的药物性帕金森症原始发生率如下：喹硫平=1.5%，奥氮平=13.8%，利培酮=16.1%，齐拉西酮=20.0%，阿立哌唑=27.3%。SGA类型、剂量、年龄较大和基线功能较低与药物性帕金森症共同相关（R²=0.18；p<.0001）。在控制这些因素后，仅喹硫平和奥氮平的药物性帕金森症发生率显著较低。主观报告的EPS（5%）、与EPS相关的治疗中断（3.3%）和抗胆碱能药物起始使用（3%）并不常见。抗胆碱能药物起始使用在利培酮治疗中最为常见（10.2%；p=.00）。治疗中出现的运动障碍发生率从4.5%（阿立哌唑）到15.5%（奥氮平）不等。SGA类型、年龄较小、白种人/种族和基线AIMS与治疗中出现运动障碍共同相关（R²=0.31；p<.0001）。在控制这些因素后，SGA亚组间治疗中出现运动障碍的发生率有所不同，奥氮平和齐拉西酮的发生率较高。在基线时，使用精神兴奋剂与运动障碍相关，精神科合并用药数量与主观EPS相关。
在青少年中，SGA相关的EPS发生率一般不超过成人报告的发生率，喹硫平和奥氮平的发生率尤其低。
