Star Kristina, Iessa Noha, Almandil Noor B, Wilton Lynda, Curran Sarah, Edwards I Ralph, Wong Ian C K
Uppsala Monitoring Centre, WHO Collaborating Centre for International Drug Monitoring, Uppsala, Sweden.
J Child Adolesc Psychopharmacol. 2012 Dec;22(6):440-51. doi: 10.1089/cap.2011.0134.
Rhabdomyolysis is a rare and potentially serious adverse drug reaction (ADR) to antipsychotic medicines. The aim of this study was to investigate the clinical circumstances surrounding the diagnosis of rhabdomyolysis in children and adolescents treated with antipsychotic medicines. We also critically reviewed individual case safety reports (ICSRs) of suspected ADRs to evaluate how clinically useful they can be in a case series analysis.
This was a descriptive and an exploratory study. Published case reports and ICSRs from the World Health Organization (WHO) Global ICSR database, VigiBase, reported with rhabdomyolysis and antipsychotic medicines for patients ≤17 years years of age were described. Reporting patterns of ICSRs with rhabdomyolysis and antipsychotic medicines were explored in VigiBase for children and adolescents and for adults. The VigiBase ICSRs were also systematically evaluated regarding the report content.
Of the 26 evaluated reports, 6 co-reported neuroleptic malignant syndrome (NMS) and 20 reports concerned rhabdomyolysis in the absence of NMS. The reported suspected antipsychotic medicines for these 20 reports were olanzapine, risperidone, haloperidol, paliperidone, quetiapine, clozapine, cyamemazine, and aripiprazole. In VigiBase, rhabdomyolysis (in the absence of NMS) was reported more frequently with olanzapine relative to all reports for children and adolescents with antipsychotic medicines. In the range of events that preceded rhabdomyolysis, muscle pains and abdominal pain were commonly recorded to have started during the week prior to the diagnosis. Other preceding symptoms were general weakness and dark urine. Onset of rhabdomyolysis for most patients occurred at any time within 2 months of starting antipsychotic treatment, in several cases triggered by changes to the patient's drug therapy or known risk factors of rhabdomyolysis. It was found that ICSRs can contribute with additional information, but that access to free text and narratives were crucial in order to capture clinically useful features of rhabdomyolysis.
Monitoring of children and adolescents needs to be intensified during dose increases, or when a new, added, or switched antipsychotic medicine is introduced to their drug regimen, and during exposure to known risk factors for rhabdomyolysis. The development of seemingly nonserious events, such as abdominal pain, muscle pain, weakness, and dark urine, should be followed up during antipsychotic use, as they might be precursory events to rhabdomyolysis that eventually could develop into acute renal failure.
横纹肌溶解症是抗精神病药物罕见且可能严重的药物不良反应（ADR）。本研究旨在调查接受抗精神病药物治疗的儿童和青少年发生横纹肌溶解症诊断时的临床情况。我们还严格审查了疑似ADR的个体病例安全报告（ICSR），以评估其在病例系列分析中的临床实用性。
这是一项描述性和探索性研究。描述了世界卫生组织（WHO）全球ICSR数据库VigiBase中已发表的病例报告以及17岁及以下患者横纹肌溶解症和抗精神病药物相关的ICSR。在VigiBase中探索了儿童、青少年和成人群体中横纹肌溶解症和抗精神病药物相关ICSR的报告模式。还对VigiBase中的ICSR报告内容进行了系统评估。
在26份评估报告中，6份共同报告了抗精神病药物恶性综合征（NMS），20份报告涉及无NMS情况下的横纹肌溶解症。这20份报告中所涉及的疑似抗精神病药物为奥氮平、利培酮、氟哌啶醇、帕利哌酮、喹硫平、氯氮平、氰美马嗪和阿立哌唑。在VigiBase中，相对于所有抗精神病药物治疗的儿童和青少年报告，奥氮平导致横纹肌溶解症（无NMS）的报告更为频繁。在横纹肌溶解症发生之前的一系列事件中，肌肉疼痛和腹痛通常记录为在诊断前一周开始出现。其他前驱症状为全身无力和深色尿液。大多数患者横纹肌溶解症的发作发生在开始抗精神病药物治疗后的2个月内的任何时间，在某些情况下是由患者药物治疗的改变或已知的横纹肌溶解症风险因素引发的。发现ICSR可以提供额外信息，但获取自由文本和叙述对于捕捉横纹肌溶解症的临床有用特征至关重要。
在增加剂量期间，或当向儿童和青少年的药物治疗方案中引入新的、添加的或更换的抗精神病药物时，以及在接触已知的横纹肌溶解症风险因素期间，需要加强对他们的监测。在使用抗精神病药物期间，应跟踪看似不严重的事件的发展，如腹痛、肌肉疼痛、无力和深色尿液，因为它们可能是横纹肌溶解症的前驱事件，最终可能发展为急性肾衰竭。
