Biagetti Rebecca, Caiazza Laura, Giuva Tiziana, Pirani Graziella, Di Biase Anna Rita, Bergonzini Patrizia, Caramaschi Elisa, Spezia Elisabetta, Iughetti Lorenzo, Lupetti Ilaria, Donati Cristina, Persico Antonio M
Residency Program in Child & Adolescent Neuropsychiatry, University of Modena and Reggio Emilia, Modena, Italy.
Child & Adolescent Neuropsychiatry Service, Department of Mental Health and Dependence, AUSL of Modena, Modena, Italy.
Psychiatry Res. 2025 Sep;351:116646. doi: 10.1016/j.psychres.2025.116646. Epub 2025 Jul 18.
Treatment-resistant schizophrenia and bipolar disorder represent first-line indications for clozapine prescription in children and adolescents, who display treatment-resistance significantly more often than adults. However, titrating clozapine up to reach an effective dose may become impossible if serious adverse events occur, forcing drug discontinuation. Here we systematically review all articles available in PubMed regarding clozapine-associated cardiac toxicity in children and adolescents, primarily including myocarditis and pericarditis, and focus on the feasibility of clozapine rechallenge after drug discontinuation. Our systematic review identifies 12 articles reporting 13 pediatric cases of clozapine-associated cardiac toxicity. Seven patients discontinued the drug and no rechallenge was attempted. Five underwent clozapine rechallenge: 4 (80.0 %) were successfully titrated up to an effective clozapine dose without recurrence of cardiac toxicity, whereas 1 (20.0 %) displayed signs of myocarditis soon after restarting clozapine; in one case, clozapine was not stopped and the initial signs of cardiac inflammation quickly abated. We also report a new pediatric case of successful clozapine rechallenge following one episode of myocarditis and a subsequent pericarditis occurred during the titration phase. Clozapine treatment was successfully continued at a reduced, yet effective dose. Overall, the available evidence, though limited, supports clozapine rechallenge after drug discontinuation due to cardiac toxicity in children and adolescents. Ensuring full cardiac recovery before rechallenging with clozapine, starting with a low dose (6.5-12.5 mg/d), a slow titration rate (12.5-25 mg/d per week), avoiding the co-administration of valproic acid (Depakene), and frequent monitoring of cardiac and inflammatory parameters appear critical to the success of clozapine rechallenge.
难治性精神分裂症和双相情感障碍是儿童和青少年使用氯氮平处方的一线适应症，他们比成年人更常出现治疗抵抗。然而，如果发生严重不良事件，可能无法将氯氮平滴定至有效剂量，从而迫使停药。在此，我们系统回顾了PubMed中所有关于儿童和青少年氯氮平相关心脏毒性的文章，主要包括心肌炎和心包炎，并关注停药后重新使用氯氮平的可行性。我们的系统回顾确定了12篇报告13例儿童氯氮平相关心脏毒性病例的文章。7例患者停药，未尝试重新用药。5例进行了氯氮平重新用药：4例（80.0%）成功滴定至氯氮平有效剂量，心脏毒性未复发，而1例（20.0%）在重新开始使用氯氮平后不久出现心肌炎症状；在1例中，未停用氯氮平，心脏炎症的初始症状迅速缓解。我们还报告了1例新的儿科病例，在滴定阶段发生1次心肌炎和随后的心包炎后成功重新使用氯氮平。氯氮平治疗以降低但有效的剂量成功继续。总体而言，现有证据虽然有限，但支持儿童和青少年因心脏毒性停药后重新使用氯氮平。在重新使用氯氮平之前确保心脏完全恢复，从低剂量（6.5 - 12.5毫克/天）开始，缓慢滴定速率（每周12.5 - 25毫克/天），避免同时使用丙戊酸（德巴金），以及频繁监测心脏和炎症参数，对于氯氮平重新用药的成功似乎至关重要。
