Clozapine is an atypical antipsychotic indicated in patients with treatment‐resistant schizophrenia which remains underused due to safety issues. Mechanisms behind these adverse effects are complex and not fully understood. They may involve immune‐related mechanisms, direct toxic effects and oxidative stress. Clozapine‐induced oxidative stress might indeed notably be involved in the onset of neutropenia, agranulocytosis, myocarditis, sialorrhea, and metabolic alterations. Therefore, the association of N‐acetylcysteine (NAC), an easily accessible, low‐cost and well tolerated antioxidant drug could be of interest in clozapine‐treated patients to improve clozapine safety. Furthermore, according to recent studies NAC could help to improve schizophrenia symptoms. We believe that the use of NAC in the context of clozapine prescribing merits further study, as it could improve clozapine safety which may lead to a wider use and ultimately improve the healthcare of thousands of patients. NAC could also secondarily show positive knock‐on effects for the patients by improving clinical symptoms of schizophrenia in synergy with clozapine, and by reducing substance abuse and thus by improving the patient's overall condition. However, given the rarity of clozapine‐induced severe adverse effects, only a large volume of data (e.g., National adverse events monitoring) could assess the benefits of NAC on clozapine safety.

中文翻译：

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N-乙酰半胱氨酸能否提高氯氮平的安全性？

氯氮平是一种非典型抗精神病药，适用于难治性精神分裂症患者，由于安全性问题，该药物仍未得到充分利用。这些不利影响背后的机制很复杂，尚未完全了解。它们可能涉及免疫相关机制、直接毒性作用和氧化应激。氯氮平诱导的氧化应激可能确实与中性粒细胞减少症、粒细胞缺乏症、心肌炎、流涎和代谢改变的发生有关。因此，N-乙酰半胱氨酸 (NAC) 是一种易于获得、低成本且耐受性良好的抗氧化药物，可能会引起氯氮平治疗患者的兴趣，以提高氯氮平的安全性。此外，根据最近的研究，NAC 可以帮助改善精神分裂症的症状。我们认为，在氯氮平处方中使用 NAC 值得进一步研究，因为它可以提高氯氮平的安全性，从而可能导致更广泛的使用并最终改善数千名患者的医疗保健。NAC 还可以通过与氯氮平协同改善精神分裂症的临床症状，减少药物滥用，从而改善患者的整体状况，从而对患者产生积极的连锁反应。然而，鉴于氯氮平引起的严重不良反应很少见，只有大量数据（例如，国家不良事件监测）才能评估 NAC 对氯氮平安全性的益处。NAC 还可以通过与氯氮平协同改善精神分裂症的临床症状，减少药物滥用，从而改善患者的整体状况，从而对患者产生积极的连锁反应。然而，鉴于氯氮平引起的严重不良反应很少见，只有大量数据（例如，国家不良事件监测）才能评估 NAC 对氯氮平安全性的益处。NAC 还可以通过与氯氮平协同改善精神分裂症的临床症状，减少药物滥用，从而改善患者的整体状况，从而对患者产生积极的连锁反应。然而，鉴于氯氮平引起的严重不良反应很少见，只有大量数据（例如，国家不良事件监测）才能评估 NAC 对氯氮平安全性的益处。