摘要
氯氮平已被视为难治性精神分裂症患者的最后一线抗精神病药。但是，许多患者对氯氮平仍然没有反应，这被称为“氯氮平耐药”，“抗过度治疗”，或处于无法治愈的状态。到目前为止，尚无令人信服的证据表明氯氮平可增强疗效。在临床试验中，包括多种N-甲基-Daspartate（NMDA）受体（NMDAR）增强剂（例如甘氨酸，D-丝氨酸，D-环丝氨酸和N甲基甘氨酸（肌氨酸））的新型治疗方法均告失败。 早些时候，据报道抑制D-氨基酸氧化酶（DAAO）可能会代谢D-氨基酸并激活NMDAR，这对除氯氮平以外接受抗精神病药治疗的精神分裂症患者有益。最近一项随机，双盲，安慰剂对照的临床试验发现，DAAO抑制剂苯甲酸钠的添加可改善对氯氮平耐药的精神分裂症患者的临床症状，可能是通过抑制DAAO（并由此激活NMDAR）和抗氧化作用。好;此外，苯甲酸钠没有明显的副作用，表明该疗法以每天2 g的剂量连续6周是安全的。有必要进行更多的研究来阐明苯甲酸钠治疗精神分裂症的机制以及这种严重脑病的病因。如果可以再次证实这一发现，这种方法可能为治疗最难治性精神分裂症带来新的希望。 这篇综述总结了治疗性耐药，尤其是氯氮平耐药性精神分裂症的临床试验和相关机制的现状。还强调了理解分子回路开关的重要性，这可以恢复精神分裂症患者的脑功能。还讨论了为最难治愈的精神分裂症开发更好的治疗方法的未来方向.
关键词: 精神分裂症，氯氮平，耐氯氮平的精神分裂症，NMDAR，DAAO，DAAO抑制剂，苯甲酸钠，抗氧化剂。
图形摘要
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