BACKGROUND Clozapine is the last-line antipsychotic agent for refractory schizophrenia. To date, there is no convincing evidence for augmentation on clozapine. Activation of N-methyl-D-aspartate receptors, including inhibition of D-amino acid oxidase that may metabolize D-amino acids, has been reported to be beneficial for patients receiving antipsychotics other than clozapine. This study aimed to examine the efficacy and safety of a D-amino acid oxidase inhibitor, sodium benzoate, for schizophrenia patients who had poor response to clozapine. METHODS We conducted a randomized, double-blind, placebo-controlled trial. Sixty schizophrenia inpatients that had been stabilized with clozapine were allocated into three groups for 6 weeks' add-on treatment of 1 g/day sodium benzoate, 2 g/day sodium benzoate, or placebo. The primary outcome measures were Positive and Negative Syndrome Scale (PANSS) total score, Scale for the Assessment of Negative Symptoms, Quality of Life Scale, and Global Assessment of Functioning. Side effects and cognitive functions were also measured. RESULTS Both doses of sodium benzoate produced better improvement than placebo in the Scale for the Assessment of Negative Symptoms. The 2 g/day sodium benzoate also produced better improvement than placebo in PANSS-total score, PANSS-positive score, and Quality of Life Scale. Sodium benzoate was well tolerated without evident side effects. The changes of catalase, an antioxidant, were different among the three groups and correlated with the improvement of PANSS-total score and PANSS-positive score in the sodium benzoate group. CONCLUSIONS Sodium benzoate adjuvant therapy improved symptomatology of patients with clozapine-resistant schizophrenia. Further studies are warranted to elucidate the optimal dose and treatment duration as well as the mechanisms of sodium benzoate for clozapine-resistant schizophrenia.

中文翻译：

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苯甲酸钠，一种 D-氨基酸氧化酶抑制剂，加入氯氮平治疗精神分裂症：一项随机、双盲、安慰剂对照试验

背景氯氮平是治疗难治性精神分裂症的最后一线抗精神病药。迄今为止，没有令人信服的证据表明氯氮平的剂量增加。据报道，N-甲基-D-天冬氨酸受体的激活，包括抑制可能代谢 D-氨基酸的 D-氨基酸氧化酶，对接受除氯氮平以外的抗精神病药物的患者有益。本研究旨在检查 D-氨基酸氧化酶抑制剂苯甲酸钠对氯氮平反应不佳的精神分裂症患者的疗效和安全性。方法 我们进行了一项随机、双盲、安慰剂对照试验。60 名已用氯氮平稳定的精神分裂症住院患者被分为三组，分别接受 1 克/天苯甲酸钠、2 克/天苯甲酸钠或安慰剂的 6 周附加治疗。主要结局指标是阳性和阴性综合征量表 (PANSS) 总分、阴性症状评估量表、生活质量量表和总体功能评估。还测量了副作用和认知功能。结果 在阴性症状评估量表中，两种剂量的苯甲酸钠都比安慰剂产生了更好的改善。在 PANSS 总分、PANSS 阳性评分和生活质量量表方面，2 克/天的苯甲酸钠也比安慰剂产生了更好的改善。苯甲酸钠耐受性良好，无明显副作用。过氧化氢酶（一种抗氧化剂）的变化在三组之间不同，并且与苯甲酸钠组中 PANSS 总分和 PANSS 阳性评分的改善相关。结论苯甲酸钠辅助治疗改善了氯氮平耐药性精神分裂症患者的症状。需要进一步的研究来阐明苯甲酸钠对氯氮平耐药的精神分裂症的最佳剂量和治疗持续时间以及机制。