Department of Psychiatry, China Medical University Hospital, Taichung, Taiwan2Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.
JAMA Psychiatry. 2013 Dec;70(12):1267-75. doi: 10.1001/jamapsychiatry.2013.2159.
In addition to dopaminergic hyperactivity, hypofunction of the N-methyl-d-aspartate receptor (NMDAR) has an important role in the pathophysiology of schizophrenia. Enhancing NMDAR-mediated neurotransmission is considered a novel treatment approach. To date, several trials on adjuvant NMDA-enhancing agents have revealed beneficial, but limited, efficacy for positive and negative symptoms and cognition. Another method to enhance NMDA function is to raise the levels of d-amino acids by blocking their metabolism. Sodium benzoate is a d-amino acid oxidase inhibitor.
To examine the clinical and cognitive efficacy and safety of add-on treatment of sodium benzoate for schizophrenia.
DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, placebo-controlled trial in 2 major medical centers in Taiwan composed of 52 patients with chronic schizophrenia who had been stabilized with antipsychotic medications for 3 months or longer.
Six weeks of add-on treatment of 1 g/d of sodium benzoate or placebo.
The primary outcome measure was the Positive and Negative Syndrome Scale (PANSS) total score. Clinical efficacy and adverse effects were assessed biweekly. Cognitive functions were measured before and after the add-on treatment.
Benzoate produced a 21% improvement in PANSS total score and large effect sizes (range, 1.16-1.69) in the PANSS total and subscales, Scales for the Assessment of Negative Symptoms-20 items, Global Assessment of Function, Quality of Life Scale and Clinical Global Impression and improvement in the neurocognition subtests as recommended by the National Institute of Mental Health's Measurement and Treatment Research to Improve Cognition in Schizophrenia initiative, including the domains of processing speed and visual learning. Benzoate was well tolerated without significant adverse effects.
Benzoate adjunctive therapy significantly improved a variety of symptom domains and neurocognition in patients with chronic schizophrenia. The preliminary results show promise for d-amino acid oxidase inhibition as a novel approach for new drug development for schizophrenia.
除了多巴胺能活性亢进外，N-甲基-D-天冬氨酸受体（NMDAR）功能低下在精神分裂症的病理生理学中也起着重要作用。增强 NMDAR 介导的神经传递被认为是一种新的治疗方法。迄今为止，几项关于辅助 NMDA 增强剂的试验表明，对于阳性和阴性症状以及认知，该方法具有有益但有限的疗效。另一种增强 NMDA 功能的方法是通过阻断其代谢来提高 D-氨基酸的水平。苯甲酸钠是一种 D-氨基酸氧化酶抑制剂。
研究苯甲酸钠辅助治疗精神分裂症的临床和认知疗效及安全性。
设计、地点和参与者：这是一项在台湾两家主要医疗中心进行的随机、双盲、安慰剂对照试验，共纳入 52 例慢性精神分裂症患者，这些患者在使用抗精神病药物稳定治疗 3 个月或更长时间后，接受苯甲酸钠或安慰剂的 6 周附加治疗。
苯甲酸钠或安慰剂 1g/d 的附加治疗。
主要结局测量指标为阳性和阴性综合征量表（PANSS）总分。每两周评估一次临床疗效和不良反应。附加治疗前后测量认知功能。
苯甲酸钠可使 PANSS 总分改善 21%，PANSS 总分和各分量表、20 项阴性症状评定量表、总体功能评定量表、生活质量量表和临床总体印象的效应量较大（范围为 1.16-1.69），并改善了神经认知子测试，这些测试是由美国国立精神卫生研究所的测量和治疗研究以改善精神分裂症认知倡议推荐的，包括加工速度和视觉学习等领域。苯甲酸钠耐受良好，无明显不良反应。
苯甲酸钠辅助治疗可显著改善慢性精神分裂症患者的多种症状领域和神经认知。初步结果表明，D-氨基酸氧化酶抑制可能成为开发治疗精神分裂症新药的新方法。
