D-serine efficacy as add-on pharmacotherapy to risperidone and olanzapine for treatment-refractory schizophrenia
D-serine efficacy as add-on pharmacotherapy to risperidone and olanzapine for treatment-refractory schizophrenia
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DOI：
10.1016/j.biopsych.2004.12.037
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发表时间：
2005-03-15
影响因子：
10.6
通讯作者：
Ermilov, M
中科院分区：
文献类型：
--
作者：
Heresco-Levy, U;Javitt, DC;Ermilov, M
背景：d -丝氨酸是n -甲基- d -天冬氨酸谷氨酸受体甘氨酸位点的选择性完全激动剂，目前可能是对抗精神分裂症中该受体类假设功能障碍的首选化合物。我们评估了d -丝氨酸辅助治疗用新型非典型抗精神病药物治疗的西方精神分裂症患者的有效性和安全性。方法：39名接受利培酮或奥氮平治疗的精神分裂症患者参加了一项双盲、安慰剂对照、为期6周的交叉试验，在抗精神病药物中添加30 mg/kg/天的d -丝氨酸。在整个研究过程中，每两周测量一次临床疗效和副作用。监测临床实验室参数和血清氨基酸水平。结果：d -丝氨酸给药诱导血清丝氨酸水平升高（p < 0.001），并导致阴性、阳性、认知和抑郁症状的显著改善（p < 0.001），以阳性和阴性综合征量表衡量。对于大约三分之一的样本，d -丝氨酸治疗导致简短精神病学评定量表总分显著降低（约20%）。d -丝氨酸耐受性良好，没有注意到临床实验室参数的有害变化。结论：1)提示d -丝氨酸辅助治疗可增强利培酮和奥氮平的疗效；2)证实d -丝氨酸对精神分裂症主要症状域的疗效；3)需要评估d -丝氨酸抗精神病药物单药治疗这种疾病。
Background: D-serine, a selective full agonist at the glycine site of N-methyl-D-aspartate glutamate receptor, might presently be the compound of choice for counteracting the hypothesized dysfunction of this receptor class in schizophrenia. Studies performed with Taiwanese patients indicate that D-serine significantly improves schizophrenia symptoms when used as adjuvant to conventional neuroleptics but not to clozapine. We assessed the efficacy and safety of D-serine adjuvant treatment for Occidental schizophrenia patients treated with newer atypical antipsychotics.Methods: Thirty-nine risperidone- or olanzapine-treated schizophrenia patients participated in a double-blind, placebo-controlled, 6-week crossover trial with 30 mg/kg/day D-serine added to their antipsychotic medication. Measures of clinical efficacy and side effects were determined biweekly throughout the study. Clinical laboratory parameters and amino acid serum levels were monitored.Results: D-serine administration induced increased serine serum levels (p < .001) and resulted in significant (p < .001) improvements in negative, positive, cognitive, and depression symptoms, as measured by the Positive and Negative Syndrome Scale. For approximately one third of the sample, D-serine treatment resulted in significant (> 20%) reductions in Brief Psychiatric Rating Scale total scores. D-serine was well tolerated, and no detrimental changes in clinical laboratory parameters were noted.Conclusions: These findings 1) indicate that risperidone and olanzapine efficacy might be augmented with D-serine adjuvant treatment; 2) confirm D-serine efficacy against main schizophrenia symptom domains; and 3) warrant the assessment of D-serine antipsycbotic monotherapy for this illness.