A six-month, placebo-controlled trial of D-cycloserine co-administered with conventional antipsychotics in schizophrenia patients
A six-month, placebo-controlled trial of D-cycloserine co-administered with conventional antipsychotics in schizophrenia patients
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DOI：
10.1007/s00213-004-2032-2
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发表时间：
2005-04-01
影响因子：
3.4
通讯作者：
Schoenfeld, D
中科院分区：
文献类型：
--
作者：
Goff, DC;Herz, L;Schoenfeld, D
理由：d -环丝氨酸是n -甲基- d -天冬氨酸受体甘氨酸位点的部分激动剂，对精神分裂症的阴性症状和认知症状的疗效不一致。最有力的有效性证据来自于将d -环丝氨酸以50毫克/天的剂量添加到常规抗精神病药物中，持续时间为8周或更短的试验。目的：在为期6个月的临床试验中，评估常规抗精神病药物增加d -环丝氨酸对阴性症状和认知功能障碍的疗效。方法：采用双盲、平行组设计，将55例经常规抗精神病药物治疗、症状明显阴性的精神分裂症患者随机分为d -环丝氨酸50 mg/d组和安慰剂组，治疗6个月。结果：26名受试者完成了为期6个月的试验；治疗组之间的退出率没有差异。在8周或24周时，d -环丝氨酸治疗与安慰剂治疗在任何主要结局指标上都没有差异，包括阴性症状的反应和认知电池的表现。血清d -环丝氨酸浓度与阴性症状的反应无关。结论：d -环丝氨酸在本试验中没有表现出治疗效果，可能反映了高退出率，治疗血清浓度范围窄，所选结果测量的治疗效果适中，或随着时间的推移疗效丧失。由于d -环丝氨酸是一种部分激动剂，对甘氨酸位点的亲和力相对较低，因此潜在的治疗效果可能小于高亲和力的完全激动剂、甘氨酸和d -丝氨酸所达到的效果。
Rationale: D-Cycloserine, a partial agonist at the glycine site of the N-methyl-D-aspartate receptor, has demonstrated inconsistent efficacy for negative and cognitive symptoms of schizophrenia. The strongest evidence for efficacy has come from studies using D-cycloserine at a dose of 50 mg/day added to conventional antipsychotics in trials of 8 weeks duration or less. Objective: To assess the efficacy for negative symptoms and cognitive impairment of D-cycloserine augmentation of conventional antipsychotics in a 6-month trial. Methods: Fifty-five schizophrenia patients with prominent negative symptoms, treated with conventional antipsychotics, were randomly assigned to treatment with D-cycloserine 50 mg/day or placebo for 6 months in a double-blind, parallel group design. Results: Twenty-six subjects completed the 6-month trial; drop-out rates did not differ between treatment groups. D-Cycloserine treatment did not differ from placebo treatment on any primary outcome measure at 8 or 24 weeks, including response of negative symptoms and performance on a cognitive battery. Serum D-cycloserine concentrations did not correlate with response of negative symptoms. Conclusion: D-Cycloserine did not exhibit therapeutic effects in this trial, possibly reflecting the high drop-out rate, a narrow range of therapeutic serum concentrations, a modest magnitude of therapeutic effect for the selected outcome measures, or loss of efficacy over time. Because D-cycloserine is a partial agonist with relatively low affinity for the glycine site, the magnitude of potential therapeutic effect may be smaller than that achieved by the higher-affinity full agonists, glycine and D-serine.