Goff D C, Tsai G, Levitt J, Amico E, Manoach D, Schoenfeld D A, Hayden D L, McCarley R, Coyle J T
Massachusetts General Hospital, Harvard Consolidated Department of Psychiatry, Boston, USA.
Arch Gen Psychiatry. 1999 Jan;56(1):21-7. doi: 10.1001/archpsyc.56.1.21.
In a preliminary dose-finding study, D-cycloserine, a partial agonist at the glycine modulatory site of the glutamatergic N-methyl-D-aspartate (NMDA) receptor, improved negative symptoms and cognitive function when added to conventional neuroleptics at a dose of 50 mg/d.
Forty-seven patients with schizophrenia meeting criteria for deficit syndrome were randomized to D-cycloserine, 50 mg/d (n=23) or placebo (n=24) added to their conventional neuroleptic for an 8-week, double-blind trial. Clinical assessments were performed at baseline and at weeks 1, 2, 4, 6, and 8. Serum concentrations of D-cycloserine, relevant amino acids, and homovanillic acid were assayed at baseline and at weeks 4 and 8. A cognitive battery was performed at baseline and at week 8.
Thirty-nine patients completed the 8-week trial. Seven dropouts occurred in the D-cycloserine group and 1 in the placebo group. The mean reduction in negative symptoms with D-cycloserine (23%) was significantly greater than with placebo (7%) as calculated by slopes representing Scale for the Assessment of Negative Symptoms (SANS) total scores. Improvement of negative symptoms was predicted by low neuroleptic dose and low baseline SANS total score. No differences were found in performance on any cognitive test between groups or in changes in any other clinical measure. Clinical response did not correlate significantly with serum amino acid concentrations at baseline or with concentrations of D-cycloserine at weeks 4 and 8.
These results support the hypothesis that agents acting at the glycine modulatory site of the NMDA receptor improve primary negative symptoms.
在一项初步剂量探索研究中，D - 环丝氨酸作为谷氨酸能N - 甲基 - D - 天冬氨酸（NMDA）受体甘氨酸调节位点的部分激动剂，当以50mg/d的剂量添加到传统抗精神病药物中时，可改善阴性症状和认知功能。
47名符合缺陷综合征标准的精神分裂症患者被随机分为两组，一组在其传统抗精神病药物基础上加用50mg/d的D - 环丝氨酸（n = 23），另一组加用安慰剂（n = 24），进行为期8周的双盲试验。在基线以及第1、2、4、6和8周进行临床评估。在基线以及第4和8周测定D - 环丝氨酸、相关氨基酸和高香草酸的血清浓度。在基线和第8周进行认知测试。
39名患者完成了8周试验。D - 环丝氨酸组有7名患者退出，安慰剂组有1名患者退出。根据阴性症状评估量表（SANS）总分计算，D - 环丝氨酸组阴性症状的平均减轻程度（23%）显著大于安慰剂组（7%）。低剂量抗精神病药物和低基线SANS总分可预测阴性症状的改善。两组在任何认知测试中的表现或任何其他临床指标的变化均未发现差异。临床反应与基线时的血清氨基酸浓度或第4和8周时的D - 环丝氨酸浓度均无显著相关性。
这些结果支持以下假设，即作用于NMDA受体甘氨酸调节位点的药物可改善原发性阴性症状。
