Once-weekly D-cycloserine effects on negative symptoms and cognition in schizophrenia: an exploratory study.
Once-weekly D-cycloserine effects on negative symptoms and cognition in schizophrenia: an exploratory study.
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DOI：
10.1016/j.schres.2008.08.012
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发表时间：
2008-12
影响因子：
4.5
通讯作者：
Green, Michael F.
中科院分区：
文献类型：
--
作者：
Goff, Donald C.;Cather, Corinne;Gottlieb, Jennifer D.;Evins, A. Eden;Walsh, Jared;Raeke, Lisa;Otto, Michael W.;Schoenfeld, David;Green, Michael F.
每日给药d -环丝氨酸对精神分裂症患者阴性症状的改善不一致，而在两项针对恐惧性焦虑患者的研究中，间歇性给药显著促进了基于暴露的治疗。在动物模型中，单次给药可增强记忆巩固，但重复给药会产生快速反应。本探索性研究的目的是评估每周一次d -环丝氨酸是否会对阴性症状和认知产生持续的改善。50名稳定的成年精神分裂症门诊患者接受除氯氮平以外的任何抗精神病药物治疗，其中38名随机双盲，在平行组中进行8周的附加试验，d-环丝氨酸50mg或安慰剂每周给药一次。在基线和给药前第8周进行症状评定量表和认知测试。作为记忆巩固的探索性分析，在基线和第一次每周剂量d -环丝氨酸后进行逻辑记忆测试，修改为测量7天后的回忆。主要结局指标是从基线到第8周SANS总分和综合认知评分的变化。33名受试者（87%）完成了试验。与安慰剂相比，d -环丝氨酸在第8周显著提高了SANS总分。8周时，d -环丝氨酸未改善认知能力。与安慰剂相比，第一剂量d -环丝氨酸显著改善了逻辑记忆测试中的延迟主题回忆。在逻辑记忆测试中，即时主题回忆和项目回忆的表现在不同处理之间没有差异。与安慰剂相比，每周服用一次d -环丝氨酸，持续8周，阴性症状持续改善，尽管有统计学意义，部分原因是安慰剂加重了阴性症状。与动物模型一致，单剂量d -环丝氨酸促进了7天后主题回忆测试中的记忆巩固。这些结果必须被认为是初步的，因为许多结果是在没有对多次试验进行校正的情况下检查的。这些发现表明，每周服用一次d -环丝氨酸治疗阴性症状值得进一步研究，d -环丝氨酸对记忆巩固的影响也值得进一步研究。
Daily dosing with D-cycloserine has inconsistently improved negative symptoms in schizophrenia patients, whereas intermittent dosing significantly facilitated exposure-based therapy in two studies of patients with phobic anxiety. In animal models, single dose administration enhances memory consolidation, but tachyphylaxis develops with repeated dosing. The objective of this exploratory study was to assess whether once-weekly dosing with D-cycloserine will produce persistent improvements in negative symptoms and cognition. Fifty stable adult schizophrenia outpatients treated with any antipsychotic except clozapine were enrolled and 38 were randomized, double-blind, in a parallel-group, 8-week add-on trial of D-cycloserine 50 mg or placebo administered once-weekly. Symptom rating scales and a cognitive battery were administered at baseline and week 8 before the dose of study drug. As an exploratory analysis of memory consolidation, the Logical Memory Test, modified to measure recall after 7 days, was administered at baseline and after the first weekly dose of D-cycloserine. The primary outcome measures were change from baseline to week 8 on the SANS total score and on a composite cognitive score. Thirty-three subjects (87%) completed the trial. D-cycloserine significantly improved SANS total scores compared to placebo at week 8. Cognitive performance did not improve with D-cycloserine at 8 weeks. Delayed thematic recall on the Logical Memory Test was significantly improved with the first dose of D-cycloserine compared to placebo. Performance on immediate thematic recall and item recall on the Logical Memory Test did not differ between treatments. Once-weekly dosing with D-cycloserine for 8 weeks produced persistent improvement of negative symptoms compared to placebo, although statistical significance was, in part, the result of worsening of negative symptoms with placebo. Consistent with animal models, a single dose of D-cycloserine facilitated memory consolidation tested after 7 days on a test of thematic recall. These results must be considered preliminary since a number of outcomes were examined without correction for multiple tests. These findings suggest that once-weekly dosing with D-cycloserine for the treatment of negative symptoms merits further study, as do D-cycloserine effects on memory consolidation.
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