SUBANESTHETIC DOSES OF KETAMINE STIMULATE PSYCHOSIS IN SCHIZOPHRENIA
SUBANESTHETIC DOSES OF KETAMINE STIMULATE PSYCHOSIS IN SCHIZOPHRENIA
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DOI：
10.1016/0893-133x(94)00131-i
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发表时间：
1995-08-01
影响因子：
7.6
通讯作者：
TAMMINGA, CA
中科院分区：
文献类型：
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作者：
LAHTI, AC;KOFFEL, B;TAMMINGA, CA
我们采用双盲、安慰剂对照设计，以亚麻醉剂量（0.1、0.3和0.5 mg/kg）对精神分裂症患者给予氯胺酮，以评估n -甲基- d -天冬氨酸（NMDA）拮抗剂对精神分裂症患者精神状态的性质、剂量特征、时间过程和神经抑制剂调节作用。氯胺酮诱导氟哌啶醇治疗组的精神状态出现剂量相关的短期（< 30分钟）恶化，反映在0.3 mg/kg （p = 0.005）和0.5 mg/kg （p = 0.01）治疗组的BPRS总分显著升高。阳性症状（幻觉、妄想、思维障碍），而非阴性症状导致了这些变化。这些氯胺酮引起的精神病症状与受试者在疾病活跃发作时的症状惊人地相似。6名患者在停用抗精神病药4周后以相同设计重新测试的结果未能表明氟哌啶醇阻断氯胺酮诱导的精神病。一些受试者表现出延迟或延长（8-24小时）的拟精神作用，如伴有视觉幻觉的精神病恶化。这些数据表明，大脑中nmda敏感谷氨酸能传递的拮抗作用加剧了精神分裂症的症状。
We administered ketamine to schizophrenic individuals in a double-blind, placebo-controlled design using a range of subanesthetic doses (0.1, 0.3, and 0.5 mg/kg) to evaluate the nature, dose characteristics, time course, and neuroleptic modulation of N-methyl-D-aspartate (NMDA) antagonist action on mental status in schizophrenia. Ketamine induced a dose-related, short (< 30 minutes) worsening in mental status in the haloperidol-treated condition, reflected by a significant increase in BPRS total score for the 0.3 mg/kg (p = .005) and 0.5 mg/kg (p = .01) challenges. Positive symptoms (hallucinations, delusions, thought disorder), not negative symptoms accounted for these changes. These ketamine-induced psychotic symptoms were strikingly reminiscent of the subject's symptoms during active episodes of their illness. Results from six patients who were retested in the same design after being neuroleptic-free for 4 weeks failed to indicate that haloperidol blocks ketamine-induced psychosis. Several subjects evidenced delayed or prolonged (8-24 hours) psychotomimetic effects such as worsening of psychosis with visual hallucinations. These data suggest that antagonism of NMDA-sensitive glutamatergic transmission in brain exacerbates symptoms of schizophrenia.