Whyte John, Myers Robin
Moss Rehabilitation Research Institute, 2nd Floor, West Building, 60 E. Township Line Road, Elkins Park, PA 19027, USA.
Am J Phys Med Rehabil. 2009 May;88(5):410-8. doi: 10.1097/PHM.0b013e3181a0e3a0.
The common hypnotic, zolpidem, has been reported to temporarily restore consciousness to individuals in the chronic vegetative state. In drug responders, repeated dosing appears to maintain consciousness. The frequency of such responses, however, is unknown and is important both to guide clinical use and to plan further research on the mechanisms underlying drug response. The objectives of this study were to obtain an estimate of the frequency of clinically significant responses among individuals with disorders of consciousness, to determine whether less obvious drug responses are present among "nonresponders," and to identify clinical features characteristic of zolpidem responders.
Participants were individuals in the vegetative or minimally conscious state at least 1 month after brain injury. Each participant was studied individually in a double-blind, placebo-controlled, crossover design, once on zolpidem (10 mg per feeding tube) and once on placebo. Each assessment involved baseline administration of the Coma Recovery Scale-Revised, followed immediately by administration of the study drug, followed by 5 hourly readministrations of the Coma Recovery Scale-Revised. A replication pair of assessments was available for drug responders.
: One of 15 participants (6.7%) demonstrated a clinically significant response, which altered his assessment from the vegetative state to the minimally conscious state, and this result was repeated in the replication assessment. The remaining 14 participants showed no evidence of a subclinical response to the drug.
These results confirm that clinically significant responses to zolpidem among individuals with disorders of consciousness do occur in a minority of patients and can be replicated. Failure to find a trend toward improved performance on zolpidem among nonresponders suggests a bimodal rather than a graded response to the drug. The fact that only one drug responder was identified in this small study prevents assessment of features characteristic of drug responders.
据报道，常见的催眠药唑吡坦可使慢性植物状态的个体暂时恢复意识。在药物反应者中，重复给药似乎能维持意识。然而，这种反应的频率尚不清楚，这对于指导临床应用以及规划关于药物反应潜在机制的进一步研究都很重要。本研究的目的是估计意识障碍个体中具有临床意义的反应频率，确定“无反应者”中是否存在不太明显的药物反应，并识别唑吡坦反应者的临床特征。
参与者为脑损伤后至少1个月处于植物状态或最低意识状态的个体。每位参与者均采用双盲、安慰剂对照、交叉设计进行单独研究，一次服用唑吡坦（每根饲管10毫克），一次服用安慰剂。每次评估包括首先进行昏迷恢复量表修订版的基线评估，随后立即给予研究药物，然后每小时重复进行5次昏迷恢复量表修订版的评估。药物反应者可进行一组重复评估。
15名参与者中有1名（6.7%）表现出具有临床意义的反应，其评估从植物状态转变为最低意识状态，且该结果在重复评估中得到重现。其余14名参与者未显示出对该药物有亚临床反应的证据。
这些结果证实，意识障碍个体中对唑吡坦具有临床意义的反应确实在少数患者中出现且可重现。在无反应者中未发现使用唑吡坦后表现改善的趋势，这表明对该药物的反应是双峰的而非分级的。在这项小型研究中仅识别出1名药物反应者，这使得无法评估药物反应者的特征。
