Diazoxide in the treatment of schizophrenia: novel application of potassium channel openers in the treatment of schizophrenia
Diazoxide in the treatment of schizophrenia: novel application of potassium channel openers in the treatment of schizophrenia
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DOI：
10.1046/j.1365-2710.2002.00445.x
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发表时间：
2002-12-01
影响因子：
2
通讯作者：
Kamalipour, A
中科院分区：
文献类型：
--
作者：
Akhondzadeh, S;Mojtahedzadeh, V;Kamalipour, A
目的：精神分裂症是一种非常常见的疾病，影响世界人口的1%。患有精神分裂症的人会经历严重的痛苦，大约10%的人会自杀。精神分裂症的病因在很大程度上仍然是未知的。多巴胺拮抗剂治疗精神分裂症的某些症状相对无效，促使许多研究人员假设神经系统参与这种疾病的病理生理学。有人认为多巴胺偶联的三磷酸腺苷（ATP）敏感通道可能在代谢应激期间通过超极化细胞发挥作用，这一功能可能在精神分裂症患者中被破坏。因此，钾通道开放剂激活剂的应用可能对精神分裂症有益。二氮嗪是一种与噻嗪类利尿剂和钾通道开放剂相关的苯并噻二嗪衍生物。本调查的目的是评估二氮嗪的疗效，作为辅助剂在治疗schizophrenia.Methods：42例符合DSM IV慢性精神分裂症标准的患者完成了这项研究。患者随机接受氟哌啶醇20 mg/天+二氮嗪200 mg/天（21例受试者）或氟哌啶醇20 mg/天+安慰剂（21名受试者）在这项为期8周的双盲研究中。虽然两种方案在试验期间都显著降低了阳性、阴性和一般精神病理学症状的评分，氟哌啶醇和二氮嗪联合治疗在治疗阳性和一般精神病理学症状以及阳性和阴性症状量表（PANSS）总分方面显示出明显优于氟哌啶醇单药治疗。此外，在二氮嗪组中，在第2周观察到对阳性症状的快速起效，而在安慰剂组中，在第2周没有显著效果。两个协议之间的负scores.Conclusion：本研究的结果提出了一种新的应用钾通道开放剂/激活剂在神经精神疾病和二氮嗪可能是一种有效的辅助剂在精神分裂症的管理。
Objective: Schizophrenia is a very common disorder, affecting 1% of the world population. People who develop schizophrenia experience severe suffering and approximately 10% commit suicide. The causes of schizophrenia are still largely unknown. The relative ineffectiveness of dopamine antagonists to treat some symptoms of schizophrenia has promoted many investigators to postulate the involvement of the neuronal system in the pathophysiology of this disease. It has been suggested that the dopamine-coupled adenosine triphosphate (ATP)-sensitive channels may function by hyperpolarizing cells during metabolic stress, a function that may be disrupted in people with schizophrenia. Therefore, application of potassium channel openers activators may be beneficial in schizophrenia. Diazoxide is a benzothiadiazine derivative related to the thiazide diuretics and a potassium channel opener. The purpose of the present investigation was to assess the efficacy of diazoxide, as an adjuvant agent in the treatment of schizophrenia.Methods: Forty-two patients who met the DSM IV criteria for chronic schizophrenia completed the study. Patients were randomized to haloperidol 20 mg/day plus diazoxide 200 mg/day (21 subjects) or to haloperidol 20 mg/day plus placebo (21 subjects) in this 8-week double-blind study.Results: Although both protocols significantly decreased the score of the positive, negative and general psychopathological symptoms over the trial period, the combination of haloperidol and diazoxide showed a significant superiority over haloperidol alone in the treatment of positive and general psychopathology symptoms as well as positive and negative syndrome scale (PANSS) total scores. In addition, in the diazoxide group a rapid onset of action on the positive symptoms was observed in week 2, whereas in the placebo group there was no significant effect at week 2. No significant differences were observed between the two protocols on the negative scores.Conclusion: The results of this study present a novel application for potassium channel openers/activators in the neuropsychiatric disorders and diazoxide may be an effective adjuvant agent in the management of schizophrenia.