Akhondzadeh S, Mojtahedzadeh V, Mirsepassi G-R, Moin M, Amini-Nooshabadi H, Kamalipour A
Roozbeh Psychiatric Hospital, Tehran University of Medical sciences, Tehran, Iran.
J Clin Pharm Ther. 2002 Dec;27(6):453-9. doi: 10.1046/j.1365-2710.2002.00445.x.
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.
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.
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.
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.
精神分裂症是一种非常常见的疾病，影响着全球1%的人口。患精神分裂症的人遭受着巨大痛苦，约10%的患者会自杀。精神分裂症的病因在很大程度上仍然未知。多巴胺拮抗剂治疗精神分裂症某些症状的相对无效促使许多研究者推测神经系统参与了该疾病的病理生理学过程。有人提出，多巴胺偶联的三磷酸腺苷（ATP）敏感性通道可能在代谢应激期间通过使细胞超极化发挥作用，而这一功能在精神分裂症患者中可能受到破坏。因此，应用钾通道开放剂/激活剂可能对精神分裂症有益。二氮嗪是一种与噻嗪类利尿剂相关的苯并噻二嗪衍生物，也是一种钾通道开放剂。本研究的目的是评估二氮嗪作为辅助药物治疗精神分裂症的疗效。
42例符合DSM-IV慢性精神分裂症标准的患者完成了本研究。在这项为期8周的双盲研究中，患者被随机分为两组，一组接受每天20毫克氟哌啶醇加200毫克二氮嗪治疗（21名受试者），另一组接受每天20毫克氟哌啶醇加安慰剂治疗（21名受试者）。
尽管两种方案在试验期间均显著降低了阳性、阴性和一般精神病理症状的评分，但氟哌啶醇和二氮嗪联合用药在治疗阳性和一般精神病理症状以及阳性和阴性症状量表（PANSS）总分方面比单独使用氟哌啶醇显示出显著优势。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，而在安慰剂组中第2周没有显著效果。两组方案在阴性评分上没有观察到显著差异。
本研究结果为钾通道开放剂/激活剂在神经精神疾病中的应用提供了新的方向，二氮嗪可能是治疗精神分裂症的一种有效辅助药物。
