Adjunctive Minocycline in Clozapine Treated Patients for Psychosis and Cognition

描述（由申请人提供）：超过60%的氯氮平治疗患者继续出现持续性症状和认知障碍，几乎没有数据支持循证建议，以指导临床医生治疗这些患者。最近的数据表明，米诺环素的辅助治疗可能会改善服用氯氮平的精神分裂症患者的症状。米诺环素具有新颖和有趣的分子效应，包括AMPA受体调节和抗炎及神经保护作用，这表明它可能在神经和精神疾病的治疗中具有重要作用。米诺环素目前是通用的;它的副作用是很好的描述和最小的。拟议的10周双盲随机治疗研究旨在证明，二甲胺四环素为持续阳性症状、认知障碍和/或精神分裂症病理学的其他组成部分的患者提供上级疗效。这些知识可能会导致更有效地治疗精神分裂症患者。这项新的研究本身可能会导致更好地了解阳性症状和认知障碍的病理生理学，这可能有助于改善未来的治疗方法。此外，我们将研究米诺环素对炎症细胞因子的影响，以及这些细胞因子在症状改善中的介导作用。 公共卫生相关性：很少有证据可用于指导治疗精神分裂症患者，尽管氯氮平治疗症状持续存在。初步数据表明，米诺环素可能是有效的氯氮平治疗的患者，可能通过其谷氨酸（AMPA）系统的调制和炎症细胞因子的影响。本研究在一项双盲随机试验中，对服用氯氮平后症状持续的精神分裂症患者进行了二甲胺四环素与安慰剂的对比研究。我们将检查神经病学，神经认知功能，炎症细胞因子和患者满意度/幸福感的变化。

DESCRIPTION (provided by applicant): Over 60% of people treated with clozapine continue to have persistent symptoms and cognitive impairments and little data is available to support evidence-based recommendations to guide clinicians in treating these patients. Recent data suggests that adjunct treatment with minocycline may offer symptom improvement in patients with schizophrenia who are taking clozapine. Minocycline has novel and interesting molecular effects, including AMPA receptor modulation and anti-inflammatory and neuroprotective effects, which suggest it may have a significant role in treatment of neurologic and psychiatric disorders. Minocycline is currently available generically; its side effects are well-described and minimal. The proposed 10-week double-blind randomized treatment study seeks to demonstrate that adjunctive minocycline offers patients superior efficacy for persistent positive symptoms, cognitive impairments, and/or other components of schizophrenia pathology. This knowledge could lead to the more effective treatment of patients with schizophrenia. This novel research itself may lead to a better understanding of the pathophysiology of positive symptoms and cognitive impairments, which could contribute to improved treatments in the future. In addition we will examine the effects of minocycline on inflammatory cytokines and the mediating effects these may have in symptom improvement. PUBLIC HEALTH RELEVANCE: Little evidence is available to guide treatment in people with schizophrenia with persistent symptoms despite clozapine treatment. Preliminary data suggests that minocycline may be effective in clozapine treated patients, possibly through its modulation of the glutamate (AMPA) system and its effects on inflammatory cytokines. This study examines adjunct minocycline vs. placebo in a double blind randomized trial for people with schizophrenia who have persistent symptoms on clozapine. We will examine changes in symptomatology, neurocognitive functioning, inflammatory cytokines, and patient satisfaction/wellbeing.