Adjunctive Minocycline in Clozapine Treated Patients for Psychosis and Cognition

描述（由申请人提供）：超过60%接受氯氮平治疗的患者持续出现症状和认知障碍，很少有数据支持循证建议来指导临床医生治疗这些患者。最近的数据表明，二甲胺四环素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。米诺环素具有新颖而有趣的分子效应，包括AMPA受体调节、抗炎和神经保护作用，这表明它可能在神经和精神疾病的治疗中发挥重要作用。米诺环素目前是通用的；它的副作用描述得很好，而且很小。拟议的为期10周的双盲随机治疗研究旨在证明辅助二甲胺四环素对持续阳性症状、认知障碍和/或精神分裂症病理的其他组成部分提供了卓越的疗效。这一知识可能会导致更有效地治疗精神分裂症患者。这项新研究本身可能会导致更好地理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，我们将研究二甲胺四环素对炎症细胞因子的影响以及这些可能在症状改善中的介导作用。

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.