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利鲁唑治疗情绪和焦虑障碍

Riluzole in the treatment of mood and anxiety disorders.

作者信息

Pittenger Christopher, Coric Vladimir, Banasr Mounira, Bloch Michael, Krystal John H, Sanacora Gerard

机构信息

Clinical Neuroscience Research Unit, Yale University School of Medicine, New Haven, Connecticut, USA.

出版信息

CNS Drugs. 2008;22(9):761-86. doi: 10.2165/00023210-200822090-00004.

Abstract

Recent advances implicate amino acid neurotransmission in the pathophysiology and treatment of mood and anxiety disorders. Riluzole, which is approved and marketed for the treatment of amyotrophic lateral sclerosis, is thought to be neuroprotective through its modulation of glutamatergic neurotransmission. Riluzole has multiple molecular actions in vitro; the two that have been documented to occur at physiologically realistic drug concentrations and are therefore most likely to be clinically relevant are inhibition of certain voltage-gated sodium channels, which can lead to reduced neurotransmitter release, and enhanced astrocytic uptake of extracellular glutamate.Although double-blind, placebo-controlled trials are lacking, several open-label trials have suggested that riluzole, either as monotherapy or as augmentation of standard therapy, reduces symptoms of obsessive-compulsive disorder, unipolar and bipolar depression, and generalized anxiety disorder. In studies of psychiatrically ill patients conducted to date, the drug has been quite well tolerated; common adverse effects include nausea and sedation. Elevation of liver function tests is common and necessitates periodic monitoring, but has been without clinical consequence in studies conducted to date in psychiatric populations. Case reports suggest utility in other conditions, including trichotillomania and self-injurious behaviour associated with borderline personality disorder. Riluzole may hold promise for the treatment of several psychiatric conditions, possibly through its ability to modulate pathologically dysregulated glutamate levels, and merits further investigation.

摘要

近期进展表明氨基酸神经传递在情绪和焦虑障碍的病理生理学及治疗中发挥作用。利鲁唑已获批准用于治疗肌萎缩侧索硬化症并投放市场,其被认为通过调节谷氨酸能神经传递而具有神经保护作用。利鲁唑在体外具有多种分子作用;已证实在生理现实的药物浓度下会发生的两种作用,因此最有可能与临床相关的是抑制某些电压门控钠通道,这可导致神经递质释放减少,以及增强星形胶质细胞对细胞外谷氨酸的摄取。尽管缺乏双盲、安慰剂对照试验,但多项开放标签试验表明,利鲁唑无论是作为单一疗法还是作为标准疗法的增效剂,均可减轻强迫症、单相和双相抑郁症以及广泛性焦虑症的症状。在迄今为止对精神病患者进行的研究中,该药物耐受性良好;常见不良反应包括恶心和镇静。肝功能检查升高很常见,需要定期监测,但在迄今为止针对精神科人群进行的研究中尚未产生临床后果。病例报告表明其在其他病症中也有应用价值,包括拔毛癖和与边缘型人格障碍相关的自伤行为。利鲁唑可能有望用于治疗多种精神疾病,可能是通过其调节病理性失调的谷氨酸水平的能力,值得进一步研究。

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