Franklin Rachel, Zorowitz Sam, Corse Andrew K, Widge Alik S, Deckersbach Thilo
Division of Neurotherapeutics, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA.
Neuropsychiatr Dis Treat. 2015 Aug 19;11:2143-52. doi: 10.2147/NDT.S50961. eCollection 2015.
Bipolar disorder (BD) is a debilitating and difficult-to-treat psychiatric disease that presents a serious burden to patients' lives as well as health care systems around the world. The essential diagnostic criterion for BD is episodes of mania or hypomania; however, the patients report that the majority of their time is spent in a depressive phase. Current treatment options for this component of BD have yet to achieve satisfactory remission rates. Lurasidone is a drug in the benzisothiazole class approved by the US Food and Drug Administration in June 2013 for the acute treatment of bipolar depression. Its pharmacological profile features high-affinity antagonism at D2, 5-HT2A, and 5-HT7 receptors; moderate-affinity antagonism at α2C-adrenergic receptors; low- to very low-affinity antagonism at α1A-adrenergic, α2A-adrenergic, H1, M1, and 5-HT2C receptors; and high-affinity partial agonism at 5-HT1A. Preliminary findings from two recent double-blinded clinical trials suggest that lurasidone is efficacious in treating bipolar I depression, with clinical effects manifesting as early as the first 2-3 weeks of treatment (as measured by the Montgomery-Åsberg Depression Rating Scale and Clinical Global Impressions Scale for use in bipolar illness). Its therapeutic benefit appears to be comparable to the current US Food and Drug Administration-indicated treatments: quetiapine and olanzapine-fluoxetine, according to a measure of effect size known as number needed to treat. These studies reported relatively limited extrapyramidal and metabolic side effects as a result of treatment with lurasidone, with the most common side effect being nausea. Safety data drawn from these studies, as well as a more extensive body of schizophrenia research, indicate that in comparison with other atypical antipsychotics, treatment with lurasidone is less likely to result in metabolic side effects such as weight gain or disturbances of serum glucose or lipid levels. Lurasidone holds clinical potential as a novel, efficacious pharmacological treatment for bipolar depression. However, current data on its use for the treatment of BD are limited, and more extensive research, both longer in duration as well as independently conducted, is needed.
双相情感障碍(BD)是一种使人衰弱且难以治疗的精神疾病,给世界各地患者的生活以及医疗保健系统带来了沉重负担。BD的基本诊断标准是躁狂或轻躁狂发作;然而,患者报告称他们大部分时间处于抑郁阶段。目前针对BD这一症状的治疗方案尚未达到令人满意的缓解率。鲁拉西酮是一种苯并异噻唑类药物,于2013年6月获美国食品药品监督管理局批准用于双相抑郁的急性治疗。其药理学特性表现为对D2、5-HT2A和5-HT7受体具有高亲和力拮抗作用;对α2C肾上腺素能受体具有中等亲和力拮抗作用;对α1A肾上腺素能、α2A肾上腺素能、H1、M1和5-HT2C受体具有低至极低亲和力拮抗作用;对5-HT1A具有高亲和力部分激动作用。最近两项双盲临床试验的初步结果表明,鲁拉西酮对治疗双相I型抑郁有效,临床效果最早在治疗的前2至3周就会显现(通过蒙哥马利-阿斯伯格抑郁评定量表和双相情感障碍临床总体印象量表测量)。根据一种名为治疗所需人数的效应量衡量标准,其治疗效果似乎与美国食品药品监督管理局目前批准的治疗药物喹硫平和奥氮平-氟西汀相当。这些研究报告称,鲁拉西酮治疗导致的锥体外系和代谢副作用相对有限,最常见的副作用是恶心。从这些研究以及更广泛的精神分裂症研究中得出的安全性数据表明,与其他非典型抗精神病药物相比,使用鲁拉西酮治疗导致体重增加或血糖或血脂水平紊乱等代谢副作用的可能性较小。鲁拉西酮作为一种新型、有效的双相抑郁药物治疗方法具有临床潜力。然而,目前关于其用于治疗BD的数据有限,需要进行更广泛、持续时间更长且独立开展的研究。