Centre Hospitalier Universitaire, Clermont-Ferrand, France.
Ther Clin Risk Manag. 2011;7:239-50. doi: 10.2147/TCRM.S12701. Epub 2011 Jun 27.
Lurasidone is a new second-generation antipsychotic approved in October 2010 by the Food and Drug Administration for the treatment of schizophrenia. Like other second-generation antipsychotics, lurasidone is a powerful antagonist of D(2) dopamine and 5HT(2A) serotonin receptors, but differs from the other second-generation antipsychotics in its action profile for certain receptors. Lurasidone is the second-generation antipsychotic with the greatest affinity for 5HT(7) receptors and has a high affinity for 5HT(1A) serotonin receptors, compatible with favorable effects on cognitive function and an antidepressant action. By contrast, lurasidone has a low affinity for and α(1) α(2C)-adrenergic and 5HT(2C) serotonin receptors, and no affinity for histaminergic H(1) or muscarinic M(1) receptors, suggesting a better tolerability profile than the other second-generation antipsychotics. Lurasidone has demonstrated its efficacy in several short-term trials in acute schizophrenia, promptly and significantly reducing total Positive and Negative Syndrome Scale and Brief Psychiatric Rating Scale scores compared with placebo. Several long-term studies are in progress to assess its efficacy in the maintenance treatment of schizophrenic patients. The efficacy of lurasidone with regard to cognitive functions and depressive symptoms seems good, but requires further work. Lurasidone differs from the other second-generation antipsychotics by having a good tolerability profile, in particular for cardiometabolic tolerability. However, it seems to have a significant although moderate link with the occurrence of akathisia, extrapyramidal symptoms, and hyperprolactinemia at the start of treatment. This tolerance profile greatly broadens the scope of second-generation antipsychotics and so supports the view of some authors that the term "second-generation antipsychotic" is now outdated. Other therapeutic perspectives of lurasidone are assessed here, in particular bipolar depression.
鲁拉西酮是一种新型的第二代抗精神病药物，于 2010 年 10 月获得美国食品和药物管理局批准，用于治疗精神分裂症。与其他第二代抗精神病药物一样，鲁拉西酮是一种强有力的 D2 多巴胺和 5HT2A 血清素受体拮抗剂，但在某些受体的作用谱上与其他第二代抗精神病药物不同。鲁拉西酮是对 5HT7 受体具有最大亲和力的第二代抗精神病药物，对 5HT1A 血清素受体具有高亲和力，与认知功能的改善和抗抑郁作用兼容。相比之下，鲁拉西酮对α1α2C-肾上腺素能和 5HT2C 血清素受体的亲和力较低，对组胺能 H1 和毒蕈碱 M1 受体没有亲和力，这表明其耐受性比其他第二代抗精神病药物更好。鲁拉西酮在几项急性精神分裂症的短期试验中证明了其疗效，与安慰剂相比，迅速显著降低了阳性和阴性综合征量表和简明精神病评定量表的总分。目前正在进行几项长期研究，以评估其在精神分裂症患者维持治疗中的疗效。鲁拉西酮在认知功能和抑郁症状方面的疗效似乎很好，但需要进一步研究。鲁拉西酮与其他第二代抗精神病药物的不同之处在于其具有良好的耐受性，特别是在心脏代谢方面。然而，它似乎与治疗开始时静坐不能、锥体外系症状和高催乳素血症的发生有显著但中等程度的关联。这种耐受性谱极大地拓宽了第二代抗精神病药物的范围，因此支持了一些作者的观点，即“第二代抗精神病药物”这一术语现在已经过时。这里评估了鲁拉西酮的其他治疗前景，特别是双相情感障碍中的抑郁。
