Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
CNS Neurosci Ther. 2011 Dec;17(6):645-8. doi: 10.1111/j.1755-5949.2010.00200.x. Epub 2010 Oct 15.
The second generation atypical antipsychotic, asenapine (Saphris), was approved by the US FDA (August 2009) for the acute treatment of manic or mixed episodes with or without psychotic features associated with bipolar I disorder in adults as well as the acute treatment of schizophrenia. Asenapine exhibits a high affinity for and antagonism at several serotonergic (5-HT(2A-C), 5HT(5A), 5HT(6), 5HT(7)), dopaminergic (D(2), D(3)), alpha-adrenergic (α(1) and α(2)), and histaminergic (H1, H2) receptor subtypes. Asenapine is the first atypical antipsychotic formulated as a fast-dissolving, rapidly absorbed sublingual tablet. Asenapine was evaluated in adults with bipolar I disorder, manic or mixed episodes with or without psychotic features. Two identically designed 3-week registration trials confirmed the efficacy of asenapine relative to placebo in studies that included olanzapine as an active control. The placebo-subtracted rate of EPS (excluding akathisia) is 5% whereas the placebo-subtracted rate of akathisia was 2%. The placebo-subtracted rate of clinically significant weight gain (≥7%) with asenapine was approximately 5% during the 3-week acute mania trials. A 9- extension trial indicated that 19% of asenapine patients will experience clinically significant weight gain. Clinically significant metabolic abnormalities were not observed during the acute and/or extension trials. Asenapine can be associated with somnolence (asenapine 24%, placebo 6%) and does not appear to be associated with clinically significant changes in vital signs, laboratory parameters, or electrocardiographic changes. Bipolar depression and recurrence prevention studies are required to fully characterize this novel agent's position in the treatment of bipolar disorder.
第二代非典型抗精神病药物阿塞那平（商品名：Saphris）于 2009 年 8 月获得美国食品药品监督管理局（FDA）批准，用于治疗成人伴有或不伴有精神病性特征的双相 I 型障碍躁狂或混合发作，以及精神分裂症的急性治疗。阿塞那平对几种血清素能（5-HT2A-C、5HT5A、5HT6、5HT7）、多巴胺能（D2、D3）、α-肾上腺素能（α1 和 α2）和组胺能（H1、H2）受体亚型具有高亲和力和拮抗作用。阿塞那平是第一个被制成快速溶解、快速吸收的舌下片剂的非典型抗精神病药物。阿塞那平已在双相 I 型障碍、伴有或不伴有精神病性特征的躁狂或混合发作的成人中进行了评估。两项设计相同的 3 周注册试验证实，与安慰剂相比，阿塞那平在包括奥氮平作为活性对照的研究中具有疗效。不包括静坐不能的 EPS（锥体外系症状）的安慰剂校正发生率为 5%，而静坐不能的安慰剂校正发生率为 2%。阿塞那平治疗 3 周急性躁狂试验中，体重显著增加（≥7%）的安慰剂校正发生率约为 5%。一项 9 周扩展试验表明，19%的阿塞那平患者会出现体重显著增加。在急性和/或扩展试验中未观察到临床显著的代谢异常。阿塞那平可能会引起嗜睡（阿塞那平 24%，安慰剂 6%），并且似乎不会导致生命体征、实验室参数或心电图变化的临床显著改变。需要进行双相抑郁症和复发预防研究，以充分描述该新型药物在双相障碍治疗中的地位。
