Sycrest（阿塞那平）舌下含片用于治疗成年人Ⅰ型双相情感障碍中重度躁狂发作。
Sycrest是一种非典型抗精神病药物，此前已在美国以“Saphris”商品名上市。此次获批是基于近1 300例双相情感障碍躁狂症患者参与的临床试验数据。两项为期3周设计类似的随机、双盲、安慰剂或活性药物对照（奥氮平）的临床试验对Sycrest有效性进行了评价，结果显示，与安慰剂相比，Sycrest明显减少躁狂发作。双盲、非劣效性研究显示，用药9周，Sycrest的疗效可维持长达12周，且具有良好的安全性。一项涉及326例患者、为期12周的临床试验证实，Sycrest可以增强情绪稳定药锂或丙戊酸的疗效。

最常见的不良反应（＞10%）是嗜睡和焦虑，其他（1%~10%）包括：体重增加、食欲增加、肌张力障碍、静坐不能、运动障碍、帕金森病症状（运动迟缓、震颤）、眩晕、味觉障碍、肌肉僵硬、乏力等。

初次美国批准：2009

适应证和用途

SAPHRIS是一种不典型抗精神病药适用于：
精神分裂症的治疗。
在两项6-周临床试验中和一项维持试验成年中精神分裂症患者中确定疗效。
作为单药治疗或辅助治疗，伴随双极障碍I型的躁狂或混合发作的急性治疗。
在成年伴随双极障碍I型的躁狂或混合发作患者两项3-周单药试验和在一项3-周辅助试验中确定疗效。

剂量和给药方法

给药：不要吞咽片。SAPHRIS舌下片应放在舌下和让它完全溶解. 片将在数秒内溶解. 给药后10分钟应避免进食和饮.

剂型和规格
舌下片：5 mg和10 mg
舌下片，黑樱桃味：5 mg和10 mg

禁忌证
无

警告和注意事项
1）脑血管不良事件：用非典型抗精神病药治疗的痴呆-相关精神病老年患者曾见到脑血管不良事件发生率增加(如，中风，短暂缺血发作).
2）药物恶性综合征：用立即停药处理和严密监查。
3）迟发性运动障碍：如临床适宜停药。
4）高血糖和糖尿病：在有，和处在糖尿病风险患者常规监查葡萄糖.
5）体重增量：患者应接受常规体重监测。
6）直立性低血压和昏厥：可能发生眩晕，心动过速或心动过缓，和昏厥，特别是治疗早期。在有已知心7）血管或脑血管病患者中，和在未用过抗精神药物患者中慎用.
7）用抗精神病药曾报道白细胞减少，中性粒细胞减少，和粒细胞缺乏。有预先存在低白细胞计数(WBC)或白细胞减少/中性粒细胞减少史患者在治疗的头几个月期间频繁监查应有其完全细胞计数(CBC)和在缺乏其它原因第一次WBC下降征象时应停止SAPHRIS。
8）QT延长：QT间期增加；也延长QT间期的药物和有QT间期延长风险因子患者避免使用。
9）癫痫发作：有癫痫发作史或有癫痫发作阈降低情况患者中慎用。
10）潜在的认知和运动障碍：当操作机械时慎用。
11）自杀：精神分裂症和双相障碍自杀意图的可能性是固有的。密切监督高风险的患者。

不良反应
常观察到不良反应 (发生率 ≥5%和至少是2倍于安慰剂:
1）精神分裂症患者：静坐不能，口腔感觉减退，和嗜睡。
2）有双相障碍患者：嗜睡，眩晕，锥体束外的症状除了静坐不能，和体重增加。
3）双极障碍(辅助)：嗜睡和口腔感觉减退。

药物相互作用
氟伏沙明(强CYP1A2抑制剂)和帕罗西汀[Paroxetine](CYP2D6底物和抑制剂): 谨慎与SAPHRIS同时给药。

在特殊人群中使用
1）妊娠：妊娠时只有如果潜在效益正当胜过潜在风险才在期间使用SAPHRIS。
2）哺乳母亲：不推荐哺乳喂养。
3）儿童使用：尚未确定安全性和有效性。
4）肾损伤：无需剂量调整.
5）肝损伤: 不推荐在严重肝损伤患者中用SAPHRIS (Child-Pugh C).

剂型和规格

1）SAPHRIS 5 mg片是圆形，白至淡白舌下片，一侧有“5”字。
2）SAPHRIS 10 mg片是圆形，白至淡白舌下片，一侧有“10”字。
3）SAPHRIS 5-mg片，黑樱桃味，是圆形，白至淡白舌下片，一侧有圆环内“5”字。
4）SAPHRIS 10-mg片，黑樱桃味，是圆形，白至淡白舌下片，一侧有圆环内“10”字。.

Sycrest (sublingual asenapine) for acute mania

Sycrest (asenapine) is a new atypical antipsychotic licensed for the treatment of acute manic or mixed episodes in bipolar disorder.

Sycrest (asenapine) can be used as monotherapy or in combination with other agents

PHARMACOLOGY

Asenapine is an atypical antipsychotic that acts as an antagonist at dopaminergic, serotonergic and alpha-adrenergic receptors. Although the exact mechanism of action is not understood, its activity at D2 and 5-HT2A receptors is thought to be important in treating bipolar disorder. Actions at 5-HT1A, 5-HT1B, 5-HT2C, 5-HT6, 5-HT7, D3 and alpha2-adrenergic receptors may also contribute to the therapeutic effect. Unlike many other antipsychotics, asenapine has a low affinity for muscarinic receptors, which may be beneficial in patients where antimuscarinic effects are undesirable.1

The bioavailability of asenapine administered orally is low (2%), owing to extensive first-pass metabolism. When formulated as a sublingual tablet, asenapine is rapidly absorbed and achieves peak plasma concentrations within 90 minutes. To ensure optimal absorption, the manufacturer recommends avoiding eating or drinking for 10 minutes after the tablet has completely dissolved.1
   
CLINICAL STUDIES

The short-term efficacy of asenapine in the treatment of acute manic or mixed episodes in bipolar I disorder was evaluated in two 3-week randomised, double-blind phase 3 trials of similar design, which included placebo and olanzapine as controls. Patients with rapid cycling were excluded from both studies.1–3

Following a placebo run-in period, participants were randomised to receive flexible-dose sublingual asenapine (10mg twice daily on day 1, then 5mg or 10mg twice daily), oral olanzapine (15mg once daily on day 1, then 5–20mg once daily) or placebo. Young Mania Rating Scale (YMRS) was assessed at baseline and at day 21 as the primary efficacy measure.2,3

In the first study (n=488), patients receiving asenapine showed a significantly greater reduction in YMRS score as early as day 2 compared with patients on placebo (-3.0 vs -1.5; p<0.01), and this difference was maintained at day 21 (-10.8 vs -5.5; p≤0.0001).2 Similar results were observed in the second study (n=489), with a significantly greater reduction in YMRS score for asenapine than placebo after 2 days (-3.2 vs -1.7; p=0.022) and at 21 days (-11.5 vs -7.8; p<0.007).3

Olanzapine was also significantly more effective than placebo at days 2 and 21 in both studies. The studies were not designed to directly compare asenapine and olanzapine.2,3

Patients who completed either short-term study were eligible to join a double-blind 9-week extension study investigating the longer term safety and efficacy of asenapine. A total of 504 patients were enrolled and continued their assigned treatment with asenapine or olanzapine; those originally assigned to receive placebo were switched to asenapine. The treatment effect was maintained, with asenapine displaying non-inferiority to olanzapine in terms of reduction in YMRS score after 12 weeks (-24.4 vs -23.9).4

Asenapine was generally well tolerated in the trials, with the most common adverse events being somnolence, dizziness and sedation. Extrapyramidal symptoms were observed more frequently in patients receiving asenapine than in those receiving olanzapine. However, weight gain was more common and more pronounced with olanzapine than asenapine. The effects of asenapine on blood glucose and lipids were minimal.2–4.