近日，新型抗抑郁药物Trintellix（vortioxetine，沃替西汀）在美国推出，该药每日口服一次，用于重度抑郁症（MDD）成人患者的治疗。
注：之前的品牌名为Brintellix将更改为Trintellix
批准日期：2016年5月   公司：武田（Takeda）及灵北（Lundbeck）
TRINTELLIX（沃替西汀 vortioxetine）片剂，用于口服使用
最初美国批准：2013
警告：
自杀的想法和完整的黑框警告BEHAVIORSSee完整处方信息。
•在儿童，青少年和年轻成年人服用抗抑郁药自杀想法和行为的风险增加。
•监测恶化，自杀念头和行为的出现。
•TRINTELLIX尚未评估用于儿科患者。
目前的主要变化
警告和注意事项 7/2014
作用机理
的vortioxetine的抗抑郁作用的机理尚不完全清楚，但被认为是通过抑制血清素（5-HT）再摄取的与它增强在CNS血清素的活性。它也具有其他一些活动，包括5-HT3受体拮抗剂和5-HT1A受体激动。这些活动的到vortioxetine的抗抑郁作用的贡献尚未确立。
适应症和用法
TRINTELLIX的适应症为抑郁症（MDD）的治疗。
用法用量
•推荐的起始剂量为10毫克，每天一次口服，不考虑饭菜。
•剂量然后应提高到20毫克/天，如耐受。
•考虑5毫克/天，谁不耐受高剂量的患者。
•TRINTELLIX可以突然停药。然而，建议剂量15毫克/天或20mg /天的，如果可能减少到10毫克/天一周全停止之前。
•最大推荐剂量为10毫克/天已知的CYP2D6弱代谢。
剂型和规格
TRINTELLIX可作为5毫克，10毫克，15毫克和20毫克立即释放片剂。
禁忌症
•过敏者vortioxetine或TRINTELLIX制定的任何组件。
•单胺氧化酶抑制剂（单胺氧化抑制剂）：不要使用单胺氧化抑制剂用于治疗与TRINTELLIX或内的TRINTELLIX停止21天的治疗精神疾病。不要在停车用来治疗精神疾病的单胺氧化酶的14天内使用TRINTELLIX。此外，不要在谁是被利奈唑胺或静脉注射亚甲蓝治疗的患者开始TRINTELLIX。
警告和注意事项
•羟色胺综合征已报告与血清素能抗抑郁药（SSRIs的，SNRIs的，及其他），包括与TRINTELLIX，既当单独存在时，尤其是当共同给予与其他血清素剂（包括曲坦，三环抗抑郁药，芬太尼，锂，曲马多，色氨酸，丁螺环酮，和圣约翰草）。如果出现这样的症状，请停止TRINTELLIX并开始支持治疗。如与其他药物血清素的TRINTELLIX同时使用在临床上合理的，患者应该知道血清素综合征的潜在风险增加，尤其是在治疗开始和剂量的增加而增加。
•与血清素能抗抑郁药（SSRIs的，SNRIs的，及其他）的治疗可以提高异常出血的危险性。患者应告诫时TRINTELLIX是共施用与非甾体抗炎药（NSAIDs），阿司匹林，或影响凝血的其他药物的出血的危险性增加。
•工坊/轻躁狂的激活，抗抑郁治疗发生。屏幕患者躁郁症。
•闭角型青光眼：闭角型青光眼发生的患者抗抑郁药治疗的解剖未经窄房角。
•低钠血症可出现抗利尿激素分泌（SIADH）的综合症协会。
不良反应
最常见的不良反应（发生率≥5％和至少两次安慰剂的速率）分别为：恶心，便秘，呕吐。
药物相互作用
•CYP2D6的强抑制剂：当强CYP2D6抑制剂（例如，安非他酮，氟西汀，帕罗西汀，或奎尼定）的联合给药减少一半TRINTELLIX剂量。
•强大的CYP诱导剂：可考虑增加TRINTELLIX剂量当强CYP诱导剂（如利福平，卡马西平，苯妥英钠或）被合用超过14天。最大推荐剂量不应超过原剂量的3倍。
特殊人群中使用
•妊娠：根据动物实验数据，TRINTELLIX可能引起胎儿危害。
•哺乳母亲：请停止TRINTELLIX或哺乳。

Brintellix, Trintellix, vortioxetine (formerly Lu AA21004)
Important Safety Information for TRINTELLIX (vortioxetine)
WARNING: SUICIDAL THOUGHTS AND BEHAVIORS
Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term studies. These studies did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in patients over age 24; there was a trend toward reduced risk with antidepressant use in patients aged 65 and older.
In patients of all ages who are started on antidepressant therapy, monitor closely for worsening, and for emergence of suicidal thoughts and behaviors. Advise families and caregivers of the need for close observation and communication with the prescriber.
TRINTELLIX has not been evaluated for use in pediatric patients.
CONTRAINDICATIONS
Hypersensitivity: Hypersensitivity to vortioxetine or any components of the TRINTELLIX formulation. Angioedema has been reported in patients treated with TRINTELLIX.
Monoamine Oxidase Inhibitors (MAOIs): Due to an increased risk of serotonin syndrome, do not use MAOIs intended to treat psychiatric disorders with TRINTELLIX or within 21 days of stopping treatment with TRINTELLIX. Do not use TRINTELLIX within 14 days of stopping an MAOI intended to treat psychiatric disorders. Do not start TRINTELLIX in a patient who is being treated with linezolid or intravenous methylene blue.
WARNINGS AND PRECAUTIONS
Clinical Worsening and Suicide Risk: All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality (anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and mania), especially if these symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms. Families and caregivers of patients being treated with antidepressants for MDD or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients daily.
Serotonin Syndrome: The development of a potentially life-threatening serotonin syndrome has been reported with serotonergic antidepressants (SNRIs, SSRIs, and others), including TRINTELLIX, when used alone but more often when used concomitantly with other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John's Wort), and with drugs that impair metabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue). Serotonin syndrome symptoms may include mental status changes (eg, agitation, hallucinations, delirium, and coma), autonomic instability (eg, tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (eg, tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (eg, nausea, vomiting, diarrhea). If such symptoms occur, discontinue TRINTELLIX and any concomitant serotonergic agents, and initiate supportive symptomatic treatment. If concomitant use of TRINTELLIX is clinically warranted, patients should be made aware of and monitored for potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases.
Abnormal Bleeding: Treatment with serotonergic antidepressants (SSRIs, SNRIs, and others) may increase the risk of abnormal bleeding. Patients should be cautioned about the increased risk of bleeding when TRINTELLIX is coadministered with NSAIDs, aspirin, or other drugs that affect coagulation.
Activation of Mania/Hypomania: Activation of mania/hypomania can occur with antidepressant treatment. Prior to initiating treatment with an antidepressant, screen patients for bipolar disorder. As with all antidepressants, use TRINTELLIX cautiously in patients with a history or family history of bipolar disorder, mania, or hypomania.
Angle-Closure Glaucoma: The pupillary dilation that occurs following use of many antidepressant drugs, including TRINTELLIX, may trigger an angle-closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy.
Hyponatremia: Hyponatremia has occurred as a result of serotonergic drugs and in many cases, appears to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Elderly patients and patients taking diuretics or who are otherwise volume-depleted can be at greater risk. More severe or acute cases have included hallucination, syncope, seizure, coma, respiratory arrest, and death. Discontinue TRINTELLIX in patients with symptomatic hyponatremia and initiate appropriate medical intervention.
Adverse Reactions: The most commonly observed adverse reactions for TRINTELLIX in 6- to 8-week placebo-controlled studies (incidence ≥ 5% and at least twice the rate of placebo) were by dose (5 mg, 10 mg, 15 mg, 20 mg) vs placebo: nausea (21%, 26%, 32%, 32% vs 9%), constipation (3%, 5%, 6%, 6% vs 3%), and vomiting (3%, 5%, 6%, 6% vs 1%).
Drug Interactions: Concomitant administration of TRINTELLIX and strong CYP2D6 inhibitors or strong CYP inducers may require a dose adjustment of TRINTELLIX.
Indication
TRINTELLIX is indicated for the treatment of major depressive disorder in adults.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1a5b68e2-14d0-419d-9ec6-1ca97145e838
TRINTELLIX Rx
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Generic Name and Formulations:
Vortioxetine 5mg, 10mg, 15mg, 20mg; tabs.
Company:
Takeda and Lundbeck

Select therapeutic use: Mood disorders
Indications for TRINTELLIX:
Treatment of major depressive disorder.

Adult:
Initially 10mg once daily; then, increase to 20mg/day, as tolerated. May consider 5mg/day if unable to tolerate. Discontinuing treatment: may reduce to 10mg/day for one week before full discontinuation of 15mg/day or 20mg/day. CYP2D6 poor metabolizers: max 10mg/day. Concomitant strong CYP2D6 inhibitors: reduce vortioxetine dose by ½; increase to original level when inhibitor is discontinued. If concomitant strong CYP inducers for >14 days: consider increasing vortioxetine dose up to max 3x original dose; reduce to original level within 14 days when inducer is discontinued.

Children:
<18yrs: not established.

Contraindications:
Concomitant MAOIs during or within 21 days of discontinuing vortioxetine. Within 14 days of discontinuing an MAOI. Concomitant linezolid or IV methylene blue.

Warnings/Precautions:
Increased risk of suicidal thinking and behavior in children, adolescents, and young adults; monitor for clinical worsening or unusual changes. Monitor for serotonin syndrome; discontinue if occurs. History of mania/hypomania. Screen for bipolar disorder prior to starting. Angle-closure glaucoma. Severe hepatic impairment: not recommended. Volume depletion. Elderly. Pregnancy (Cat.C; avoid 3rd trimester; see full labeling for effects on neonates). Nursing mothers: not recommended.

Interactions:
See Contraindications. Do not start with concomitant linezolid or IV methylene blue; if necessary, discontinue vortioxetine before starting; monitor for serotonin syndrome for 21 days or until 24hrs after last dose of linezolid or IV methylene blue, whichever comes first. Caution with concomitant triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, St. John's wort, linezolid, IV methylene blue; may cause serotonin syndrome. Increased risk of bleeding with NSAIDs, aspirin, warfarin, others that affect coagulation. May be affected by strong CYP2D6 inhibitors (eg, bupropion, fluoxetine, paroxetine, quinidine) or strong CYP inducers (eg, rifampicin, carbamazepine, phenytoin); adjust doses (see Adults). May potentiate protein-bound drugs.

Pharmacological Class:
Serotonergic agonist and antagonist.

Adverse Reactions:
Nausea, constipation, vomiting, dizziness; hyponatremia (esp. elderly), mania/hypomania, sexual dysfunction.

Note:
Formerly known as Brintellix.

How Supplied:
Tabs—30, 90, 500