2013年9月30日，美国食品药品管理局（FDA）批准Brintellix（Vortioxetine）用于治疗成人重型抑郁症。
重型抑郁症（MDD）的主要特征为心境改变及其他一系列的症状，对患者的工作能力、睡眠、学习、饮食及享受当下的快乐产生困扰。抑郁症状可在一生中多次复发，但部分患者也可能仅经历一次。
MDD的其它体征和症状包括对日常活动失去兴趣、体重或饮食发生明显变化、失眠或嗜睡、坐立不安/来回走动（激越）、疲劳、罪恶感或无价值感、思维迟缓、注意受损、自杀未遂或自杀想法。并非所有MDD患者均经历相同的症状。
“重型抑郁症具有致残性，使人不能正常工作，”FDA药物评价与研究中心精神病学产品部门代理主任、医学博士Mitchel lMathis称，“鉴于药物对个体的影响不同，所以抗抑郁治疗选择的多样化是很重要的。”
在6项临床研究中，MDD成人患者被随机给予Brintellix或安慰剂，这6项临床研究证实Brintellix可有效抗抑郁。另有一项临床研究显示，Brintellix降低了患者治疗后复发的可能性。这些研究在美国及其它国家完成。
据临床试验报道，Brintellix最常见的副作用包括恶心、便秘及呕吐。Brintellix片剂可供使用的规格有5mg、10mg、15mg和20mg。
Brintellix与其它抗抑郁药均有黑框警告及用药指南，以提醒患者和医生，这些抗抑郁药在初始治疗期间可能增加儿童、青少年及18至24岁青壮年自杀观念及行为的风险；而研究显示，24岁以上成年人的自杀风险似乎没有增加，而65岁及以上年龄成年患者的该风险或降低。开始抗抑郁治疗时，应严密监测患者的病情恶化及自杀行为。
Brintellix由武田制药与灵北制药共同上市销售。
批准日期： 2013年 9月30日；公司：Takeda Pharmaceutical 公司 Limited和H. Lundbeck A/S
BRINTELLIX (vortioxetine)片，为口服使用
美国初次批准：2013
适应证和用途
BRINTELLIX是适用为重度抑郁症(MDD)的治疗。
剂量和给药方法
（1）推荐开始剂量是10 mg口服给予每天1次不受食物影响。
（2）当耐受剂量应增加至20 mg/day。
（3）对不能耐受较高剂量患者考虑5 mg/day。
（4）BRINTELLIX可突然停药。 但是，建议如可能完全终止前1周15 mg/day或20 mg/day剂量减低至10mg/day。
（5）在已知CYP2D6代谢差患者中最大推荐剂量为10mg/day。
剂型和规格
可得到5mg，10mg，15mg,和20mg立即释放BRINTELLIX片。
禁忌证
（1）对vortioxetine或BRINTELLIX制剂任何组分超敏性。
（2）单胺氧化酶抑制剂(MAOIs)：不要意向使用MAOIs与BRINTELLIX或停止用BRINTELLIX治疗21天内治疗精神疾病。在一种MAOI停止14天内不要意向使用BRINTELLIX治疗精神疾病。此外，正在用利奈唑胺[linezolid]或静脉亚甲蓝[methylene blue]治疗患者不要开始BRINTELLIX (4)。
（1）用5-HT能抗抑郁药(SSRIs，SNRIs，和其他)，包括用BRINTELLIX，两者当单独用，但尤其是当与其他5-HT能药物共同给药时曾报道5-HT综合证(包括曲坦类药物[triptans]，三环类抗抑郁药[tricyclic antidepressants]，芬太尼[fentanyl]，锂[lithium]，曲马多[tramadol]，色氨酸，丁螺环酮[buspirone]，和圣约翰草[St. John's Wort])。如果出现这种症状，终止BRINTELLIX和开始支持治疗。如果临床上想要BRINTELLIX与其他5-HT药物的同时使用，患者应注意对5-HT综合证潜在风险增加，尤其是治疗开始和剂量增加期间。
（2）用5-HT能抗抑郁药治疗(SSRIs，SNRIs，和其他)可能增加异常出血的风险。当BRINTELLIX与非甾体抗炎药(NSAIDs)，阿司匹林[aspirin]，或影响凝血其他药物共同给药时患者应谨慎注意关于出血风险增加。
（3）抗抑郁药治疗可出现躁狂/轻躁狂的激活。筛选躁郁症患者。
（4）与抗利尿激素不适当分泌综合证(SIADH)可能伴发低钠血症。
不良反应
最常见不良反应(发生率 ≥5%和至少安慰剂率的2倍)是：恶心，便秘和呕吐。
药物相互作用
（1）CYP2D6的强抑制剂：当强CYP2D6抑制剂(如，安非他酮[bupropion]，氟西汀[fluoxetine]，帕罗西汀[paroxetine]，或奎尼丁[quinidine])被共同给药减低BRINTELLIX剂量一半。
（2）强CYP诱导剂：当一种强CYP诱导剂(如，利福平[rifampin]，卡马西平[carbamazepine]，或苯妥英钠[phenytoin])被共同给药共14天以上考虑增加BRINTELLIX剂量。最大推荐剂量不应超过原剂量3倍。
特殊人群中使用
（1）妊娠：根据动物资料，BRINTELLIX可能致胎儿危害。
（2）哺乳母亲：终止BRINTELLIX或终止哺乳。

Important Safety Information
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.
BRINTELLIX has not been evaluated for use in pediatric patients.
CONTRAINDICATIONS
Hypersensitivity: Hypersensitivity to vortioxetine or any components of the BRINTELLIX formulation. Angioedema has been reported in patients treated with BRINTELLIX.
Monoamine Oxidase Inhibitors (MAOIs): Due to an increased risk of serotonin syndrome, do not use MAOIs intended to treat psychiatric disorders with BRINTELLIX or within 21 days of stopping treatment with BRINTELLIX. Do not use BRINTELLIX within 14 days of stopping an MAOI intended to treat psychiatric disorders. Do not start BRINTELLIX 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 BRINTELLIX, 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 BRINTELLIX and any concomitant serotonergic agents, and initiate supportive symptomatic treatment. If concomitant use of BRINTELLIX 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 BRINTELLIX 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 BRINTELLIX cautiously in patients with a history or family history of bipolar disorder, mania, or hypomania.
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 BRINTELLIX in patients with symptomatic hyponatremia and initiate appropriate medical intervention.
Adverse Reactions: The most commonly observed adverse reactions for BRINTELLIX 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 BRINTELLIX and strong CYP2D6 inhibitors or strong CYP inducers may require a dose adjustment of BRINTELLIX.
Indication
BRINTELLIX is indicated for the treatment of major depressive disorder in adults.
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Takeda and Lundbeck Announce Brintellix® (vortioxetine) for the Treatment of Major Depressive Disorder in Adults is Now Available in Pharmacies
Deerfield, Ill., January 21, 2014 /PRNewswire/ – Takeda Pharmaceuticals U.S.A., Inc. (Takeda) and Lundbeck US jointly announced today that Brintellix (vortioxetine), for the treatment of major depressive disorder (MDD) in adults, is available in pharmacies across the United States (U.S.) – following initial availability through wholesalers soon after its September 30 approval by the U.S. Food and Drug Administration. Brintellix is a once-daily oral antidepressant available in a range of doses to help address the variability of patient needs.
“MDD continues to be a challenging condition to manage, and we are proud to make Brintellix available, as a new treatment option for people struggling with major depression,” said Douglas Cole, president, Takeda Pharmaceuticals U.S.A., Inc.
The comprehensive clinical trial program evaluating the safety and efficacy of Brintellix was comprised of seven positive pivotal studies, including six 6-8 week short-term studies and one 24-64 week long-term maintenance study that demonstrated statistically significant improvements in overall symptoms of depression in adults with MDD. The primary rating scales utilized in the short-term studies included mean change from baseline to endpoint in the Montgomery-Asberg Depression Rating Scale (MADRS) or the Hamilton Depression Rating Scale (HAMD-24) total score. In addition, the long-term maintenance study also showed Brintellix treatment resulted in a statistically significant longer time to recurrence of depressive episodes (defined as a MADRS total score greater than or equal to 22 or as judged by the investigator) compared to placebo.
“Our passion for helping people living with MDD has been the inspiration for advancing Brintellix from the laboratory through clinical studies, and now into the hands of those who need it,” said Staffan Schüberg, president, Lundbeck US. “This same passion fuels our ongoing commitment to supporting people with this often chronic and complex disease.”
Fewer than half of people with depression worldwide are treated, and the burden of depression is expected to continue to rise globally. In fact, clinical depression was the second-leading cause of global disability in 2010. In the U.S., it’s been estimated that more than 30 million people have suffered with MDD over a lifetime.1
Patients can visit www.Brintellix.com to sign up for additional information about this new treatment option.
About Brintellix (vortioxetine)
The mechanism of the antidepressant effect of Brintellix is not fully understood. It is an inhibitor of serotonin (5-HT) reuptake and that is thought to be a mechanism of its action. It is also an agonist at 5-HT1A receptors, a partial agonist at 5-HT1B receptors and an antagonist at 5-HT3, 5-HT1D and 5-HT7 receptors. The contribution of each of these activities to Brintellix’s antidepressant effect has not been established. It is considered to be the first and only compound with this combination of pharmacodynamic activity. The clinical relevance of this is unknown.
Brintellix was discovered by Lundbeck researchers in Copenhagen, Denmark. The clinical trial program in the U.S. was conducted jointly by Lundbeck and Takeda, and Takeda holds the new drug application for the U.S. market. Brintellix is a trademark of H. Lundbeck A/S and is used under license by Takeda Pharmaceuticals America, Inc.
The World Health Organization has issued an Anatomical Therapeutic Chemical (ATC) code for Brintellix that places it in the category of “Other” antidepressants.
The most commonly observed adverse events in MDD patients treated with Brintellix in 6-8 week placebo-controlled studies (incidence greater than or equal to 5 percent and at least twice the rate of placebo) were nausea, constipation and vomiting. Overall, 5 to 8 percent of the patients who received Brintellix 5 to 20 mg/day in short-term trials discontinued treatment due to an adverse reaction, the most common being nausea, compared with 4 percent of placebo-treated patients in these studies. Brintellix and other antidepressants may cause serious side effects. See Important Safety Information below.
In clinical studies, Brintellix had no significant effect on body weight as measured by the mean change from baseline in 6-8 week placebo-controlled studies. In the 6-month, double-blind, placebo-controlled phase of a long-term study in patients who had responded to Brintellix during the initial 12-week, open-label phase, there was no significant effect on body weight between Brintellix and placebo-treated patients. Brintellix has not been associated with any clinically significant effects on vital signs, including systolic and diastolic blood pressure and heart rate, as measured in placebo-controlled studies.
The recommended starting dose of Brintellix is 10 mg once daily without regard to meals. The dose should then be increased to 20 mg/day, as tolerated, because higher doses demonstrated better treatment effects in trials conducted in the U.S. A dose decrease down to 5 mg/day may be considered for patients who do not tolerate higher doses. The available doses provide important flexibility for physicians to help address the variability of patient needs.
Brintellix will be available as 5 mg, 10 mg and 20 mg tablets.
IMPORTANT SAFETY INFORMATION
Suicidal Thoughts or Actions
Antidepressants may increase suicidal thoughts or actions in some children, teens or young adults within the first few months of treatment or when the dose is changed. Depression or other serious mental illnesses are the most important causes of suicidal thoughts or actions. People who have (or have a family history of) bipolar illness, or suicidal thoughts or actions may have a particularly high risk. Pay close attention to any changes, especially sudden changes in mood, behavior, thoughts or feelings. Call your healthcare provider right away if symptoms such as anxiety, irritability, impulsivity, trouble sleeping, aggressive behavior or suicidal thoughts are new, worse or worry you. BRINTELLIX has not been evaluated for use in patients under 18.
Do not take BRINTELLIX if you:
•Are allergic to vortioxetine or any of the ingredients in BRINTELLIX
•Take a Monoamine Oxidase Inhibitor (MAOI). Ask your healthcare provider or pharmacist if you are not sure if you take an MAOI, including the antibiotic linezolid; do not take an MAOI within 21 days of stopping BRINTELLIX; do not start BRINTELLIX if you stopped taking an MAOI in the last 14 days
BRINTELLIX may cause serious side effects including:
Serotonin Syndrome: A potentially life-threatening problem that can happen when medicines such as BRINTELLIX are taken with certain other medicines. Symptoms may include agitation, hallucinations, coma or other changes in mental status; problems controlling movements or muscle twitching, stiffness or tightness; fast heartbeat, high or low blood pressure; sweating or fever; nausea, vomiting or diarrhea.
Abnormal bleeding or bruising: BRINTELLIX and other serotonergic antidepressant medicines may increase your risk of bleeding or bruising, especially if you take the blood thinner warfarin (Coumadin®, Jantoven®), a non-steroidal anti-inflammatory drug (NSAID), or aspirin.
Manic episode: Symptoms may include greatly increased energy; severe trouble sleeping; racing thoughts; reckless behavior; unusually grand ideas; excessive happiness or irritability; talking more or faster than usual.
Low salt (sodium) levels in the blood: Symptoms may include headache; difficulty concentrating, memory changes or confusion; weakness and unsteadiness on your feet; and in severe or sudden cases hallucinations, fainting, seizures or coma. If not treated, severe low sodium levels can cause death.
Before starting BRINTELLIX, tell your healthcare provider if you have or had liver problems, seizures or convulsions, bipolar disorder (manic depression) or mania, low salt (sodium) levels in your blood, bleeding problems, drink alcohol, have any other medical conditions or if you are pregnant, nursing, plan to become pregnant, or plan to nurse.
BRINTELLIX and some medicines may interact with each other, may not work as well, or may cause serious side effects when taken together. Tell your healthcare provider if you plan on or are taking any other prescription and non-prescription medicines, vitamins and herbal supplements including medicines for migraine headaches, such as triptans; medicines used to treat mood, anxiety, psychotic or thought disorders such as tricyclics, lithium, SSRIs, SNRIs, bupropion, buspirone or antipsychotics; MAOIs including linezolid (a specific antibiotic); over-the-counter supplements such as tryptophan or St. John’s wort; and the following medicines: aspirin, NSAIDs, warfarin (Coumadin®, Jantoven®), diuretics, rifampicin, carbamazepine, phenytoin, quinidine, tramadol or fentanyl
Common side effects of BRINTELLIX include: nausea, constipation or vomiting. These are not all the possible side effects of BRINTELLIX.
Do not start or stop taking BRINTELLIX without talking to your healthcare provider first. Suddenly stopping BRINTELLIX when you take higher doses may cause you to have side effects including headache, stiff muscles, mood swings, sudden outbursts or anger, dizziness or feeling lightheaded, or runny nose.
Until you know how BRINTELLIX affects you, do not drive, operate heavy machinery or engage in other dangerous activities.
Avoid drinking alcohol while taking BRINTELLIX.
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注：以下产品不同规格和不同价格。购买以咨询为准！
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产地国家: 美国
原产地英文商品名:
BRINTELLIX 5mg/tab 30tabs/box
原产地英文药品名:
VORTIOXETINE HYDROBROMIDE
中文参考商品译名:
BRINTELLIX 75毫克/片 30片/瓶
中文参考药品译名:
沃替西汀
生产厂家中文参考译名:
武田制药与灵北制药
生产厂家英文名:
Takeda Pharmaceuticals and Lundbeck Pharmaceuticals
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产地国家: 美国
原产地英文商品名:
BRINTELLIX 10mg/tab 30tabs/box
原产地英文药品名:
VORTIOXETINE HYDROBROMIDE
中文参考商品译名:
BRINTELLIX 10毫克/片 30片/瓶
中文参考药品译名:
沃替西汀
生产厂家中文参考译名:
武田制药与灵北制药
生产厂家英文名:
Takeda Pharmaceuticals and Lundbeck Pharmaceuticals
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产地国家: 美国
原产地英文商品名:
BRINTELLIX 20mg/tab 30Tablets/box
原产地英文药品名:
VORTIOXETINE HYDROBROMIDE
中文参考商品译名:
BRINTELLIX 20毫克/片 30片/瓶
中文参考药品译名:
沃替西汀
生产厂家中文参考译名:
武田制药与灵北制药
生产厂家英文名:
Takeda Pharmaceuticals and Lundbeck Pharmaceuticals