ST LOUIS (MD Consult) - Forest Laboratories, Inc, has announced that the US Food and Drug Administration (FDA) has approved the company's supplemental new drug application (sNDA) for Lexapro (escitalopram oxalate) for the acute and maintenance treatment of major depressive disorder (MDD) in adolescents 12 to 17 years old.

Lexapro is the second antidepressant to be approved for treating MDD in adolescents. MDD affects approximately 2 million adolescents in the United States, according to a recent national survey conducted by the Substance Abuse and Mental Health Services Administration.

The approval of Lexapro for adolescent depression was supported by two placebo-controlled studies, one conducted in adolescent patients taking Lexapro and one conducted in children and adolescents taking citalopram. The 8-week flexible-dose, placebo-controlled study, reported in 2008, compared Lexapro 10-20 mg/d to placebo in 12- to 17-year-old patients. Lexapro showed statistically significant greater mean improvement from baseline, compared to placebo, on the Children's Depression Rating Scale-Revised (CDRS-R).

In another 8-week, flexible-dose, placebo-controlled study, children and adolescents 7 to 17 years old treated with racemic citalopram 20 to 40 mg/d showed statistically significant greater mean improvement from baseline on the CDRS-R compared to patients treated with placebo. The positive results for this trial largely came from the adolescent subgroup. The FDA's determination of the efficacy of Lexapro in the acute treatment of MDD in adolescents was established, in part, on the basis of extrapolation from this study.

Two additional flexible-dose, placebo-controlled MDD studies were conducted: one Lexapro study in patients aged 7 to 17 and one citalopram study in adolescents. Neither study demonstrated efficacy on the primary efficacy parameter.

Although maintenance effectiveness in adolescent patients has not been systematically evaluated, the FDA in its review concluded that maintenance efficacy can be extrapolated from adult data along with comparisons of escitalopram pharmacokinetic parameters in adults and adolescent patients.

Lexapro was generally well tolerated. The overall profile of adverse reactions in pediatric patients was generally similar to that seen in adult studies and is described in the package insert.

"Adolescent depression can often be challenging to treat because there are limited treatment options that are proven to be effective and well-tolerated in this patient population," said Graham Emslie, MD, professor of psychiatry at the University of Texas Southwestern Medical Center in Dallas. "The FDA approval of Lexapro for adolescents is a significant development for the patients who struggle with this illness every day."

Depression and adolescents

Adolescent depression is characterized by persistent sadness or irritability or loss of interest in usual activities. For adolescents with depression, talk therapy and medication can play an important role in management of the illness. Patients on antidepressant treatment should also be closely monitored by health care providers, family members, and other caregivers.

About Lexapro

Lexapro is indicated for the acute and maintenance treatment of MDD in adults and adolescents (aged 12-17) and for acute treatment of generalized anxiety disorder in adults. Lexapro is thought to work by helping to restore the brain's chemical balance. It is believed to increase the availability of serotonin, a substance in the brain thought to influence mood. Since its launch in 2002, Lexapro has been prescribed to more than 18 million patients in the United States.

Safety information

Antidepressants increased the risk compared with placebo of suicidal thinking and behavior in children, adolescents, and young adults in short-term studies of MDD and other psychiatric disorders. Anyone considering prescribing Lexapro or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need.

Short-term studies did not show an increase in the risk of suicidality with antidepressants compared with placebo in adults beyond age 24. There was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior, especially during the initial few months of therapy or at times of dose changes.

This risk may persist until significant remission occurs. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Lexapro is not approved for use in pediatric patients younger than 12 years.
 

圣路易斯(MD Consult)——Forest Laboratories公司宣布，Lexapro(草酸艾司西酞普兰，来士普)的补充新药上市申请(sNDA)获美国食品和药物管理局(FDA)批准，用于治疗12～17岁青少年的重度抑郁症。

 

Lexapro是FDA批准的第2个用于治疗青少年重度抑郁症患者的药物。根据美国物质滥用与心理卫生服务部(SAMHSA)的调查，重度抑郁症困扰着美国大约200万青少年患者。

 

Lexapro获准用于治疗青少年抑郁症是基于2项安慰剂对照的临床研究结果，受试对象其中1项试验为服用Lexapro的青少年患者，另1项为服用西酞普兰的儿童和青少年患者。2008年报道的1项研究为期8周，受试者年龄在12～17岁，每天本品的服用剂量在10～20 mg，剂量可根据患者情况进行调整。本研究的结果表明，服用本品后《儿童抑郁量表》(修订版)(CDRS-R)分数与基线值相比，改善情况明显优于安慰剂对照组，且具有显著的统计学意义。

 

另1项研究为消旋的西酞普兰与安慰剂的对照研究，该研究同样也为期8周，患者的年龄从7～17岁，每天的西酞普兰服用剂量在20～40 mg。剂量可根据患者情况进行调整。结果表明，与安慰剂相比，服用西酞普兰后，患者CDRS-R 分数与基线值相比的改善程度具有显著的统计学意义。FDA作出Lexapro有效的决定，很大程度上来自该研究的类推结果。

 

此外还进行了另外2项安慰剂对照、剂量可调的重度抑郁症临床研究，其中1项纳入对象为年龄为7～17岁服用Lexapro的患者，另一项纳入对象为服用西酞普兰的患者。试验结果在主要疗效参数方面均显示其具有有效性。

 

目前尚无Lexapro用于青少年重度抑郁症维持治疗的系统评估研究，FDA批准其用于青少年重度抑郁症的维持治疗是将本品在成年患者中维持治疗的有效性进行类推的结果。此外，FDA还参考了本品在成年患者和青少年患者中的药代动力学参数情况。

 

Lexapro具有很好的耐受性，在青少年患者中的所有不良反应与在成年患者的出现的不良反应类似，并在药品包装说明书中做了叙述。

“青少年抑郁症治疗的药物选择通常会因为要考虑药物的有效性和耐受性而受到限制，”美国得克萨斯州大学西南医学中心的精神病学教授Graham Emslie博士说，“对于每天同病魔斗争的青少年抑郁患者而言，FDA批准本品有巨大的益处。”

 

抑郁症和青少年

 

青少年抑郁症临床特征包括持续的悲伤或烦躁情绪，对日常活动失去兴趣。谈话和药物均可对青少年抑郁症发挥重要治疗作用。医护人员、亲属及其他照护者也应对患者接受抗抑郁药治疗的过程进行密切监测。

 

关于Lexapro

 

Lexapro目前被批准用于年龄在12～17岁青少年重度抑郁患者的急性期治疗和维持治疗，还用于广泛焦虑症成年患者的治疗。其通过修复大脑内化学物质的平衡而起作用，可以增加大脑内控制情绪的关键物质——5-羟色胺的活性。自2002年推出以来，已有1,800万美国患者使用本药进行治疗。

 

关于安全性

 

在对重度抑郁症和其他精神疾患的短期研究中发现，抗抑郁药与安慰剂相比，增加了儿童、青少年和青年人的自杀念头和付诸实施的风险。对上述对象开具Lexapro或其他抗抑郁药处方时，必须要对该方面风险与临床需求进行均衡考虑。

 

短期研究显示抗抑郁药物与安慰剂相比，并没有增加24岁以上成年患者的自杀倾向风险。对于65岁以上的老年患者，使用抗抑郁药的自杀风险比安慰剂低。抑郁症和其他一些精神疾病本身就和自杀风险增加相关。对所有使用抗抑郁药治疗的各年龄阶段患者，都应密切对临床恶化、自杀倾向或不正常的行为改变而进行适当监测，特别是在治疗的最初几个月及调整剂量的时候。

 

这种自杀风险可能在症状发生显著缓解之前持续存在。开处方时应告知亲属和照护者必须进行密切监视。Lexapro未获准用于年龄小于12岁的儿童患者。