ST LOUIS (MD Consult) - On July 1, 2009, the US Food and Drug Administration (FDA) announced that it is now requiring manufacturers of the smoking cessation aids varenicline (Chantix) and bupropion (Zyban and generics) to add boxed warnings to the drugs' labels that highlight the risk of serious neuropsychiatric symptoms. These symptoms include changes in behavior, hostility, agitation, depressed mood, suicidal thoughts and behavior, and attempted suicide. The FDA is also requiring the manufacturers to create medication guides for patients that contain warnings about this risk.

 

These same FDA requirements are also being applied to bupropion products (Wellbutrin and generics) that are indicated for the treatment of depression and seasonal affective disorder.

 

This FDA action was prompted by an analysis of data from a continued review of postmarketing adverse event reports for varenicline and bupropion the agency has received. (A summary of the data was published in the FDA Drug Safety Newsletter.2009;2[1]). These reports included events that demonstrated a temporal relationship between the use of varenicline or bupropion and suicidal events, as well as the occurrence of suicidal ideation and suicidal behavior in patients with no history of psychiatric disease. In most cases, neuropsychiatric symptoms occurred while taking the medication, but in others, symptoms arose after drug discontinuation. The FDA does admit that some of the reported cases may have been confounded by symptoms typically affecting persons who have stopped smoking and are experiencing nicotine withdrawal.

 

Patients should be informed that it is not unusual to have symptoms such as irritability, anxiety, depressed mood, and sleep difficulties when they are withdrawing from nicotine, independent of whether they are taking varenicline or bupropion. Patients and health care providers should be aware that persons with serious psychiatric illnesses such as schizophrenia, bipolar disorder, and major depressive disorder may experience worsening of their preexisting psychiatric illness while taking either of these drugs. Health care professionals are being asked to advise patients to discontinue varenicline or bupropion and seek immediate medical care if they experience agitation, depressed mood, and any changes in behavior that are atypical of nicotine withdrawal, or if they experience suicidal thoughts or behavior.

 

Patients who discontinue treatment with varenicline or bupropion because of neuropsychiatric events should continue to be monitored until their symptoms resolve. In many of the cases reported to the FDA, symptoms resolved after treatment was stopped. However, in some cases, neuropsychiatric symptoms persisted beyond that time.

 

The FDA believes that it is important to discuss the possibility of serious neuropsychiatric symptoms in the context of the benefits of quitting smoking before prescribing these medications to patients. Varenicline and bupropion have both been shown to be effective smoking cessation aids, and the health benefits of smoking cessation are immediate and substantial.

圣路易斯(MD Consult)——2009年7月1日，美国食品药物管理局(FDA)宣布，其目前正在要求戒烟辅助药物瓦伦尼克林(Chantix)与安非他酮(Zyban及其同类药)的制造商在药物标签中增加黑框警告，强调药物导致严重神经精神症状的风险。这些症状包括：行为改变、敌对行为、激动、情绪抑郁、自杀念头和行为以及企图自杀。FDA还要求这些制造商制订出包含警示该风险的患者用药指南。

FDA的这些要求也同样适用于安非他酮产品(Wellbutrin及其同类药)，这些药物适用于治疗抑郁症和季节性情感障碍。

FDA的这一举措是由一项数据分析所引发，这些数据来自FDA收到的关于瓦伦尼克林和安非他酮上市后不良事件报告的后续综述(发表于FDA Drug Safety Newsletter.2009;2[1])。这些不良事件报告包括既往无精神病史患者使用瓦伦尼克林或安非他酮与自杀事件，以及与自杀意念和自杀行为之间存在的短暂关联。大多数病例在服药时出现神经精神症状；但其他一些病例则在停药后出现神经精神症状。FDA也承认，有些报告情况可能与已停止吸烟并正经历尼古丁戒断者的典型症状相混淆。

当患者正在戒烟时，应告知他们，出现诸如烦躁、焦虑、情绪抑郁和睡眠困难的症状并不罕见，而且这些症状与他们是否正在服用瓦伦尼克林或安非他酮无关。患者及卫生工作者应认识到，患有严重精神疾病如精神分裂症、躁郁症以及严重抑郁症的患者在服用这两种药物时，可能出现其既往精神疾病加重现象。如果患者出现激动、抑郁情绪以及任何不典型的尼古丁戒断症状时，或者出现自杀念头或行为时，卫生工作者应建议患者停用瓦伦尼克林或安非他酮，并建议立刻进行医疗处理。

应继续监测因神经精神事件而停用瓦伦尼克林或安非他酮的患者，直到其症状消失。向FDA报告的许多病例在停止治疗后症状消失；然而，一些病例在停止治疗后神经精神症状持续存在。

FDA认为，在为患者开具这些药物处方之前，权衡戒烟所带来的益处与出现严重神经精神症状的可能性是非常重要的。瓦伦尼克林和安非他酮均是有效的戒烟辅助药物，戒烟所带来的健康益处是立竿见影的和实质性的。