Everyone knows that smoking harms health and that the habit is difficult to quit. Unfortunately, some products that help people stop smoking can also be harmful – perhaps too harmful to consider using.
In June 2011, the U.S. Food and Drug Administration (FDA) announced new concerns about the safety of Chantix. Their announcement came in the months after two reports by independent researchers that there were more reports of deaths and violence from taking Chantix than any other drug.
These reports added to concerns about two stop-smoking drugs, Chantix and Zyban. In July 2009, the FDA had already announced “black box” warning labels on both drugs. A “black box” warning is the FDA’s most serious caution and indicates that a drug carries significant health risks. The black box warnings for Chantix and Zyban warn of the mental health risks associated with their use, which can include changes in behavior, depressed mood, hostility, and suicidal thoughts.
These warnings were recommended as the result of information gathered from clinical trials, as well as a series of reports to the FDA’s Adverse Event Reporting System. Zheng-Xiong Xi, MD, PhD, a researcher at the National Institute on Drug Abuse, found that Chantix was associated with incredibly dangerous side effects in many individuals, including suicide attempts and seizures, as well as psychosis, depression, and serious injuries resulting from dizziness, loss of consciousness, movement disorders, and visual disturbances.These problems have been noted among individuals with a history of mental illness but also have occurred among individuals with no prior history of mental illness.
Analysis from reports to the FDA’s Adverse Event Reporting System similarly shows that some people who used Chantix and Zyban began experiencing changes in behavior, depressed mood, and suicidal thoughts shortly after starting the medication. The symptoms usually ended shortly after the medication was stopped, but some people still reported symptoms after stopping the medications, while still others did not even begin developing the symptoms until after they stopped taking the drug.
Neither Chantix nor Zyban contains nicotine, unlike other smoking cessation aids such as chewing gum and the patch. Nicotine withdrawal can also cause mental health problems similar to those caused by Chantix and Zyban, such as depression, anxiety, irritability, restlessness, and sleep disturbance. However, the mental health risks of these two drugs far exceed the symptoms suffered by people with nicotine withdrawal.
Zyban is another name for Wellbutrin, an anti-depressant. Its marketing as a smoking-cessation drug came about after researchers noticed that smokers who took Wellbutrin for depression had less desire to smoke. GlaxoSmithKline carried out additional research in order to get approval to sell Wellbutrin under a different name as a medication to quit smoking. However, like most anti-depressants, the pills–whether they are called Wellbutrin or Zyban–can cause an increase in suicidal thoughts. Antidepressants have carried black box warnings about suicide risks since 2004.
Chantix: News about increased risk of suicide, violent behavior, and other mental health problems
From the approval of Chantix in May 2006 until July 2009, the drug was linked to reports of approximately 100 suicides, 200 suicide attempts, and almost 5,000 serious psychiatric events. Doctors are not required to report deaths or serious complications to the companies that make the medication or the FDA, although drug companies are required to do so. Because most doctors don’t report, it is assumed that the numbers are much higher and that those problems have continued since 2009. In fact, in May 2011, the Institute for Safe Medication Practices (ISMP) revealed that hundreds of cases of suicides, psychotic reactions, hostility, aggression and other serious problems tied to Chantix had not been properly reported to the FDA by Pfizer, the drug’s manufacturer. Among the 589 delayed reports of severe problems, there were more than 150 suicides-almost doubling those previously known. Thomas J. Moore, the ISMP senior scientist who analyzed the data, stated that, based on the FDA’s adverse event reports, Chantix is the riskiest of all drugs sold in the U.S. In the third quarter of 2010, it ranked first in reported deaths, with twice as many fatalities recorded as any other drug.
The discovered reports coincide with a study by Moore released in December 2010 examining all of the most serious adverse drug events reported to the FDA since 1968. Chantix had the largest number of reported cases of violence (408).
A large 2011 study found that Chantix was 8.4 times more likely to lead to suicide or self-injury compared to nicotine replacement products like nicotine gum or patches. There were 1,818 reported cases of suicidal thoughts or behavior for Chantix and only 50 for nicotine replacement products.
Increased risk of heart attack for patients with cardiovascular disease
Research has shown that these stop-smoking drugs affect not only mental health, but can also jeopardize physical health. In June 2011, the FDA warned that Chantix may be associated with an increased risk of certain cardiovascular adverse events in patients who have cardiovascular disease. After reviewing a randomized clinical trial of 700 smokers with stable cardiovascular disease, the FDA found that certain events, including heart attacks, were reported more frequently in patients treated with Chantix than in patients treated with placebo (2.0% vs. 0.9%).
Do the risks outweigh the benefits? NCHR says YES
Quitting smoking is usually a step towards improving one’s health, but doing so at the risk of mental or heart health is not a good compromise. Instead, there are other, safer ways to quit smoking.
The unreported deaths and serious injuries for people taking Chantix raises questions about whether other information is being withheld. Since most doctors don’t report adverse reactions to the FDA, it is likely that Chantix has caused many more deaths and injuries than reported. For that reason, we believe that Chantix is not a safe choice. At the very least, the mental health of anyone taking Chantix or Zyban should be closely monitored by a healthcare professional. Additionally, if you have a history of cardiovascular disease, consult your doctor before taking Chantix, and if you experience new or worsening symptoms of cardiovascular disease, contact your doctor immediately.
If you or someone you know is trying to quit smoking, be aware of the symptoms associated with quitting, and if symptoms develop, a healthcare professional should be consulted.
Controversy Over Black Box Warning
In 2014, the makers of Chantix lobbied the FDA to remove the black box warning on the drug, citing a meta-analysis, an observational study of hospital records, and reported adverse events to argue that dangerous side-effects were not as common as previously believed. However, we question the results of the meta-analysis, since many studies on Chantix were excluded.
Meta-analysis is a valuable tool, but its accuracy depends on the quality of each study and whether they fit together. The five studies included in the meta-analysis consisted of one study of schizophrenics, one study of depressed patients, and 3 studies of mentally healthy patients. It is important to study schizophrenics and depressed patients, but those data should not be analyzed together with 3 studies that exclude such patients.
To consider the implications of studies that claim to show that Chantix does not have serious psychiatric side effects, it is important to realize that most people with acute psychiatric side effect from medication do not end up in hospitals or the ER. Psychiatric side effects are often not reported in medical records. Because psychiatric commitment laws depend on acts of violence, not threats of violence, many people with dramatic psychiatric symptoms end up in jail, not in hospitals. In fact, some studies show that there are more mentally ill individuals in the criminal justice system than in psychiatric facilities.
Removal of Black Box Warning
After hearing the testimony about these shortcomings from NCHR President Diana Zuckerman and numerous other experts, the FDA decided to keep the black box warning on Chantix in 2015. However, in response to industry pressure, the FDA removed the black box in 2016, and the warnings that were in the black box are now part of the label under a heading of “Warnings and Precautions” for both Chantix and Zyban.[7, 8] Thus, although the official black box warning for Chantix has been removed, there are still warnings on their labels about the psychiatric risks of Chantix and Zyban. In addition to the label, which most patients do not read, the Medication Guide listed on the Chantix manufacturer’s website warns of the potential side effects of “New or worse mental health problems, such as changes in behavior or thinking, aggression, hostility, agitation, depressed mood, or suicidal thoughts or actions.” These warnings are also on the home page of Chantix.com. Zyban has a black box warning about suicidal thoughts, and warnings similar to Chantix on the label and medication guide.
Below are the current “Warnings and Precautions” listed for Chantix and Zyban:
Neuropsychiatric Adverse Events: Postmarketing reports of serious or clinically significant neuropsychiatric adverse events have included changes in mood (including depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, and panic, as well as suicidal ideation, suicide attempt, and completed suicide. Observe patients attempting to quit smoking with CHANTIX for the occurrence of such symptoms and instruct them to discontinue CHANTIX and contact a healthcare provider if they experience such adverse events.
Neuropsychiatric adverse events: Postmarketing reports of serious or clinically significant neuropsychiatric adverse events have included changes in mood (including depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, and panic, as well as suicidal ideation, suicide attempt, and completed suicide. Observe patients attempting to quit smoking with ZYBAN for the occurrence of such symptoms and instruct them to discontinue ZYBAN and contact a healthcare provider if they experience such adverse events
Below are the previous black box warnings for both Zyban and Chantix:
Serious neuropsychiatric reactions have occurred in patients taking ZYBAN for smoking cessation. The majority of these reactions occurred during bupropion treatment, but some occurred in the context of discontinuing treatment. In many cases, a causal relationship to bupropion treatment is not certain, because depressed mood may be a symptom of nicotine withdrawal. However, some of the cases occurred in patients taking ZYBAN who continued to smoke.
Some people have had changes in behavior, hostility, agitation, depressed mood, suicidal thoughts or actions while using CHANTIX to help them quit smoking. Some people had these symptoms when they began taking CHANTIX, and others developed them after several weeks of treatment or after stopping CHANTIX. If you, your family or caregiver notice agitation, hostility, depression or changes in behavior, thinking, or mood that are not typical for you, or you develop suicidal thoughts or actions, anxiety, panic, aggression, anger, mania, abnormal sensations, hallucinations, paranoia or confusion, stop taking CHANTIX and call your doctor right away. Also tell your doctor about any history of depression or other mental health problems before taking CHANTIX, as these symptoms may worsen while taking CHANTIX.
All articles on our website have been approved by Dr. Diana Zuckerman and other senior staff.
- Moore TJ, Glenmullen J, Furberg CD (2010) Prescription Drugs Associated with Reports of Violence Towards Others. PLoS ONE 5(12): e15337. Retrieved 27 May 2011 at http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0015337
- U.S. Food and Drug Administration. “Boxed Warning on Serious Mental Health Events to be Required for Chantix and Zyban.” Press release. FDA: Boxed Warning on Serious Mental Health Events to be Required for Chantix and Zyban. 1 July 2009.
- Xi ZX. Preclinical Pharmacology, Efficacy and Safety of Varenicline in Smoking Cessation and Clinical Utility in High Risk Patients. Drug, Healthcare and Patient Safety. 2010;2:39-48. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/21278851
- Moore TJ, Furberg CD, Glenmullen J, Maltsberger JT, Singh S. (2011) Suicidal behavior and depression in smoking cessation treatments. PLoS ONE 6: e27016.
- U.S. Food and Drug Administration. FDA Drug Safety Communication: Chantix (varenicline) may increase the risk of certain cardiovascular adverse events in patients with cardiovascular disease. 6 June 2011. Retrieved 6 July 2011 at http://www.fda.gov/Drugs/DrugSafety/ucm259161.htm
- FDA. FDA Drug Safety Communication: FDA revises description of mental health side effects of the stop-smoking medicines Chantix (varenicline) and Zyban (bupropion) to reflect clinical trial findings. FDA.gov. https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-revises-description-mental-health-side-effects-stop-smoking. December 16, 2016. Updated March 8, 2018.
- Chantix. [Package Insert]. New London, CT: PF PRISM CV; 2019. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021928s048lbl.pdf
- ZYBAN. [Package Insert]. Brentford, United Kingdom: GLAXOSMITHKLINE; 2019. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/020711s048lbl.pdf
- Chantix. [Medication Guide]. New York, NY: Pfizer; 2019. http://labeling.pfizer.com/ShowLabeling.aspx?id=557§ion=MedGuide