Bupropion (ZYBAN) for Smoking Cessation

For each individual attempt to quit smoking, the chances of success often may be very low, but they can be improved by looking for different kinds of help, including using smoking cessation drugs, and by making repeated attempts. The American Cancer Society (www.cancer.org) has a useful guide, “How to Quit Smoking or Smokeless Tobacco,” which discusses these issues.[1]

In 1997, the Food and Drug Administration (FDA) approved bupropion (ZYBAN) as a non-nicotine aid to smoking cessation. Bupropion is the same active ingredient found in the antidepressant drug WELLBUTRIN, which was first approved by the FDA in 1985. However, you do not have to be depressed to use bupropion as a smoking cessation aid.

If you are a smoker, quitting is the most important thing you can do for your health. The 2010 surgeon general’s report How Tobacco Smoke Causes Disease detailed how smoking damages practically every organ in the human body and found that smoking causes an overwhelming number of deadly diseases, from lung cancer and chronic obstructive pulmonary disease to heart attack and stroke.[2]

Public Citizen’s Health Research Group has designated Zyban as Limited Use because although it carries risks of serious adverse reactions, it does significantly increase the chances that smokers will successfully quit.

Smoking is an addiction

Quitting a smoking habit can be extremely challenging because it involves overcoming both a physical addiction and deeply ingrained psychological and social patterns.

Nicotine, a drug found naturally in tobacco, is very addictive. In fact, more people in the U.S. are addicted to nicotine than to any other drug.[3] Studies have shown that nicotine may be as addictive as heroin, cocaine and alcohol.[4] Symptoms of nicotine withdrawal include feeling irritable, angry or anxious; having trouble thinking; craving tobacco products; and feeling hungrier than usual.[5]

Zyban’s effectiveness

Multiple trials of bupropion have shown that the drug significantly increases the number of successful smoking cessation attempts, although the precise mechanism by which it works is unclear.

A 2014 study published in the Cochrane Database of Systematic Reviews (CDSR) analyzed the results of 44 randomized clinical trials that compared the effects of bupropion as an aid to smoking cessation with a placebo or non-drug treatment.[6] The trials together involved nearly 14,000 smokers and assessed abstinence from smoking at six or 12 months after enrollment in the trials. The study authors found that bupropion significantly increased the rate of long-term smoking cessation: Overall, bupropion-group subjects had an approximately 60 percent higher rate of achieving long-term abstinence from smoking than control-group subjects.

Adverse effects[7]

Seizures

Bupropion can cause seizures. The risk of seizures is dose-related, and doses over 300 milligrams (mg) per day for smoking cessation should not be used. The seizure rate associated with doses of sustained-release bupropion up to 300 mg per day in depressed patients is about 1 in 1,000 patients. The risk of seizures can be minimized by slowly increasing the dose up to a maximum of 300 mg.

The risk of seizures is also related to patient factors, clinical situations and other drugs taken concomitantly with bupropion, all of which must be considered when deciding whether to use this drug. Importantly, patients who have a seizure disorder; have been diagnosed with the eating disorders anorexia nervosa or bulimia; or are abruptly stopping use of alcohol, benzodiazepines (for example, diazepam [DIASTAT, VALIUM]) or seizure medications should never take bupropion because they are at significantly increased risk of seizures with use of the drug.

Other patient factors that may increase the risk of seizure with bupropion use include history of head trauma, brain tumors or infections, low blood sugar, low blood sodium level, low blood oxygen level, diabetes treated with insulin or oral drugs, and the presence of severe liver damage (cirrhosis).

Bupropion should be used with extreme caution in patients with severe liver cirrhosis. In these patients, a reduced frequency of dosing is required, as peak blood bupropion levels are substantially increased and higher-than-usual accumulation is likely to occur. The dose should not exceed 150 mg every other day in these patients.

Finally, concomitant use of other medications or substances that lower the seizure threshold — such as antipsychotics, tricyclic antidepressants, theophylline (ELIXOPHYLLIN, THEO-24, THEOCHRON), oral or injected glucocorticosteroids and cocaine, as well as excessive use of alcohol, sedatives (including benzodiazepines) and opioids — also increases the risk of seizures in bupropion users.

Use of bupropion should be discontinued and not restarted in patients who experience a seizure during treatment.

Neuropsychiatric effects

Patients treated with bupropion should be observed for abnormal psychiatric behaviors. The FDA-approved product labeling for Zyban and antidepressants that contain bupropion has a black-box warning about the risk of suicidal thoughts and behavior in children, adolescents and young adults (see box, below).

Other serious psychiatric adverse events reported in patients taking Zyban include changes in mood (mania and depression), psychosis, hallucinations, paranoia, delusions, homicidal thoughts, aggression, hostility, agitation, anxiety and panic. Most of these symptoms were reported in patients during treatment with bupropion, but some were also reported in patients after stopping bupropion.

Patients should stop taking ZYBAN and contact a health care professional immediately if agitation, depressed mood or changes in behavior or thinking that are not typical for the patient are observed, or if the patient develops suicidal ideation or suicidal behavior. In many postmarketing cases, resolution of symptoms after discontinuation of Zyban was reported. However, the symptoms persisted in some cases after the drug was stopped; therefore, ongoing monitoring and supportive care are needed until symptoms resolve.

What You Can Do

If you are trying to quit smoking, Zyban may be an appropriate treatment option to increase your chances of success. Use of any smoking cessation drug like Zyban or nicotine replacement therapy should be combined with a program of counseling. Smoking cessation drugs and counseling complement one another by addressing both the physiological and the sociopsychological aspects of the addiction.

You should not take Zyban if you have a seizure disorder; have been diagnosed with anorexia nervosa or bulimia; or are in the process of abruptly stopping use of alcohol, benzodiazepines or seizure medications.

Your family members and loved ones should monitor you closely for the aforementioned psychiatric symptoms and behaviors. You should stop taking Zyban and contact your doctor immediately if such abnormal behaviors or symptoms occur.

References

[1]American Cancer Society. How to quit smoking or smokeless tobacco. https://www.cancer.org/healthy/stay-away-from-tobacco/guide-quitting-smoking.html. Accessed June 15, 2018.

[2]U.S. Department of Health and Human Services. How Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for Smoking-Attributable Disease. A Report of the Surgeon General. 2010. http://whyquit.com/CDC/SGR_2010_How_Tobacco_Smoke_Causes_Disease.pdf. Accessed May 31, 2018.

[3]Centers for Disease Control and Prevention. Quitting smoking. December 11, 2017. https://www.cdc.gov/tobacco/data_statistics/fact_sheets/cessation/quitting/index.htm. Accessed May 31, 2018.

[4]Ibid.

[5]Ibid.

[6]Hughes JR, Stead LF, Hartmann-Boyce J, et al. Antidepressants for smoking cessation. Cochrane Database Syst Rev. 2014 Jan 8;(1):CD000031.

[7]GlaxoSmithKline. Label: bupropion (ZYBAN). May 2017. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020711s045s046s047lbl.pdf. Accessed May 31, 2018.