Medications/Pharmacology

A Clinical Practice Guideline from the U.S. Public Health Service suggests that when feasible and not medically contraindicated, tobacco cessation interventions should include at least one Food and Drug Administration (FDA)-approved pharmaceutical aid (such as nicotine replacement therapy or medication) in combination with tobacco dependence counseling.^{1, 2}

Certain medications that do not contain nicotine have been found to be helpful at reducing the craving and withdrawal symptoms associated with smoking cessation. They are thought to help deal with the physical aspects of quitting smoking, while individuals work on breaking the mental habit of smoking.

These medications are available in prescription form only.

Types Of Anti-smoking Medications

• Varenicline Tartrate
• Bupropion

Click here for Medication Research Studies

 

Varenicline Tartrate (Chantix)

General Information

Varenicline Tartrate is a new molecular entity that received approval from the U.S. Food and Drug Administration in May 2006. It acts at the sites in the brain most affected by nicotine and helps users quit smoking in two ways: by providing some nicotine effects to ease withdrawal symptoms, and blocking the effects of nicotine from cigarettes if smoking is resumed. It is not nicotine, but it binds to the nicotine receptors in the brain, just as nicotine does.  Varenicline is not recommended for combination treatment with NRT due to its nicotine antagonist properties⁸.

Empirical Evidence on Effectivenes

According to a 2008 meta-analysis of 4 studies, it is estimated that 1mg daily of varenicline doubles a smoker's likelihood of long-term abstinence from tobacco compared to placebo.  Increasing the dose to 2mg daily approximately triples this abstinence likelihood⁸ .  Data presented at the 2005 meeting of the American Heart Association demonstrated varenicline tartrate to be more effective than bupoprion for smoking cessation over the course of a 12-week trial in two double-blind placebo controlled studies involving 2,000 smokers. In both studies, 44% quit by the end of the 12-week treatment period with varenicline tartrate, compared to 30% of those taking bupoprion. Researchers reported quitting response rates to be three times higher with varenicline tartrate than with placebo³ .  The researchers concluded that the significant reductions in craving and in some of the rewarding effects of smoking seen with 1mg of varenicline tartrate twice daily may assist in promoting abstinence and preventing relapse.

Figure derived from Chantix webpage.  Click here for more information.

Possible Side Effects

• Nausea
• Headache
• Vomiting
• Flatulence (gas)
• Insomnia
• Abnormal dreams
• Dysgeusia (change in taste perception)

Varenicline & Psychiatric Ilness

It is important to note that the clinical trials originally conducted for the approval of varenicline for smoking cessation did not include psychiatric patients.  Therefore, the effects of this medication on those with depression, bipolar disorder, and schizophrenia are not yet known.  According to the U.S. Department of Health and Human Services Clinical Practice Guideline 2008 Update⁷, two case reports cited exacerbations of psychiatric illness in patients who took varenicline.  In contrast, one recent smoking cessation study using varenicline did include smokers with mental illness and reported no evidence that varenicline worsened symptoms of depression, bipolar disorder, and/or psychosis⁸.  A warning issued by the FDA in February 2008 recommended that patients tell their health care providers about psychiatric illness history and that clinicians monitor patients for changes in mood and behavior while taking varenicline.⁹

Links for Brand Names

Chantix: http://www.chantix.com

• Recommended for 12-weeks, a second 12-week course can be helpful to maintain chances in the long term cessation.

 

Bupropion (Zyban)

General Information

Bupropion is an antidepressant believed to act upon norepinephrine and dopamine, two chemicals in the brain known to help regulate aspects of mood, cognition, and behavior. It has been used for the treatment of major depressive disorder, some anxiety disorders, and recently has been utilized as an aide for those attempting to quit smoking. It does not contain nicotine, but it does affect the chemicals in the brain associated with nicotine craving. It can be used in conjunction with other forms of nicotine replacement therapy.  The use of bupropion for smoking cessation is contraindicated in patients with seizure disorder, current or prior diagnoses of an eating disorder, use of monoamine oxidase (MAO) inhibitors within the past 14 days, or in patients taking other medications that contain bupropion⁸.

Empirical Evidence on Effectiveness

A meta-analytic review of twenty-four studies revealed that bupropion SR (sustained release) approximately doubles the likelihood of long-term abstinence (greater than 5 months) from tobacco use when compared to placebo treatment⁸.  Research has also demonstrated that bupropion SR tripled the quit rates among women and formerly depressed smokers.⁴ About 25 percent of the women who had taken bupropion SR were still abstaining from smoking a year later, triple the 8.5 percent success for those using a placebo tablet. The women on the placebo pill reported more negative mood than the men in that group, but no gender differences were observed for smokers using bupropion SR. A similar effect on abstinence rates was noted for smokers with a previous history of depression.⁴ Bupropion SR was also found to be effective for smoking cessation among African Americans and may be useful in reducing the health disparities associated with smoking.⁵ Researchers reviewed the evidence over the past decade on bupropion and noted its efficacy in alleviating craving to smoke.⁶

Possible Side Effects

• Dry mouth
• Nausea
• Insomnia
• Dizziness
• Weight loss
• Associated with risk of seizures, which is dose-related

Links to Brand Names

Zyban: http://us.gsk.com/products/assets/us_zyban.pdf

• Oral administration, 150 mg sustained release tablets

Wellbutrin: http://www.wellbutrin-xl.com

• Same ingredients as Zyban; often prescribed for mood management
• Once-daily, extended release tablet
• Available in 150 and 300 mg doses

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Medication Research Studies

Comparing varenicline and bupropion for craving, nicotine withdrawal symptoms, and rewarding effects of smoking

A study published in 2008 examined the effect of varenicline on craving and withdrawal symptoms.  Researchers compared varenicline to buproprion and placebo in two identical double-blind randomized trials.  Medication arms consisted of varenicline 1mg BID, bupropion SR (sustained release) 150 mg BID, and placebo.  Results indicated that varenicline reduced craving more than both bupropion and placebo, and that bupropion reduced craving more than placebo.  For participants who were abstinent from smoking, both varenicline and bupropion reduced negative affect more than placebo.  Interestingly, neither varenicline nor bupropion reduced symptoms of restlessness, insomnia, or appetite when compared with placebo.  The authors concluded that varenicline significantly reduced craving and reduced the rewarding effects of smoking, and that varenicline did so more effectively than bupropion.  The authors also speculated that the symptoms of insomnia, restlessness, and increased appetite may be related to receptors other than the specific alpha4-beta2 nicotinic acetylcholine receptor that varenicline targets.

West, R., Baker, C.L., Cappelleri, J.C., Bushmakin, A.G. (2008). Effect of varenicline and bupropion SR on craving, nicotine withdrawal symptoms, and rewarding effects of smoking during a quit attempt. Psychopharmacology, 197, 371-377.

Buproprion (Zyban) may be Particularly Effective for Women

Gender data suggests that buproprion may be particularly effective for women with regard to smoking cessation.  This study sought to examine whether the type of therapy administered with buproprion affected abstinence rates.  They examined 154 women age 30 or older who smoked at least 10 cigarettes/day.  Higher abstinence rates were observed for the group who received buproprion concurrently with Cognitive Behavioral Therapy (CBT) as compared with the group who received concurrent supportive therapy (ST).  However, findings provided only modest support for CBT as the preferred type of intensive therapy in conjunction with bupropion in women.

Schmitz, J.M., Stotts, A.L. (2007). Buproprion and cognitive-behavioral therapy for smoking cessation in women. Nicotine & Tobacco Research, 9 (7); 785.

To see more about this study, click here.

Long-term safety of Varenicline (Chantix) for Smoking Cessation

This randomized, double-blind, multi-center trial examined adult smokers, aged 18-75, who smoked an average of 10 ciagarettes/day or more.  They were randomly assigned to receive varenicline 1mg twice daily (n=251) or placebo (n=126) for 52 weeks.  The most common adverse events reported with varenicline in this trial included nausea (40.2%), abnormal dreams (22.7%), and insomnia (19.1%).  The researchers concluded that varenicline 1 mg BID can be safely administered for up to 1 year.  They also concluded that varenicline was a more effective smoking cessation aid than placebo throughout the study.

Williams, K.E., Reeves, K.R. et al. (2007). A double-blind study evaluating the long-term safety of varenicline for smoking cessation. Current Medical Research and Opinion, 23 (4); 793-801. 

To see more about this study, click here.

Use of Varenicline for an additional 12 weeks for Relapse Prevention

Using a double-blind research design, participants who quit smoking after 12 weeks of open-label varenicline treatment were given an additional 12 weeks of treatment.  During the intervention, participants randomly received either varenicline, 1 mg twice per day (n = 603) or placebo (n = 607) for an additional 12 weeks of treatment .  Smokers who achieved abstinence for at least 7 days at the end of 12 weeks of open-label varenicline treatment and were subsequently randomized to receive an additional 12 weeks of varenicline treatment showed significantly greater continuous abstinence in weeks 13 to 24 compared with placebo.  Increased abstinence for those taking varenicline continued beyond the 24 weeks of treatment to 52 weeks after treatment initiation.  Researchers concluded that varenicline may be an efficacious, safe, and well-tolerated agent for maintaining abstinence from smoking.

Tonstad, S., Tonnesen, P. et al. (2006). Effect of Maintence Therapy with Varenicline on Smoking Cessation: A Randcomized Controlled Trial. Journal of the American Medical Association, 296: 64-71. 

To see more about this study, click here.