Smoking Cessation Aids

On May 28, 2002, The World Health Organization released startling statistics about the dangers of tobacco use and its prevalence on a global scale: one-third of the global male population smokes, every eight seconds someone dies from a tobacco-related illness, 10 million cigarettes are sold every minute worldwide and 12 times the number of citizens of the United Kingdom die of smoke than died fighting in World War II. More startling are the statistics for youth and tobacco use. In 1995 the Youth Risk Behavior Surveillance survey reported that 71 percent of American high school students had tried cigarettes and 35 percent of high school students continued to smoke. Encouraging news for American youth are reports that the most effective treatment for their cessation are their parents, however only if they are currently not smoking.

More than one in five deaths in the United States are caused each year by tobacco use making it the leading cause of premature death in the United States and environmental tobacco exposure (secondhand smoke) the fourth leading cause of preventable death. Secondhand or passive exposure effects are felt for generations as mothers pass along vulnerability to child in utero and early life. Health care professionals tout the treatment of tobacco smokers as some of their most difficult patients, not because of their unwillingness to get better, but because they often delay treatment or have repeated failures. Many give up and in a quit vs. benefit analysis deny that they have a reason to get better or that they are strong enough to proceed with treatment. Loved ones, health professionals and social messages need to motivate and then support these individuals in the decision to stop, and to stop now.

It is estimated that each year about 20 million people try to stop smoking. Of these 20 million “quitters,” only about 6 percent are ultimately successful. Health care professionals play a key role in the education of tobacco users who want to quit. Oftentimes health care professionals advise individuals to quit in times of medical necessity, although cessation has long-term health benefits regardless of the point in the smoker’s life. About 70 percent of smokers report that they want to quit smoking and have made several attempts at quitting. Helping smokers quit generally requires much more than a stern voice, medical directive or counseling.

Most smokers have tried to quit using no formal treatment. Going “cold-turkey” is not for everyone though; social prohibitions, trauma, medical advice and willpower have encouraged many short-lived quit attempts. Missing their smokes, depression, irritability and boredom are the most common reasons why smokers report they could not stick with it. Oftentimes the extra push comes from a pharmacological treatment, medication or alternative therapy. Relapse prevention can often be achieved with the addition of a pharmacologic agent to an existing therapy, such as behavioral modification. Common forms of pharmacological treatments include nicotine replacement, the use of antidepressants or Zyban®.       

Over-the counter nicotine-replacement therapies

At least 10 million smokers in the United States have used nicotine-replacement therapy most commonly in the form of nicotine gum or transdermal nicotine—“the patch.” Of nicotine-replacement therapy users, at least 8 million failed to stop smoking and many of these smokers are still seeking treatment. This failure rate for a detox-only treatment approach is not surprising since detox-only approaches for alcoholism fail as well. Many of these individuals trying to stop at home still have unused patches or gum. Nicotine transdermal patches and nicotine gum have been available for over-the-counter purchase since 1996. Manufacturers of over-the-counter therapies strove for effective treatments available at a price that made abstinence and successful cessation likely. Unfortunately, over-the-counter nicotine replacement remains more expensive than smoking cigarettes even with the recent addition of federal and state taxes on tobacco products.

Patches and gum combined with counseling are safe and effective possible treatments with abstinence rates of generally 10 percent to 20 percent reported at one year post therapy. A recent study comparing nicotine patches, gum, nasal spray and nicotine inhalers found each to be effective in helping patients with tobacco cessation; at the end of 12 weeks the abstinence rates were 20 percent to 24 percent for all four products. Unfortunately, nicotine-replacement by nasal spray or inhaler has a higher rate of noncompliance than the patch or gum. Side effects of the nasal spray included rhinitis, headache and even nosebleeds.

In another study, the dropout rate for the nasal spray was 25 percent due to troubling side effects. The inhaler had fewer side effects but due to comfort level and embarrassment most participants reported they would not continue to use the product. The nicotine inhaler provides as much nicotine as the gum and mimics the hand to-mouth-action associated with smoking. This may help alleviate some of the discomfort associated with the product but in practice, the inhaler is not more effective than any other nicotine-replacement method.

Relapse is always an issue with any addictive illness. Repeated treatment with nicotine-replacement therapy has not been found to be effective, although it has been the standard clinical practice to treat and re-treat until success is achieved. Most smokers take three to four attempts over a period of two to three years to eventually quit. Successful first-quit attempts could reduce tobacco exposure by at least six years, thereby reducing all the health problems caused by continued tobacco use. 

Non-nicotine treatments

Non-nicotine pharmacotherapy shown to be effective in tobacco cessation includes clonidine and antidepressants. Medications researched, but with lesser effectiveness include anti-anxiety medications and opioidblockers. Clonidine, an effective opioid withdrawal and alcohol abstinence medication, appears to alleviate nicotine withdrawal but not as well as nicotine replacement therapies. Adverse effects of clonidine include drowsiness, fatigue and dry mouth. 

Antidepressants

The antidepressant bupropion (Wellbutrin®) was thought to be effective because it had a similar effect in the brain as clonidine as well as having effects on the brain chemical dopamine. Previous studies with other antidepressants for smoking cessation included the use of doxepin (Sinequan®) and nortriptyline (Pamelor ®). Smokers who failed to quit were often those who report a personal history of depression, family history of depression or increase in depressive symptoms following cessation of smoking. Decreased depressive symptoms were associated with increased abstinence from tobacco products as well.  

Among the existing antidepressant treatments, Wellbutrin® (also known as Zyban®) has shown the most promise. Random assignment double-blind, placebo controlled studies have shown it to be safe and effective equal to the nicotine replacement systems currently in use for acute withdrawal. Zyban® appears far superior in relapse reduction. Its mechanism is unknown except that the noradrenergic effect appears to alleviate withdrawal symptoms. Side effects include insomnia and dry mouth. Both 150 mg and 300 mg dosages are effective, though 300 mg has shown to be more effective. Three hundred mg of Zyban® are better than nicotine-replacement therapy, with abstinence rates at one year being about 23 percent.

Unfortunately Zyban® has been shown to have little effect on craving but it has been shown to reduce feelings of illness, weight gain and boredom after smoking cessation. After repeated failures at cessation, people often are treated with Zyban® plus nicotine-replacement therapy. Combining non-nicotine medications with nicotine replacement appears to be more effective than using either alone. Zyban® has been used with the nicotine-replacement treatments and, while prospective double-blind studies failed to show superiority to Zyban® alone, the trend suggests that both treatments might be better for some patients.

Recent literature suggests that bupropion sustained release (SR) is the first-line non-nicotine medication. Bupropion SR doubles abstinence rates compared with placebo. It is also shown that bupropion has been successfully used in smoking cessation among difficult patients who are hard-core smokers such as those with cardiovascular disease, chronic obstructive pulmonary disease (COPD) and depression. Bupropion reduces withdrawal symptoms as well as weight gain and is effective for smoking cessation in people with and without a history of depression or alcoholism.

Anti-anxiety medications

Anti-anxiety medications, such as diazepam (Valium®) and beta-blockers, are not effective in smoking cessation. However, the most commonly tested anti-anxiety medication has been Buspar®. At present, there is not sufficient evidence to support the general usefulness of Buspar® as a smoking cessation aid.

Opioid blockers

Opioid blockers, especially naltrexone, have also been tried to aid tobacco cessation. Naltrexone blocks opioid receptors and has been used with great success in reducing alcohol relapse. Naltrexone may have similar but weaker effects on tobacco smoking cessation and at present has little promise with the exception of helping those who smoke and have alcoholism.

Caffeine

Individuals who smoke or who have smoked in the past are more likely to drink more caffeinated beverages and drinks that contain a higher concentration of caffeine, like coffee rather than tea. Recent research has shown that a relationship between caffeine and nicotine in the brain may lead to tobacco relapse and difficulty with cessation. A recent study looking at chronic caffeine and nicotine exposure in rats showed that caffeine did not affect plasma levels of nicotine and a nicotine metabolite. This suggests that caffeine may play a role in the development, persistence and relapse of smoking.

Finding what’s right for you

The first step toward smoking cessation is making the commitment to quit. Comparing the possible therapies can seem like an insurmountable task, but each has its own benefits. The most important thing is to find the therapy that you feel most comfortable with and that you are most likely to able to stick with for the long haul. Clearly the 12-year-old smoker who smokes for 25 years is different from the 30-year-old who starts smoking and continues for two years. Customizing a cessation program with the aid of a health care professional can lead to the most desirable outcome.

Pharmaceuticals cannot overcome the lack of motivation. They are useful and increase success rates in motivated quit attempts. They also can decrease weight gain and prevent depression. In general, Zyban® plus behavioral counseling and treating relapses again with Zyban® with counseling may be the best way to start. The use of Zyban® plus the patch or the gum may be an approach too. Others may be able to benefit from nicotine replacement, detoxification and relapse prevention. However, cost-benefit analysis, ease of administration and low adverse effects would be key in selecting the best pharmacological agent for each person. Someone might prefer adjusting his own dose and like to chew gum, while someone else may prefer the patch to do the work. Keep in mind that tobacco cessation, even in motivated individuals, may take more than one or two attempts. Also, no two treatments are alike and totally effective for all individuals. 

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World Health Organization, Fact Sheet: Smoking Statistics—May 28, 2002,

By Mark S. Gold, MD, and Barbara Lenz-Brunsman, MD
© 2001 University of Florida Brain Institute