Combine behavioral and nicotine replacement therapies to develop effective smoking cessation strategies.

When people quit smoking, they experience certain physical benefits such as improved circulation; lowered chances of developing cancers of the oral cavity, esophagus, lungs, larynx, pharynx, bladder, kidney, pancreas, and cervix (in women), and reduced chances of developing cardiovascular and cerebrovascular disease.1,2 Although these physical benefits sound wonderful, there are still many American smokers who cannot or will not achieve them. Why? In order to understand why it is so difficult to quit smoking, it may be useful to understand nicotine withdrawal, nicotine cravings, the available nicotine and non-nicotine replacement therapies (NRTs) and their efficacy rates, and the impact that behavioral therapies (BTs) can have on quitting.

Major deterrents to quitting smoking are the withdrawal symptoms of depressed mood, insomnia, irritability, anger, frustration, difficulty concentrating, restlessness, decreased heart rate, and increase in appetite or weight gain.3 These withdrawal symptoms can occur in an isolated fashion or concurrently. Unfortunately, these withdrawal symptoms are not minor in intensity. Rather they are incredibly strong. In fact, it is claimed that nicotine addiction is more severe than heroin or cocaine addiction.4

Nicotine cravings are also a strong deterrent to quitting. These cravings consist of an intense desire for nicotine and constant thoughts about smoking.1 Withdrawal symptoms and nicotine cravings can be overwhelming for those who wish to quit smoking. Considering the obstacles that withdrawal symptoms and cravings pose to quitting, what can help smokers become smoke-free? As evidenced by increased cessation rates, many believe that NRTs and non-NRTs are vital aids. When coupled with BTs, the quit rates become even more impressive.

The main goals of NRTs are to alleviate or minimize nicotine withdrawal symptoms and nicotine cravings. NRTs include a nicotine gum, nicotine patch, nicotine inhaler, and nicotine nasal spray. The most common non-NRT is administered in an oral tablet form. Research cites NRTs and non-NRTs as exhibiting only a small percentage of long-term success over placebo methods. However, more significant results are noted in research when BTs are coupled with NRTs and non-NRTs.

Nicotine Gum
Nicotine gum was the first FDA-approved NRT introduced into the consumer market. The gum works by delivering 2-4 mg of nicotine through buccal absorption following chewing. The nicotine in the gum is bound to an ion exchange resin that makes this absorption possible. Rose cites a 1995 study by Hughes on nicotine gum efficacy rates. Hughes found that the efficacy rates ranged from 1.4 to 2.7, with absolute quit rates ranging from 0 to 20%. This study also proposed that absolute quit rates seemed to be higher when behavioral therapy was included in the smoking cessation program. The rates for quitting at the 4-mg level appear to be greater for highly addicted smokers.5

Although nicotine gum is easily obtainable as an over-the-counter method and allows consumers to be active in fighting their addiction, it does have some drawbacks. Users of the gum have expressed displeasure with its taste. Difficulty complying with the chew and park method has also been noted.5 It has been reported that improperly chewed nicotine gum can result in nausea, gas, and an unpleasant burning sensation in the throat.2 The gum does not deliver a steady stream of nicotine. A sporadic supply of nicotine combined with difficulty following the park and chew method may be the factors responsible for client noncompliance.5

Nicotine Patch
The transdermal nicotine patch has become very popular in the consumer market. The patch is an over-the-counter NRT that works by delivering a controlled steady stream of nicotine through the skin at either a 21-mg/24-hour ratio or a 15-mg/16-hour ratio.5 In 1997, Richmond6 reported a review of studies that examined active patch efficacy at both the continuous and prolonged abstinence level. The efficacy rate of the patch was more than double those of placebo methods. However, it was also found that success rates greatly varied across studies. Rose5 cited Fiore et al as having found that both independent and intense counseling resulted in higher abstinence rates, with the intense counseling rates being higher.

Although the transdermal patch has low documentation of side effects other than mild skin irritation, excellent compliance rates, and effective rates of relieving withdrawal symptoms, it has some drawbacks as well. The initial decline in craving is small, although it increases with time.5 In addition, this NRT is passive. With this therapy alone, smokers do not personally become involved in fighting each craving and practicing the rituals that mimic smoking or some aspect of smoking.

Nicotine Inhaler
The nicotine inhaler is available by prescription and works by providing the client with a vaporized nicotine base to be inhaled. Each puff from the inhaler provides 13 µg of nicotine. Approximately 80-100 puffs over 20 minutes is considered to be roughly equal to 10 puffs from a cigarette smoked over 5 minutes.7 The nicotine is deposited primarily in the oral cavity and upper respiratory tract due to rapid diffusion.5,7 Although more long-term testing may be needed, preliminary reports suggest a significant success rate of 15% versus 5% placebo at 1 year.7 The greatest differences between inhaler efficacy rates and placebo efficacy rates were reported as occurring within the first 3 months and were based on an 80% confidence level, as opposed to the standard 90% confidence level. Relapse rates have been found to be both higher and lower than those in placebo groups.7

Despite the lack of conclusive evidence of long-term success, this therapy does allow clients to be active in their efforts to quit smoking and mimics the ritual hand-to-mouth actions and the physical taste and smell sensations of smoking. However, the large number of puffs needed to replace a sufficient amount of nicotine often results in underdosing.7 There are also side effects associated with the nicotine inhaler. These include gagging and lip and chest irritation when the user attempts to puff too deeply.7 These side effects were found to be less pervasive when the user puffs shallowly and rotates the lip placement of the inhaler. Schneider et al suggest that a higher success rate could be achieved by combining the inhaler with another NRT, namely the transdermal patch.7 However, a current information sheet provided by the pharmaceutical producer of the inhaler urges that the user not use any other nicotine-containing therapies.

Nicotine Nasal Spray
Nicotine nasal spray is also available only by prescription. This NRT works by delivering .05 mg of nicotine per squirt into the nostril where it is quickly absorbed into venous blood. One dose consists of a squirt into each nostril equating 1 mg of nicotine per dose.8 A 1995 study by Schneider et al found the nicotine nasal spray to have a 20% enhancement of early stage success rates while the drug was being actively used.8 The subjects in this study using the nicotine nasal spray showed significant success rates over the placebo subjects at all times up to and including 1 year. Two additional studies verify the clinical efficacy of the nicotine nasal spray over a placebo method. The results ranged from 1.8 to 2.6 times greater for the subjects who were actively using the nicotine nasal spray.9

To date, nicotine nasal spray provides the fastest nicotine delivery method on the market. It provides users with an active, immediate means of fighting cravings. The self-administered nature of the drug may, however, result in clients feeling “hooked” to the process of inhaling the nasal spray. As with any NRT, possible replacement dependence should be taken into consideration.8 Another side effect of this kind of therapy involves nose irritation that is generally mild and short-lived. When used in the presence of a cough due to flu or a cold, congestion or throat irritation may also occur.8

Nicotine Vapor
Nicotine vapor was introduced via prescription into the consumer market in 1998. The vapor inhaler is composed of a plastic mouthpiece housing a nicotine cartridge that contains a flavored 10-mg nicotine-loaded porous fitting.9 The vapor is inhaled through the tube into the mouth. The vapor is temperature sensitive, thus delivering a lower concentration of nicotine in colder temperatures. In controlled temperature settings, each inhalation contains approximately 13 µg of nicotine. Due to the low concentration, it takes approximately 70 inhalations to equal the amount of nicotine found in one piece of 2-mg nicotine gum.9 Three controlled studies9 have found significant results of 1.7-2.9 times greater abstinence rates for subjects using nicotine vapor relative to the placebo group. The long-term abstinence rates reported at 1 year are less clear and warrant further research.

Bupropion is a popular non-NRT that is administered in an oral tablet form. It is available by prescription only. Each tablet contains 150 mg of sustained-release bupropion. Interestingly, treatment with bupropion should begin while clients are still smoking but after they have defined a quit date, preferably during the second week of treatment.10 Initiation while the client is still smoking is recommended because it takes approximately 1 week to achieve sufficient levels of bupropion in the bloodstream. Treatment should start with 150 mg daily and increase after 3 days to the maximum recommended dose of 300 mg daily with no tapering dose required on conclusion of treatment.10

Originally developed as an antidepressant, bupropion is thought to work by affecting dopaminergic and noradrenergic activity and has been found to be effective in populations that were not suffering from depression. The influence of bupropion on the dopaminergic and noradrenergic activities results in lowered craving and withdrawal symptoms.10 The most common withdrawal symptoms that were most significantly alleviated include irritability, frustration, anger, anxiety, depressed mood, difficulty concentrating, and restlessness.10 In a study reported in 1999, Jorenby et al found that subjects treated with bupropion displayed higher long-term abstinence rates than subjects from the placebo group.11 This study also compared the efficacy of bupropion to the efficacy of the nicotine transdermal patch and a combination therapy of bupropion and the patch. Results revealed higher abstinence rates for the bupropion group than the nicotine transdermal patch group and the combination group. These abstinence rates were determined at both the conclusion of the study and in follow-up measurements.11

Although the success rates for bupropion are high, there are some side effects that need to be taken under consideration. Bupropion should not be used by people suffering from either anorexia or bulimia due to an increased risk of seizure.10 Two other side effects have been associated with bupropion—insomnia and dry mouth. It has been reported that averting a late night dosage can alleviate insomnia. Dry mouth was not severe, and both side effects were found to diminish with time.10

Other Non-NRTs
Other non-NRTs that are currently in use include clonidine, buspirone, and naltrexone. Clonidine is a relatively affordable prescription drug that was originally used to treat hypertension. It is an alpha2-noradrenegic agonist that has been found to reduce cravings and withdrawal symptoms.10 During short-term follow-ups, the majority of studies have reported significantly higher success rates for those using clonidine opposed to those using a placebo.10 It is noteworthy to mention that females tend to have more positive effects than males. The best success rates for clonidine are found when the drug treatment is coupled with a behavioral modification therapy. The known side effects of clonidine include fatigue, drowsiness, and dry mouth.10

Buspirone is a nonaddicting, nonsedating compound that first became available in the 1980s for the treatment of anxiety. It has been suggested that buspirone is an agonist for the serotinin 5-HT1A receptor, including lesser dopamine D2 receptor activity. Studies have shown that buspirone helps to alleviate withdrawal symptoms and minimize cravings.10 Side effects associated with the use of this prescription drug include: dizziness, nausea, headache, nervousness, and lightheadedness. Further research on buspirone as an effective non-NRT needs to be performed.

Naltrexone was originally given to people who are alcohol dependent. The effectiveness of this prescription drug has been credited to its ability to curb the antagonism of b-opiate receptors, thus reducing the activation of the mesolimbic dopamine system.12 According to preliminary reports, the reduced activation of the mesolimbic system acts to diminish nicotine cravings.

The most promising report of naltrexone found that this drug works best in conjunction with a NRT in reducing cravings after exposure to a smoking cue, reducing withdrawal symptoms, and reducing negative affect after a smoking cue was presented. However, further research needs to be performed before this drug becomes accepted and prescribed as a non-NRT.

Combination Therapies
Although each NRT and non-NRT has an average efficacy rate, the efficacy of an overall smoking cessation program becomes substantial when combination treatments are employed. Mary Bearman, M Psy, CHT, director of the Tobacco Cessation Program of Centura Health, Denver, agrees, “When people put several things together in terms of how they are going to quit, they are more successful.” Combination treatments consist of blending more than one NRT or non-NRT.

A 1993 study, which rated the efficacy of the patch and gum independently and in combination, found that the combination resulted in the participants rating the intensity of their withdrawal symptoms at the same level as if they were still smoking.9 Another study conducted in 1995 found that the combination of patch and gum therapies resulted in higher abstinent rates at week 24, although long-term abstinent rates seemed to be unaffected.9

Another promising combination of therapies involves the nicotine transdermal patch with a nonnicotine citric acid inhaler. The inhaler mimics the airway sensations of smoking a cigarette. At the end of a 10-week trial, subjects who used an active inhaler and nicotine transdermal patch had higher abstinent rates (19.5%) than subjects who used the nicotine transdermal patch and placebo inhaler (6.8%). However, poor long-term rates were noted.

Psychological Factors
Although combination therapies appear promising, the possibility of nicotine toxicity also needs to be evaluated. Nicotine toxicity results in illness when the nicotine levels in the bloodstream are too high.9 The threat of nicotine toxicity can be avoided if one of the therapies is a self-administered therapy such as nicotine gum, the nicotine inhaler, or nicotine nasal spray. Although initial studies on combination therapies appear promising in the short term, more long-term research studies need to be performed.

Despite the clinical requirements for dependence and regardless of the latest medical and psychological studies on the efficacy of nicotine and nonnicotine therapies, a very important factor of smoking needs to be addressed. Smoking is not only composed of a medical addiction; there is a psychological factor as well. The psychological process of learning to be a non-smoker is very difficult. In fact, quitting is so difficult that multiple attempts are often necessary before a smoker quits for good. According to Barbara Melin, director of advocacy for the American Cancer Society—Rocky Mountain Division, Denver, and author of When Someone You Care About Smokes, “It takes the average smoker 10-11 attempts to quit over 18 years before they stop smoking.”

Smokers also often mourn the ritual of smoking that had become engrained in their daily routine. Melin says of an average pack-a-day smoker that “combining behavioral therapy is so important because smoking is a conscious act that is performed 200-300 times a day. It takes 10-15 ‘hits’ off a cigarette to finish smoking it. Each ‘hit’ is considered a separate smoking act and repetition reinforces behavior. Behavior therapies teach smokers to anticipate emergency situations and learn different behaviors.” Newly learned behaviors could include turning irrational thoughts about smoking into rational thoughts about quitting and learning time management skills so that free time is not occupied by smoking or thoughts of smoking.4

Considering the high value that previous smokers place on advice from physicians,6 respiratory care practitioners can take advantage of an excellent opportunity to positively influence the health of their clients. They can help by becoming aware of the different NRTs and non-NRTs, their success rates and side effects, and the important impact that BTs can have for clients who wish to become smoke-free. There are approximately 46 million Americans who smoke. According to a 1993 report by the Centers for Disease Control and Prevention, every year approximately 34% of those 46 million try to quit smoking.5 Yet, only 2.5% are successful. However, the involvement of respiratory care practitioners may help increase the deeply disturbing low successful quit rate.

Jennifer Vavra is a contributing writer for RT Magazine.

1. Covey LS. Nicotine dependence and its associations with psychiatric disorders: research evidence and treatment implications. In: Seidman DF, Covey LS, eds. Helping the Hard-Core Smoker: A Clinician’s Guide. 1st ed. Mahwah, NJ: Lawrence Erlbaum Associates; 1999:23-51.
2. Boyd NR, Orleans CT. Intervening with older smokers. In: Seidman DF, Covey LS, eds. Helping the Hard-Core Smoker: A Clinician’s Guide. 1st ed. Mahwah, NJ: Lawrence Erlbaum Associates; 1999:115-136.
3. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: American Psychiatric Association; 1996:133-134.
4. Bates RC, Bueltel LM. Creating a comprehensive smoking cessation program. AARC Times. 1999;23:46-53.
5. Rose JE. Nicotine addiction and treatment. Annu Rev Med. 1996;47:493-507.
6. Richmond RL. A comparison of measures used to assess effectiveness of the transdermal nicotine patch at 1 year. Addict Behav. 1997;22:753-757.
7. Schneider NG, Olmstead R, Mody FV, et al. Efficacy of a nicotine inhaler in smoking cessation: a double-blind, placebo-controlled trial. Addiction. 1996;91:1293-1306.
8. Schneider NG, Olmstead R, Mody FV, et al. Efficacy of a nasal spray in smoking cessation: a placebo controlled, double-blind trial. Addiction. 1995;90:1671-1682.
9. Eissenberg T, Stitzer ML, Henningfield JE. Current issues in nicotine replacement. In: Seidman DF, Covey LS, eds. Helping the Hard-Core Smoker: A Clinician’s Guide. 1st ed. Mahwah, NJ: Lawrence Erlbaum Associates; 1999:137-158.
10. Johnston A, Robinson MD, Adams DP, et al. Nonnicotine medications for smoking cessation. In: Seidman DF, Covey LS, eds. Helping the Hard-Core Smoker: A Clinician’s Guide. 1st ed. Mahwah, NJ: Lawrence Erlbaum Associates; 1999:159-174.
11. Jorenby DE, Leischow SJ, Nides MA, et al. A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation. N Engl J Med. 1999;9:685-691.
12. Hutchinson KE, Monti PM, Rohsenow DJ, et al. Effects of naltrexone with nicotine replacement on smoking
cue reactivity; preliminary results. Psychopharmacology. 1999;142:139-142.