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Efficacy of nicotine chewing gum in facilitating smoking cessation
ARTICLES
Helping patients to quit smoking is in the interest of all health professionals, including dentists. This chewing gum may be able to help.
Efficacy of nicotine chewing gum in facilitating smoking cessation Arden G. Christen, DDS, MSD James L. M cDonald, Jr., PhD Byron L. Olson, PhD
Catherine A. Drook, LDH George K. Stookey, PhD
M
any d entists have observed that various tobacco products are associated w ith an array of oral and perioral condi tions in their patients. Some studies in d i cate that abrasion, altered taste and smell, c a n c e r, c a lc u lu s b u ild - u p , d e la y e d w o u n d h ea lin g , h airy to n g u e, leu k o plakia, periodontal disease, sinusitis, and stained teeth are im plicated w ith tobacco usage.1,2 In 1964, w ith publication of the US Surgeon G eneral’s Smoking and Health Report, all health professionals became aw are of th e serious th reat p o sed by sm oking to an in d iv id u a l’s p erso n al health.3 Since that initial publication, 14 su p p le m e n ta ry m ajor re p o rts on th e health consequences of sm oking have been published. In 1979, this m aterial was sum m arized and published in a work of more than 1,000 pages dealing w ith virtu a lly ev ery a sp e c t of sm o k in g an d health.4 In 1964, the House of Delegates of the A m erican Dental A ssociation resolved that “mem bers be encouraged to inform their patients of the health hazards of the use of tobacco and, especially w ith young people, w arn against acquiring the habit of cigarette sm oking.”5 Smoking is not 594 ■ JADA, Vol. 108, A pril 1984
perm itted during the scientific sessions of the A ssociation and during m any other activities sponsored by state and district dental societies. Since the early 1960s, an increasing num ber of Am erican dentists have quit smoking. A random sam ple of 630 Amer ican dentists (7.9% of the total) w ho at tended the first three days of the 124th ADA annual session show ed 52 dentists
(8.3%) who currently smoked and only 34 (5.4%) w ho smoked cigarettes.6 This is in contrast to results of the first nationw ide survey, conducted in 1967 that reported 34% of dentists sm oked,7 and a 1975 sur vey show ing that the smoking rate of den tists had dropped to 23%.8 T hree surveys, c o n d u cte d betw een 1967 and 1983, indicate that dentists in creasingly believe that they should be
A R T IC L E S
actively involved in efforts to help their patients and the general public to quit smoking.6"8 These studies indicate that this feeling of responsibility for helping others has grown stronger with time. The concept of helping patients to quit smok ing is consistent with one of the major overall thrusts of the dental profession since the late 1960s: disease prevention. Stop-smoking efforts have led to a de crease in the percentage of American males who smoke—53% in 1964 vs 37% today.9 However, 55 m illion Americans still smoke. The majority of smokers (90%) have tried to quit smoking or would probably quit, if only they could find an effective way to do so.4 Stop-smoking efforts have largely been directed at the psychologic dependence a sso cia ted w ith cig a rette sm o k in g . Nicotine dependence, the second major ele m en t in s m o k in g , h as b e e n a p proached only with proprietary products purporting to substitute for nicotine. Re cently, a nicotine-containing gum has be come available. Studies in Europe have shown significant increases in smoking quit-rates among patients treated with the gum.10-12 The gum, which contains 2 mg n ic o tin e per p ie c e , prod u ces b lood nicotine concentrations similar to, but less than, a single cigarette and relieves symptoms of nicotine withdrawal. Because smokers may adjust their in take of nicotine directly or indirectly via sensory clues obtained from taste or tar ir ritation, nicotine contents of different types of cigarettes are poor indicators of plasma nicotine concentrations in smok ers.13 Rather, the methods of smoking used and the intensity of smoking are more important factors in determining plasma nicotine concentrations. There fore, the statement that “the nicotinecontaining chewing gum produces blood levels of less than a single cigarette” is probably accurate for all cigarettes re gardless of nicotine content under most circumstances.14 This paper reports the results of a study designed to examine the efficacy of a nicotine-containing chew ing gum in helping subjects to stop cigarette smok ing; the study was done in a universitybased dental research facility.
Method Study design The study w as designed as a randomized, double-blind, parallel, placebo-controlled study of the efficacy of a nicotine-containing chewing gum (Nicorette) as determined by change in smoking behavior. After a pretest, no-gum control period, efficacy measures were performed at six and 15 weeks after the test and control gum was provided. Study candidates were recruited from the Indiana University campus and nearby com munity by posters and newspaper advertising.
Entry criteria included the fact that all partici pants were cigarette smokers desirous of quit ting and were provided written informed con sent forms. Those people who met the initial entry criteria had a thorough dental prophy laxis and were asked to maintain their normal dietary, oral hygiene, and smoking habits for the next eight weeks. After the eight-week pre test period, the subjects were examined clini cally and questionnaires were completed to as sess their usual dietary, oral hygiene, and smoking habits. A baseline, expired-breath carbon monoxide analysis (CO) was performed to verify smoking status. Carbon m onoxide levels were measured using a breath analyzer (Mini CO Carbon Monoxide Breath Analyzer) calibrated daily for the CO content using a calibration gas cyl inder having 60 ppm CO. Subjects were in structed to hold their breath for 20 seconds, then to discard the first portion of expired breath and collect the last portion in a sample balloon (the last portion is defined as alveolar air). The breath sa m p les w ere th en im m ediately analyzed. Participants w ith CO levels of < 8 ppm were considered nonsmok ers, whereas those with values of 8 or more were considered smokers.10,11 All test values were corrected for ambient CO. Subjects were stratified on the basis of stained dental pellicle and then randomly al located into either the nicotine or placebo gum group. Because of the known increase in pelli cle stain in smokers,13'1S the development of stain during the pretest period was considered an indication of the intensity of smoking and was used as a stratification parameter. Subjects were then given another dental prophylaxis, instructions for use of the gum, and were shown a brief program of instructions on how to stop smoking. The stop-smoking program consisted of: a self-test designed to help sub jects learn why they smoke; a short pamphlet that presented hints on smoking cessation; and a brief videotape that discussed use of the pamphlet. Subjects were show n the stopsmoking program either individually or in small groups. Two to three days after the gum was distrib uted, the subjects were contacted by telephone to ascertain whether problems with gum use had arisen and to answer questions. Through out the study, gum was distributed to subjects in a quantity believed to be sufficient until their next scheduled appointment. However, subjects were instructed to return to the dental clinic for additional supplies of gum if needed.
Patient selection i
A total of 208 subjects entered the study, all of whom were cigarette smokers who reported a desire to stop smoking. They were in good general health and met certain dental criteria (at least 20 natural teeth that included at least ten of 12 maxillary and mandibular anterior teeth present without crowns or large restora tions). Subjects were not accepted if they had rheumatic fever, heart disease, gastric ulcer, hepatitis, or were pregnant. Poor oral hygiene, destructive dental caries, and presence of den tal appliances (dentures, orthodontic bands) also excluded subjects. The 103 subjects in the placebo gum group and the 105 subjects in the nicotine gum group were similar in characteristics (Table 1). Mar ginally significant differences occurred in av-
Table 1 ■ Demographic data. Statistic No. of subjects Age (years) Gender: male female No. of cigarettes smoked per day No. of years smoked Baseline CO (PPM) Fagerstrom (Q) Score* >6 «6
Experimental group
Placebo group
105 33.2*
103 35.5
43 62
42 61
30.1
30.5
15.2+ 35.4
17.6 36.4
48 49
32 64
The Fagerstrom (Q) isderivedfroma smoking questionnaire and is used as a measure of smoking dependence. Scores greater than six are considered to be highly nicotine depen dent. The differences in Q scores between the two groups was marginally significant (P = .073) with more patients in the ex perimental group having a greater dependence on nicotine. *P = .061 tP = .051 ♦Fifteen subjects (eight and seven in the experimental and placebo groups, respectively) withdrew before completion of the pretest period and did not provide this information.
Table 2 ■ Subject accounting. Examination time
Experimental Placebo group group
Initial enrollment Six weeks Evaluable active patients Evaluable withdrawals Nonevaluable active patients Nonevaluable withdrawals Withdrawal rates 15 weeks Evaluable patients Withdrawals Withdrawal rates
105
103
90 1 2 12 12.4%
91 2 3 7 8.7%
78 27 25.7%
79 24 23.3%
erage age, the number of years of smoking, and in baseline Fagerstrom (Q) scores. Subjects w ho are highly dependent on nicotine may de rive more benefit from u se o f a nicotinecontaining gum than w ill subjects w hose nicotine dependence is lower. Fagerstrom de signed an eight-item questionnaire to test this s p e c u la tio n . S u b jects w ith a sc o re > 6 (maximum score = 11) were identified as highly dependent.12 At the baseline examina tion, it was found that the subjects in the nicotine-gum group were 2.3 years younger and had smoked for 2.4 fewer years than those in the placebo group. In addition, a greater number of subjects in the nicotine-gum group had a high dependence on nicotine. No other differences were observed between the groups w ith regard to other demographic, clinical, or psychologic characteristics.
Subject accounting Of the 208 subjects who entered the study, 181 were available for interview and examination at the six-week visit. At the four-month visit (15 weeks), 157 subjects were continuing to participate and were available for examina tion. Withdrawal rates for the nicotine and placebo gum groups at the six- and 15-week visits are presented in Table 2. The number of subjects w ithdraw ing from the study w as comparable in both the experim ental and placebo groups. During the pretest, at 6, and 15 weeks—these numbers were 8, 7, and 12 vs 7,
C h ris te n -O th e rs : EFFICACY O F N IC O TIN E C H EW IN G G U M ■ 595
A R T IC L E S
5, and 12 w ith the resultant total dropouts of 2 7 of 105 (25.7%) and 24 of 103 (23.3%) in the ex perim ental and placebo groups, respectively. Panelists w ho w ithdrew from th e study did so for personal reasons (loss of interest or incon veniences of examinations). None of the w ith draw als at either six or 15 weeks was the result of adverse effects of the gum.
Table 3 ■ Quit-rates at six and 15 weeks (num ber of patients and percent).____________________ Parameter Patients evaluated at six weeks Patients evaluated at 15 weeks
M edications T he exp erim en tal gum co n tained 2 mg of nicotine per piece of gum; th e placebo gum was identical in appearance an d as sim ilar as possible in taste to the experim ental gum but contained no nicotine. Both chewing gums w ere sugar-free. The nicotine w as contained in a sugar-free resin/gum matrix in the experi m ental gum. N icotine was released from the matrix by chew ing and was buccally absorbed, w ith the rate of release depending on the inten sity of chew ing. Gum was distributed on a double-blind basis. Gum usage was on an ad libitum basis, w ith a m axim um of 30 pieces per day allowed. Sub jects w ere instructed to carry the gum with them and to chew a piece of gum slowly w hen ever they felt a need to smoke. Titration of the n u m b e r of p ie c e s p e r d ay w as su b je c tdependent and was expected to vary w ith se verity of sm oking and w ith adverse effects. Subjects w ere instructed to decrease gum use gradually as their urge to smoke decreased. Even after they stopped using the gum, they w ere instructed to carry it w ith them for use should the urge to smoke return.
N
Experimental group
Placebo group
Significance probability
208
36/105 (34.3)
11/103 (10.7)
< .001
208
13/105 (12.4)
5/103
Treatment* Level of dependency High (Q > 6) Low (Q s 6)
Experimental
Placebo
Significance probability
45.8% (22/48)
9.4% (3/32)
.001
28.6% (14/49)
12.5% (8/64)
.027
*Data w ere n o t a v a ila b le o n se v en p lac e b o a n d e ig h t e x p e rim e n ta l p atien ts.
Table 5 ■ Change in average daily num ber of cigarettes s m o k e d a fte r 15 w e e k s.*
Smoking quit-rates for th e experim ental and placebo groups at six and 15 weeks are pre sented in Tables 3 and 4. Calculations were m ade by using all patients w ho entered the study. Thus, even those w ho discontinued or were lost to follow-up were used and were con sidered as failures although som e of these may have q u it sm oking. These calculations are therefore more conservative as these patients are included. Significant differences in quitrates betw een patients provided the experi m e n ta l n ic o tin e -c o n ta in in g gum a n d th e placebo gum occurred at both six and 15 weeks (Table 3). However, the total population avail able for evaluation and those rem aining absti nent decreased during this tim e. For example, 596 ■ I ADA, Vol. 108. ADril 1984
Significance probability
Statistic
Experimental
Placebo
Mean change (SD) Sam ple size
-1 1 .1 (11.4) 73
-1 4 .6 (12.2) 57
.091
* O n ly c o n tin u o u s sm okers are in c lu d e d . C h an g e w as d e fin e d a s th e d ifferen ce b e tw e en av erag e d a ily n u m b er of cig arettes sm o k e d at stu d y e n d v s t h e p re stu d y b a se lin e v alu e.
Table 6 ■ Daily average num ber of pieces chew ed. Six weeks
Efficacy
.046
Table 4 ■ Quit-rates at six weeks according to level of nicotine dependency.
E valuations Evaluations of the efficacy of the experimental vs placebo gum were based on self-reports of smoking cessation (by questionnaire) and con firmatory breath CO determ inations. A suc cessful quitter was defined by a self-report of abstinence and an expired breath CO value of less than 8 ppm . These evaluations were per formed six and 15 weeks after providing the gum . T he types and frequency of adverse events w ere also evaluated at these times. Group com parisons w ere m ade w ith twosid e d , tw o -sam p le t-te sts for q u an titativ e characteristics and w ith tw o-sided x2 tests for qualitative data. The single degree-of-freedom X 2 tests w ere im plem ented w ith continuity cor rection. Moreover, such tests involving absti nence rates w ere conducted as one-sided pro cedures.
(4.8)
Statistic Mean (SD) Sample size
15 weeks
Experimental
Placebo
E xperim ental
Placebo
7.6 (5.1) 62
6.7 (5.9) 69
2.8 (4.6) 27
1.8 (3.1) 34
the num ber of abstinent patients in the exper im ental group was 36 at six weeks and only 13 at 15 weeks; the decline in the num ber of suc cessful abstainers was the result of the resum p tion of smoking by 11 panelists and the w ith drawal of 12 patients from the study. Stratifying the subjects who quit smoking on the basis of Q scores (Table 4) supports the concept that heavily nicotine-dependent sub jects w ill derive more benefit from a nicotinecontaining chewing gum than will less depen dent subjects (46% vs 29%). However, even the patients in the less dependent nicotine-gum group w ere more successful in discontinuing smoking than were those in the placebo group. Among those smokers who had decreased their rate of smoking, but had not quit, no real dif ference betw een the experim ental and placebo groups was seen (Table 5). Gum usage A lthough it appears that gum usage should continue for three to four months, the study in dicated that patients down-titrated themselves (Table 6). For example, patients averaged ap proxim ately seven pieces of gum per day dur
ing the first six weeks, but were using only two to three pieces per day by the 15th week. At the stu d y end, subjective evaluation of the gum was m ade by having the study partici pants answ er three questions dealing w ith palatability, oral sensation, and helpfulness. Generally, comparable proportions of subjects found the active and placebo gums to be likable (52% and 55%, respectively), and to produce about the sam e oral discomfort (37% and 23%, respectively). However, 65% of the users of the nicotine gum , in contrast to 33% for placebo, reported the gum to be effective in helping people to overcom e smoking. S afety Table 7 lists the m ost frequently reported ad verse effects by treatm ent at two, six, and 15 weeks after gum distribution. Adverse effects w ere tabulated by the num ber of complaints received, not by the num ber of subjects report ing. The adverse events that may be attributa ble to use of the nicotine-containing gum are nausea, eructation (belching), hiccups, and jaw m uscle ache. On the basis of telephone conversations w ith the patients w ho w ithdrew
A R T IC L E S
Table 7 ■ Frequency of reported adverse effects by time and treatment condition.*______ Experimental (wk) Placebo (wk) Adverse effect
2
6
15
2
6
15
Traumatic ulcer Jaw muscle ache Nausea Hiccups GI symptoms Eructation Aphthous ulcer
21 11 13 10 8 6 5
10 7 8 6 2 1 3
32 17 18 15 11 7 6
20 5 1 0 5 1 5
11 4 3 0 1 0 2
26 10 4 0 7 1 7
‘Multiple other adverse effects were reported once or twice during the 15 weeks; such effects included cheek biting, tingl ing tongue, headache, anorexia, irritability, and tinnitus.
from the study, it was determined that none of the subjects withdrew as the result of adverse effects of gum usage.
Discussion The major fu n ction of a n ic o tin econtaining chewing gum in smoking ces sation is to alleviate the symptoms of nicotine dependence, allow ing the smoker to concentrate his or her efforts on the psychologic aspects of smoking cessa tion. The initial taste experience with the nicotine gum is aversive (few smokers like the taste initially, but grow accus tomed to it with use). Blood levels achieved by the 2-mg gum are approxi mately half that obtained with a cigarette. This may imply that the primary effect of the gum is to alleviate withdrawal rather than to produce the positive stimulatory effects of smoking cigarettes.14,15 Con sequently, smokers must be highly moti vated to quit and must be willing to con tinue gum use for at least three months. Indeed, whereas the optimal duration of use is unclear, it has been suggested that three to four months of abstinence are re quired for the strength of the habit to abate sufficiently to increase the likeli hood of success.10 In this study, patients used an average of eight pieces of the nicotine gum/day for six weeks, resulting in a quit-rate three times greater than that observed in the placebo group (34% vs 11%). However, the degree of success is less than has been reported in other studies that use behav ior modification techniques. This is prob ably the result of the minimal amount of psych ologic support the patients re ceived, being exposed to the program only at the initial visit with a reinforce ment session at two weeks. As a result, the greatest success (46%) occurred in those patients with the highest nicotine depen dent component (Q > 6). Those patients in whom the physiologic component was less intense were less successful, but still achieved a 29% quit-rate. By 15 weeks, average gum consumption had declined to approximately three pieces/day, which
is below the level of usage usually rec ommended for optimal effects. This de creased usage may reflect a lack of moti vation on the part of the subject combined with the absence of a strong maintenance component in the program. This is sup ported by the 25% dropout rate at 15 weeks. It is clear that a chewing gum contain ing nicotine is an effective adjunct to a smoking cessation program. Its use in more intensive behavioral modification p rogram s p r o d u c e d q u it-r a te s a p proximating 60% at one month, com pared with 35% for the control group.10 The difference between these latter re sults and those observed in this investiga tion suggests the need for a greater re sponsibility of the professional personnel to support the patient throughout the withdrawal period. Constant encourage ment to withdraw from smoking and to continue using the gum for at least three to four months may be expected to en hance the final results. However, from this investigation it appears that even minimal support may be effective if the nicotine gum is used by highly motivated patients.
Conclusions The results of this study suggest the po tential benefits of a nicotine-containing chewing gum in aiding smoking cessa tion efforts. After six weeks of gum usage, 36 of 105 patients (34.3%) provided the experimental chewing gum had stopped smoking as compared with only 11 of the 103 p a tie n ts (10.7% ) p r o v id ed the placebo formulation. At the end of the 15-week study the number of patients who had successfully stopped smoking throughout the test period declined ap preciably in both the experimental and placebo groups; the corresponding values were 13 of 105 patients (12.4%) vs 5 of 103 (4.8%), respectively. Nevertheless, the in tergroup differences in quit-rates were statistically significant throughout the study period. At six weeks, subjects with high nicotine dependence were consid ered separately from those w ith low nicotine dependence. A noticeable esca lation of the success rate in the high nicotine dependent group attests to the particularly beneficial role of the nicotine gum in recalcitrant smokers. The increase in quit-rates using the nicotine gum was achieved with few adverse effects that were easily tolerated in conjunction with a minimal impersonal stop-smoking ces sation program.
_________________________________________ J W O A This research was supported by Merrell Dow Pharmaceuticals, Inc, Cincinnati.
The authors thank Mr. Stephen A. Miller, MS, Mer rell Dow Pharmaceuticals, Inc, for assistance in the conduct of this study, and to Dr. Ben J. Cerimele, Mer rell Dow Pharmaceuticals, Inc, for the statistical analysis of the data. Dr. Christen is associate professor and chairman, department of preventive dentistry; Dr. McDonald is professor, department of preventive dentistry; Dr. Olson is associate professor, department of preven tive dentistry; Ms. Drook is director, clinical pro grams, Oral Health Research Institute; Dr. Stookey is professor, department of preventive dentistry, and di rector, Oral Health Research Institute, Indiana Uni versity School of Dentistry. Address requests for re prints to Dr. Christen, Oral Health Research Institute, 415 Lansing St, Indianapolis, 46202.
1. Christen, A.G. The clinical effects of tobacco on oral tissue. JADA 81(6):1378-1382,1970. 2. Bastiaan, R.J., and Reade, P.C. The effects of to bacco smoking on oral and dental tissues. Austr Dent J 21:308-315,1976. 3. US Surgeon General’s Advisory Committee on Smoking and Health. Smoking and health: report of the committee. Pub No. 1103. Washington, DC, US Government Printing Office, 1964. 4. US Public Health Service. Smoking and health: a report of the surgeon general. Jan 11,1979. US De partment of Health, Education, and Welfare, Wash ington, DC, DHEW Pub no (PHS) 79-50066. 5. American Dental Association. News of den tistry. JADA 69:776, 1964. 6. Christen, A.G. Survey of smoking behavior and attitudes of 630 American dentists attending the 1983 ADA Annual Session. JADA, to be published. 7. Noll, C.E. Health professionals and the problems of smoking and health. Report 2. Dentist’s behavior, beliefs and attitudes toward smoking and health. Na tional Opinion Research Center, NORC Survey 4001, Chicago, University of Chicago, 1969. 8. N ational C learinghouse for Sm oking and Health. Survey of health professionals: smoking and health, 1975. US Department of Health, Education, and Welfare, Public Health Service, Center for Dis ease Control, Bureau of Health Education, 1976. 9. Fagerstrom, K.O. A comparison of psychologi cal and pharmacological treatment in smoking cessa tion. J Behav Med 5:343-351,1982. 10. Jarvis, M.J., and others. Randomised controlled trial of nicotine chewing gum. Br Med J 285:537-540, 1982. 11. Raw, M„ and others. Comparison of nicotine chewing gum and psychological treatments for de pendent smokers. Br Med J 281:481-482,1980. 12. Fagerstrom, K.O. Measuring degree of physical dependence to tobacco smoking with reference to in dividualization of treatment. Addict Behav 3:235241,1978. 13. Hill, P.; Haley, N.J.; and Wynder, E.L. Cigarette smoking: carboxyhem oglobin, plasm a nicotine, cotinine and thiocyanate vs. self-reported smoking data and cardiovascular disease. J Chronic Dis 36:439-449, 1983. 14. McNabb, M.E.; Ebert, R.V.; and McCusker, K. Plasma nicotine levels produced by chewing nicotine gum. JAMA 248:865-868,1982. 15. Ness, L.; Rosenkrans, D.L.; and Welford, J.F. An epidemiological study of factors affecting extrinsic staining of teeth in an English population. Commu nity Dent Oral Epidemiol 5:55-60,1977. 16. Addy, M., and others. Chlorhexidine staining: a clinical cross-over study and dietary analysis in volunteer subjects. J Dent Res 58{Spec Issue C):12-54, 1979. 17. Prayitno, S., and others. An in vivo study of dietary factors in the aetiology of tooth staining as sociated with the use of chlorhexidine. J Periodont Res 14:411-417,1979. a 18. Russell, M.A.; Raw, M.; and Jarvis, M.J. C lin i^ fl use of nicotine chewing gum. Br Med J 280:1!^H 1602,1980.
: EFFICACY OF NICOTINE CHEWING Gl
Helping patients to quit smoking is in the interest of all health professionals, including dentists. This chewing gum may be able to help.
Efficacy of nicotine chewing gum in facilitating smoking cessation Arden G. Christen, DDS, MSD James L. M cDonald, Jr., PhD Byron L. Olson, PhD
Catherine A. Drook, LDH George K. Stookey, PhD
M
any d entists have observed that various tobacco products are associated w ith an array of oral and perioral condi tions in their patients. Some studies in d i cate that abrasion, altered taste and smell, c a n c e r, c a lc u lu s b u ild - u p , d e la y e d w o u n d h ea lin g , h airy to n g u e, leu k o plakia, periodontal disease, sinusitis, and stained teeth are im plicated w ith tobacco usage.1,2 In 1964, w ith publication of the US Surgeon G eneral’s Smoking and Health Report, all health professionals became aw are of th e serious th reat p o sed by sm oking to an in d iv id u a l’s p erso n al health.3 Since that initial publication, 14 su p p le m e n ta ry m ajor re p o rts on th e health consequences of sm oking have been published. In 1979, this m aterial was sum m arized and published in a work of more than 1,000 pages dealing w ith virtu a lly ev ery a sp e c t of sm o k in g an d health.4 In 1964, the House of Delegates of the A m erican Dental A ssociation resolved that “mem bers be encouraged to inform their patients of the health hazards of the use of tobacco and, especially w ith young people, w arn against acquiring the habit of cigarette sm oking.”5 Smoking is not 594 ■ JADA, Vol. 108, A pril 1984
perm itted during the scientific sessions of the A ssociation and during m any other activities sponsored by state and district dental societies. Since the early 1960s, an increasing num ber of Am erican dentists have quit smoking. A random sam ple of 630 Amer ican dentists (7.9% of the total) w ho at tended the first three days of the 124th ADA annual session show ed 52 dentists
(8.3%) who currently smoked and only 34 (5.4%) w ho smoked cigarettes.6 This is in contrast to results of the first nationw ide survey, conducted in 1967 that reported 34% of dentists sm oked,7 and a 1975 sur vey show ing that the smoking rate of den tists had dropped to 23%.8 T hree surveys, c o n d u cte d betw een 1967 and 1983, indicate that dentists in creasingly believe that they should be
A R T IC L E S
actively involved in efforts to help their patients and the general public to quit smoking.6"8 These studies indicate that this feeling of responsibility for helping others has grown stronger with time. The concept of helping patients to quit smok ing is consistent with one of the major overall thrusts of the dental profession since the late 1960s: disease prevention. Stop-smoking efforts have led to a de crease in the percentage of American males who smoke—53% in 1964 vs 37% today.9 However, 55 m illion Americans still smoke. The majority of smokers (90%) have tried to quit smoking or would probably quit, if only they could find an effective way to do so.4 Stop-smoking efforts have largely been directed at the psychologic dependence a sso cia ted w ith cig a rette sm o k in g . Nicotine dependence, the second major ele m en t in s m o k in g , h as b e e n a p proached only with proprietary products purporting to substitute for nicotine. Re cently, a nicotine-containing gum has be come available. Studies in Europe have shown significant increases in smoking quit-rates among patients treated with the gum.10-12 The gum, which contains 2 mg n ic o tin e per p ie c e , prod u ces b lood nicotine concentrations similar to, but less than, a single cigarette and relieves symptoms of nicotine withdrawal. Because smokers may adjust their in take of nicotine directly or indirectly via sensory clues obtained from taste or tar ir ritation, nicotine contents of different types of cigarettes are poor indicators of plasma nicotine concentrations in smok ers.13 Rather, the methods of smoking used and the intensity of smoking are more important factors in determining plasma nicotine concentrations. There fore, the statement that “the nicotinecontaining chewing gum produces blood levels of less than a single cigarette” is probably accurate for all cigarettes re gardless of nicotine content under most circumstances.14 This paper reports the results of a study designed to examine the efficacy of a nicotine-containing chew ing gum in helping subjects to stop cigarette smok ing; the study was done in a universitybased dental research facility.
Method Study design The study w as designed as a randomized, double-blind, parallel, placebo-controlled study of the efficacy of a nicotine-containing chewing gum (Nicorette) as determined by change in smoking behavior. After a pretest, no-gum control period, efficacy measures were performed at six and 15 weeks after the test and control gum was provided. Study candidates were recruited from the Indiana University campus and nearby com munity by posters and newspaper advertising.
Entry criteria included the fact that all partici pants were cigarette smokers desirous of quit ting and were provided written informed con sent forms. Those people who met the initial entry criteria had a thorough dental prophy laxis and were asked to maintain their normal dietary, oral hygiene, and smoking habits for the next eight weeks. After the eight-week pre test period, the subjects were examined clini cally and questionnaires were completed to as sess their usual dietary, oral hygiene, and smoking habits. A baseline, expired-breath carbon monoxide analysis (CO) was performed to verify smoking status. Carbon m onoxide levels were measured using a breath analyzer (Mini CO Carbon Monoxide Breath Analyzer) calibrated daily for the CO content using a calibration gas cyl inder having 60 ppm CO. Subjects were in structed to hold their breath for 20 seconds, then to discard the first portion of expired breath and collect the last portion in a sample balloon (the last portion is defined as alveolar air). The breath sa m p les w ere th en im m ediately analyzed. Participants w ith CO levels of < 8 ppm were considered nonsmok ers, whereas those with values of 8 or more were considered smokers.10,11 All test values were corrected for ambient CO. Subjects were stratified on the basis of stained dental pellicle and then randomly al located into either the nicotine or placebo gum group. Because of the known increase in pelli cle stain in smokers,13'1S the development of stain during the pretest period was considered an indication of the intensity of smoking and was used as a stratification parameter. Subjects were then given another dental prophylaxis, instructions for use of the gum, and were shown a brief program of instructions on how to stop smoking. The stop-smoking program consisted of: a self-test designed to help sub jects learn why they smoke; a short pamphlet that presented hints on smoking cessation; and a brief videotape that discussed use of the pamphlet. Subjects were show n the stopsmoking program either individually or in small groups. Two to three days after the gum was distrib uted, the subjects were contacted by telephone to ascertain whether problems with gum use had arisen and to answer questions. Through out the study, gum was distributed to subjects in a quantity believed to be sufficient until their next scheduled appointment. However, subjects were instructed to return to the dental clinic for additional supplies of gum if needed.
Patient selection i
A total of 208 subjects entered the study, all of whom were cigarette smokers who reported a desire to stop smoking. They were in good general health and met certain dental criteria (at least 20 natural teeth that included at least ten of 12 maxillary and mandibular anterior teeth present without crowns or large restora tions). Subjects were not accepted if they had rheumatic fever, heart disease, gastric ulcer, hepatitis, or were pregnant. Poor oral hygiene, destructive dental caries, and presence of den tal appliances (dentures, orthodontic bands) also excluded subjects. The 103 subjects in the placebo gum group and the 105 subjects in the nicotine gum group were similar in characteristics (Table 1). Mar ginally significant differences occurred in av-
Table 1 ■ Demographic data. Statistic No. of subjects Age (years) Gender: male female No. of cigarettes smoked per day No. of years smoked Baseline CO (PPM) Fagerstrom (Q) Score* >6 «6
Experimental group
Placebo group
105 33.2*
103 35.5
43 62
42 61
30.1
30.5
15.2+ 35.4
17.6 36.4
48 49
32 64
The Fagerstrom (Q) isderivedfroma smoking questionnaire and is used as a measure of smoking dependence. Scores greater than six are considered to be highly nicotine depen dent. The differences in Q scores between the two groups was marginally significant (P = .073) with more patients in the ex perimental group having a greater dependence on nicotine. *P = .061 tP = .051 ♦Fifteen subjects (eight and seven in the experimental and placebo groups, respectively) withdrew before completion of the pretest period and did not provide this information.
Table 2 ■ Subject accounting. Examination time
Experimental Placebo group group
Initial enrollment Six weeks Evaluable active patients Evaluable withdrawals Nonevaluable active patients Nonevaluable withdrawals Withdrawal rates 15 weeks Evaluable patients Withdrawals Withdrawal rates
105
103
90 1 2 12 12.4%
91 2 3 7 8.7%
78 27 25.7%
79 24 23.3%
erage age, the number of years of smoking, and in baseline Fagerstrom (Q) scores. Subjects w ho are highly dependent on nicotine may de rive more benefit from u se o f a nicotinecontaining gum than w ill subjects w hose nicotine dependence is lower. Fagerstrom de signed an eight-item questionnaire to test this s p e c u la tio n . S u b jects w ith a sc o re > 6 (maximum score = 11) were identified as highly dependent.12 At the baseline examina tion, it was found that the subjects in the nicotine-gum group were 2.3 years younger and had smoked for 2.4 fewer years than those in the placebo group. In addition, a greater number of subjects in the nicotine-gum group had a high dependence on nicotine. No other differences were observed between the groups w ith regard to other demographic, clinical, or psychologic characteristics.
Subject accounting Of the 208 subjects who entered the study, 181 were available for interview and examination at the six-week visit. At the four-month visit (15 weeks), 157 subjects were continuing to participate and were available for examina tion. Withdrawal rates for the nicotine and placebo gum groups at the six- and 15-week visits are presented in Table 2. The number of subjects w ithdraw ing from the study w as comparable in both the experim ental and placebo groups. During the pretest, at 6, and 15 weeks—these numbers were 8, 7, and 12 vs 7,
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A R T IC L E S
5, and 12 w ith the resultant total dropouts of 2 7 of 105 (25.7%) and 24 of 103 (23.3%) in the ex perim ental and placebo groups, respectively. Panelists w ho w ithdrew from th e study did so for personal reasons (loss of interest or incon veniences of examinations). None of the w ith draw als at either six or 15 weeks was the result of adverse effects of the gum.
Table 3 ■ Quit-rates at six and 15 weeks (num ber of patients and percent).____________________ Parameter Patients evaluated at six weeks Patients evaluated at 15 weeks
M edications T he exp erim en tal gum co n tained 2 mg of nicotine per piece of gum; th e placebo gum was identical in appearance an d as sim ilar as possible in taste to the experim ental gum but contained no nicotine. Both chewing gums w ere sugar-free. The nicotine w as contained in a sugar-free resin/gum matrix in the experi m ental gum. N icotine was released from the matrix by chew ing and was buccally absorbed, w ith the rate of release depending on the inten sity of chew ing. Gum was distributed on a double-blind basis. Gum usage was on an ad libitum basis, w ith a m axim um of 30 pieces per day allowed. Sub jects w ere instructed to carry the gum with them and to chew a piece of gum slowly w hen ever they felt a need to smoke. Titration of the n u m b e r of p ie c e s p e r d ay w as su b je c tdependent and was expected to vary w ith se verity of sm oking and w ith adverse effects. Subjects w ere instructed to decrease gum use gradually as their urge to smoke decreased. Even after they stopped using the gum, they w ere instructed to carry it w ith them for use should the urge to smoke return.
N
Experimental group
Placebo group
Significance probability
208
36/105 (34.3)
11/103 (10.7)
< .001
208
13/105 (12.4)
5/103
Treatment* Level of dependency High (Q > 6) Low (Q s 6)
Experimental
Placebo
Significance probability
45.8% (22/48)
9.4% (3/32)
.001
28.6% (14/49)
12.5% (8/64)
.027
*Data w ere n o t a v a ila b le o n se v en p lac e b o a n d e ig h t e x p e rim e n ta l p atien ts.
Table 5 ■ Change in average daily num ber of cigarettes s m o k e d a fte r 15 w e e k s.*
Smoking quit-rates for th e experim ental and placebo groups at six and 15 weeks are pre sented in Tables 3 and 4. Calculations were m ade by using all patients w ho entered the study. Thus, even those w ho discontinued or were lost to follow-up were used and were con sidered as failures although som e of these may have q u it sm oking. These calculations are therefore more conservative as these patients are included. Significant differences in quitrates betw een patients provided the experi m e n ta l n ic o tin e -c o n ta in in g gum a n d th e placebo gum occurred at both six and 15 weeks (Table 3). However, the total population avail able for evaluation and those rem aining absti nent decreased during this tim e. For example, 596 ■ I ADA, Vol. 108. ADril 1984
Significance probability
Statistic
Experimental
Placebo
Mean change (SD) Sam ple size
-1 1 .1 (11.4) 73
-1 4 .6 (12.2) 57
.091
* O n ly c o n tin u o u s sm okers are in c lu d e d . C h an g e w as d e fin e d a s th e d ifferen ce b e tw e en av erag e d a ily n u m b er of cig arettes sm o k e d at stu d y e n d v s t h e p re stu d y b a se lin e v alu e.
Table 6 ■ Daily average num ber of pieces chew ed. Six weeks
Efficacy
.046
Table 4 ■ Quit-rates at six weeks according to level of nicotine dependency.
E valuations Evaluations of the efficacy of the experimental vs placebo gum were based on self-reports of smoking cessation (by questionnaire) and con firmatory breath CO determ inations. A suc cessful quitter was defined by a self-report of abstinence and an expired breath CO value of less than 8 ppm . These evaluations were per formed six and 15 weeks after providing the gum . T he types and frequency of adverse events w ere also evaluated at these times. Group com parisons w ere m ade w ith twosid e d , tw o -sam p le t-te sts for q u an titativ e characteristics and w ith tw o-sided x2 tests for qualitative data. The single degree-of-freedom X 2 tests w ere im plem ented w ith continuity cor rection. Moreover, such tests involving absti nence rates w ere conducted as one-sided pro cedures.
(4.8)
Statistic Mean (SD) Sample size
15 weeks
Experimental
Placebo
E xperim ental
Placebo
7.6 (5.1) 62
6.7 (5.9) 69
2.8 (4.6) 27
1.8 (3.1) 34
the num ber of abstinent patients in the exper im ental group was 36 at six weeks and only 13 at 15 weeks; the decline in the num ber of suc cessful abstainers was the result of the resum p tion of smoking by 11 panelists and the w ith drawal of 12 patients from the study. Stratifying the subjects who quit smoking on the basis of Q scores (Table 4) supports the concept that heavily nicotine-dependent sub jects w ill derive more benefit from a nicotinecontaining chewing gum than will less depen dent subjects (46% vs 29%). However, even the patients in the less dependent nicotine-gum group w ere more successful in discontinuing smoking than were those in the placebo group. Among those smokers who had decreased their rate of smoking, but had not quit, no real dif ference betw een the experim ental and placebo groups was seen (Table 5). Gum usage A lthough it appears that gum usage should continue for three to four months, the study in dicated that patients down-titrated themselves (Table 6). For example, patients averaged ap proxim ately seven pieces of gum per day dur
ing the first six weeks, but were using only two to three pieces per day by the 15th week. At the stu d y end, subjective evaluation of the gum was m ade by having the study partici pants answ er three questions dealing w ith palatability, oral sensation, and helpfulness. Generally, comparable proportions of subjects found the active and placebo gums to be likable (52% and 55%, respectively), and to produce about the sam e oral discomfort (37% and 23%, respectively). However, 65% of the users of the nicotine gum , in contrast to 33% for placebo, reported the gum to be effective in helping people to overcom e smoking. S afety Table 7 lists the m ost frequently reported ad verse effects by treatm ent at two, six, and 15 weeks after gum distribution. Adverse effects w ere tabulated by the num ber of complaints received, not by the num ber of subjects report ing. The adverse events that may be attributa ble to use of the nicotine-containing gum are nausea, eructation (belching), hiccups, and jaw m uscle ache. On the basis of telephone conversations w ith the patients w ho w ithdrew
A R T IC L E S
Table 7 ■ Frequency of reported adverse effects by time and treatment condition.*______ Experimental (wk) Placebo (wk) Adverse effect
2
6
15
2
6
15
Traumatic ulcer Jaw muscle ache Nausea Hiccups GI symptoms Eructation Aphthous ulcer
21 11 13 10 8 6 5
10 7 8 6 2 1 3
32 17 18 15 11 7 6
20 5 1 0 5 1 5
11 4 3 0 1 0 2
26 10 4 0 7 1 7
‘Multiple other adverse effects were reported once or twice during the 15 weeks; such effects included cheek biting, tingl ing tongue, headache, anorexia, irritability, and tinnitus.
from the study, it was determined that none of the subjects withdrew as the result of adverse effects of gum usage.
Discussion The major fu n ction of a n ic o tin econtaining chewing gum in smoking ces sation is to alleviate the symptoms of nicotine dependence, allow ing the smoker to concentrate his or her efforts on the psychologic aspects of smoking cessa tion. The initial taste experience with the nicotine gum is aversive (few smokers like the taste initially, but grow accus tomed to it with use). Blood levels achieved by the 2-mg gum are approxi mately half that obtained with a cigarette. This may imply that the primary effect of the gum is to alleviate withdrawal rather than to produce the positive stimulatory effects of smoking cigarettes.14,15 Con sequently, smokers must be highly moti vated to quit and must be willing to con tinue gum use for at least three months. Indeed, whereas the optimal duration of use is unclear, it has been suggested that three to four months of abstinence are re quired for the strength of the habit to abate sufficiently to increase the likeli hood of success.10 In this study, patients used an average of eight pieces of the nicotine gum/day for six weeks, resulting in a quit-rate three times greater than that observed in the placebo group (34% vs 11%). However, the degree of success is less than has been reported in other studies that use behav ior modification techniques. This is prob ably the result of the minimal amount of psych ologic support the patients re ceived, being exposed to the program only at the initial visit with a reinforce ment session at two weeks. As a result, the greatest success (46%) occurred in those patients with the highest nicotine depen dent component (Q > 6). Those patients in whom the physiologic component was less intense were less successful, but still achieved a 29% quit-rate. By 15 weeks, average gum consumption had declined to approximately three pieces/day, which
is below the level of usage usually rec ommended for optimal effects. This de creased usage may reflect a lack of moti vation on the part of the subject combined with the absence of a strong maintenance component in the program. This is sup ported by the 25% dropout rate at 15 weeks. It is clear that a chewing gum contain ing nicotine is an effective adjunct to a smoking cessation program. Its use in more intensive behavioral modification p rogram s p r o d u c e d q u it-r a te s a p proximating 60% at one month, com pared with 35% for the control group.10 The difference between these latter re sults and those observed in this investiga tion suggests the need for a greater re sponsibility of the professional personnel to support the patient throughout the withdrawal period. Constant encourage ment to withdraw from smoking and to continue using the gum for at least three to four months may be expected to en hance the final results. However, from this investigation it appears that even minimal support may be effective if the nicotine gum is used by highly motivated patients.
Conclusions The results of this study suggest the po tential benefits of a nicotine-containing chewing gum in aiding smoking cessa tion efforts. After six weeks of gum usage, 36 of 105 patients (34.3%) provided the experimental chewing gum had stopped smoking as compared with only 11 of the 103 p a tie n ts (10.7% ) p r o v id ed the placebo formulation. At the end of the 15-week study the number of patients who had successfully stopped smoking throughout the test period declined ap preciably in both the experimental and placebo groups; the corresponding values were 13 of 105 patients (12.4%) vs 5 of 103 (4.8%), respectively. Nevertheless, the in tergroup differences in quit-rates were statistically significant throughout the study period. At six weeks, subjects with high nicotine dependence were consid ered separately from those w ith low nicotine dependence. A noticeable esca lation of the success rate in the high nicotine dependent group attests to the particularly beneficial role of the nicotine gum in recalcitrant smokers. The increase in quit-rates using the nicotine gum was achieved with few adverse effects that were easily tolerated in conjunction with a minimal impersonal stop-smoking ces sation program.
_________________________________________ J W O A This research was supported by Merrell Dow Pharmaceuticals, Inc, Cincinnati.
The authors thank Mr. Stephen A. Miller, MS, Mer rell Dow Pharmaceuticals, Inc, for assistance in the conduct of this study, and to Dr. Ben J. Cerimele, Mer rell Dow Pharmaceuticals, Inc, for the statistical analysis of the data. Dr. Christen is associate professor and chairman, department of preventive dentistry; Dr. McDonald is professor, department of preventive dentistry; Dr. Olson is associate professor, department of preven tive dentistry; Ms. Drook is director, clinical pro grams, Oral Health Research Institute; Dr. Stookey is professor, department of preventive dentistry, and di rector, Oral Health Research Institute, Indiana Uni versity School of Dentistry. Address requests for re prints to Dr. Christen, Oral Health Research Institute, 415 Lansing St, Indianapolis, 46202.
1. Christen, A.G. The clinical effects of tobacco on oral tissue. JADA 81(6):1378-1382,1970. 2. Bastiaan, R.J., and Reade, P.C. The effects of to bacco smoking on oral and dental tissues. Austr Dent J 21:308-315,1976. 3. US Surgeon General’s Advisory Committee on Smoking and Health. Smoking and health: report of the committee. Pub No. 1103. Washington, DC, US Government Printing Office, 1964. 4. US Public Health Service. Smoking and health: a report of the surgeon general. Jan 11,1979. US De partment of Health, Education, and Welfare, Wash ington, DC, DHEW Pub no (PHS) 79-50066. 5. American Dental Association. News of den tistry. JADA 69:776, 1964. 6. Christen, A.G. Survey of smoking behavior and attitudes of 630 American dentists attending the 1983 ADA Annual Session. JADA, to be published. 7. Noll, C.E. Health professionals and the problems of smoking and health. Report 2. Dentist’s behavior, beliefs and attitudes toward smoking and health. Na tional Opinion Research Center, NORC Survey 4001, Chicago, University of Chicago, 1969. 8. N ational C learinghouse for Sm oking and Health. Survey of health professionals: smoking and health, 1975. US Department of Health, Education, and Welfare, Public Health Service, Center for Dis ease Control, Bureau of Health Education, 1976. 9. Fagerstrom, K.O. A comparison of psychologi cal and pharmacological treatment in smoking cessa tion. J Behav Med 5:343-351,1982. 10. Jarvis, M.J., and others. Randomised controlled trial of nicotine chewing gum. Br Med J 285:537-540, 1982. 11. Raw, M„ and others. Comparison of nicotine chewing gum and psychological treatments for de pendent smokers. Br Med J 281:481-482,1980. 12. Fagerstrom, K.O. Measuring degree of physical dependence to tobacco smoking with reference to in dividualization of treatment. Addict Behav 3:235241,1978. 13. Hill, P.; Haley, N.J.; and Wynder, E.L. Cigarette smoking: carboxyhem oglobin, plasm a nicotine, cotinine and thiocyanate vs. self-reported smoking data and cardiovascular disease. J Chronic Dis 36:439-449, 1983. 14. McNabb, M.E.; Ebert, R.V.; and McCusker, K. Plasma nicotine levels produced by chewing nicotine gum. JAMA 248:865-868,1982. 15. Ness, L.; Rosenkrans, D.L.; and Welford, J.F. An epidemiological study of factors affecting extrinsic staining of teeth in an English population. Commu nity Dent Oral Epidemiol 5:55-60,1977. 16. Addy, M., and others. Chlorhexidine staining: a clinical cross-over study and dietary analysis in volunteer subjects. J Dent Res 58{Spec Issue C):12-54, 1979. 17. Prayitno, S., and others. An in vivo study of dietary factors in the aetiology of tooth staining as sociated with the use of chlorhexidine. J Periodont Res 14:411-417,1979. a 18. Russell, M.A.; Raw, M.; and Jarvis, M.J. C lin i^ fl use of nicotine chewing gum. Br Med J 280:1!^H 1602,1980.
: EFFICACY OF NICOTINE CHEWING Gl