Prevention Of Postcessation Weight Gain

Numerous behavioral and pharmacologic interventions have been developed during the past 10 years in an attempt to reduce or prevent post-cessation weight gain (see reviews by Perkins et al. (74); Perkins (75)). These efforts may seem misguided given that weight gain after quitting smoking is rather modest (typically not higher than 6 kg, on average) and less health-damaging than continued smoking. Furthermore, the actual amount of weight gain has been shown to be unrelated to outcome in some studies (76,77) or to predict continued abstinence in others (54). However, as discussed above, many smokers, particularly women, report using smoking as a weight-control strategy, and fear of gaining weight as a reason for not attempting to quit. As such, adjunct treatments that effectively address these concerns clearly are needed to optimize smoking cessation interventions. Below, both behavioral and pharmacologic strategies will be described.

Diet and Exercise Interventions

Because of the evidence that most of the cessation-induced weight gain is due to increased eating, it has been widely accepted that efforts to prevent this weight gain through dieting will improve abstinence. However, there is little direct support for this assumption and some evidence supporting the opposite notion, that attempting to prevent moderate weight gain after quitting may be detrimental. Hall et al. (78) supplemented an intensive behavioral smoking cessation program (seven hour sessions over 2 weeks) with either (1) a behavioral weight control program (five sessions over 4 weeks consisting of daily weight and calorie monitoring, encouragement to engage in aerobic exercise > 3 times per week, and behavioral self-management principles, (2) a non-specific weight control program (group therapy providing support and information on diet and exercise), or (3) standard treatment control (a printed information packet on nutrition and exercise). Unexpectedly, subjects in both weight control conditions had lower abstinence rates at end of treatgment and 1 year follow-up than those in the standard treatment. Also, weight gain was not attenuated in either of the weight control conditions relative to standard treatment, at either 6 weeks or 1 year post-treatment.

Pirie et al. (79) randomized 417 female smokers in a 2 x 2 design to receive nicotine gum vs. no gum crossed with weight control counseling vs. no weight control counseling. All four groups received behavioral smoking cessation counseling. Weight control counseling involved counseling to modestly reduce caloric intake and increase activity. At 12 months, abstinence rates were highest among subjects receiving nicotine gum only, and lowest in those who received nicotine gum plus the weight control programs.

Results from both of these large, well-conducted investigations suggest that adding a weight control component to an already intensive smoking cessation intervention provides too complicated an approach that overwhelms participants. Attempts to focus one's attention simultaneously on weight con trol and smoking abstinence may actually lead to failure to accomplish either. Another possible reason for the failure of these interventions to prevent weight gain is that reducing energy intake may lead to the loss of another powerful reinforcer (in addition to nicotine), which in turn encourages smoking. Consistent with this hypothesis is that food deprivation increases the self-administration of several drugs in animals, including nicotine (74). It may also be that eating helps to attenuate nicotine withdrawal symptoms (74). This is consistent with the results of two studies that have found that both food (80) and glucose tablets (81) reduced cravings for cigarettes during abstinence from smoking.

If the failure of these interventions to prevent weight gain is due to cognitive overload from simultaneously trying to change two behaviors, then delaying the weight control intervention until after smoking cessation had been achieved would be expected to prevent weight gain more effectively. This hypothesis is supported in preliminary data from 291 women enrolled in a 16-week behavioral smoking cessation/weight gain prevention trial (82). Subjects were randomized to receive the weight control intervention early in the program (first 8 weeks), late in the program (last 8 weeks), or to no weight control component. Although cessation outcomes did not differ among the three groups, at both 6 and 9 months post-cessation, subjects who received the weight control intervention late gained less weight than either control subjects or those who received the intervention early. These data suggest that a behavioral intervention can reduce post-cessation weight gain, without undermining smoking cessation, by delaying the weight management component.

Although promoting adherence to regular physical activity is challenging, there is evidence that incorporating physical activity into smoking cessation interventions can reduce post-cessation weight gain. In a prospective observational study of 9306 nurses who were regular smokers at baseline, change in weight over 2 years was evaluated as a function of changes in smoking status and physical activity levels. Among women smoking 1-24 cigarettes/day at baseline, those who quit without changing their exercise level gained an average of 2.3 kg more than women who continued to smoke. In contrast, women who quit gained an excess of only 1.8 kg if they increased exercise by 8-16 MET-hours/week (equivalent to 1-2 hours of vigorous activity/week), and only 1.3 kg if they increased exercise by more than 16 MET-hours/week (83).

A recently published clinical trial randomized 281 sedentary women to receive either a 12-week behavioral smoking cessation program with either vigorous aerobic exercise (three 1-hour supervised sessions of aerobic activity per week for 12 weeks) or an equal time contact control condition (health education lectures and discussions) (84). At the end of treatment, subjects in the exercise condition gained less weight than control subjects (3.05 vs. 5.40 kg, respectively). However, the groups did not differ in the magnitude of weight gain at 12 months follow-up. Unfortunately, only 10% of subjects in the exercise condition continued with regular exercise throughout the 1-year follow-up period. Thus, while exercise appears to be helpful strategy to prevent post-cessation weight gain, longer treatment periods probably are needed to sustain its effect. It is likely, however, that such an intensive approach is not appealing to many smokers. In this study, a high proportion (68%) of eligible smokers chose not to participate, and substantial loss to follow-up occurred.

Perkins et al. (74) have argued that weight gain early after cessation, even if somewhat attenuated by a weight control intervention, may be enough to discourage continued efforts to remain abstinent. While there is clear evidence that integrating a weight control component into smoking cessation interventions can attenuate weight gain, these programs have not entirely prevented weight gain. However, one study indicates that behavioral change is capable of entirely preventing weight gain, albeit in highly controlled circumstances (military boot camp) (85). Participants were 332 Air Force recruits (227 men, 105 women) undergoing 6 weeks of basic military training. A total ban on smoking was strictly enforced throughout training, and recruits underwent a rigorous program of strenuous daily physical activity (aerobics, calisthenics, drilling, marching, etc.) and ad libitum access to food at meals but no access to snack foods or between-meal eating. At the end of training, all recruits tended to lose weight, although non-smokers lost marginally more than did smokers (0.89 vs. 0.03 kg, respectively, P = 0.07). Thus, under an 'ideal' treatment environment involving increased physical activity and prohibition of snacking, post-cessation weight gain can be eliminated.

Given that post-cessation weight gain tends to be modest and does not predict success at quitting, Perkins (74) has suggested treating weight concerns rather than weight gain per se, as a potentially useful intervention. Perkins and colleagues are testing this hypothesis in an ongoing clinical trial, where a cognitive-behavioral intervention is used to challenge attitudes and perceptions regarding weight and body image. The goals of the intervention are to tolerate a modest increase in snacking and not to overreact emotionally to a modest weight increase.

Pharmacologic Interventions

Several pharmacologic strategies to prevent postcessation weight gain have been evaluated, including nicotine replacement, and both serotonin-enhancing and catecholamingeric drugs. Several clinical trials have found that nicotine gum attenuates post-cessation weight gain, at least during treatment (77,86-88). Furthermore, these effects appear to be dose-dependent (86,88). For example, Doherty et al. (86) examined weight gain through 90 days post-cessation among 79 abstinent cigarette smokers who were randomized to either placebo or 2mg or 4mg of nicotine gum. Nicotine gum was shown to suppress weight gain in a dose-dependent fashion. At 90 days post-cessation, placebo gum users gained 3.7 kg, compared to 2.1 kg and 1.7 kg for subjects receiving 2mg and 4mg of nicotine gum, respectively. A similar dose-dependent effect on weight gain was observed when the percentage of baseline cotinine levels replaced during treatment was correlated with weight gain.

Unfortunately, the weight-control benefits of nicotine gum appear to persist for only as long as the gum is used. Among patients treated with 2 mg nicotine gum in a hospital-based smoking cessation clinic, those who quit successfully for one year gained less weight if they continued to use the gum throughout the year (mean weight gain of 3.1 kg) compared to successful quitters who discontinued use of the gum (5.2 kg) (87).

In contrast to nicotine gum, the weight-attenuating effects of transdermal nicotine ('the patch') have been less consistent. In a quantitative review of four clinical trials, both placebo and transdermal nicotine groups gained weight during the periods of study, with no differences between conditions (89).

Several other studies, however, have reported reduced weight gain among patients treated with transdermal nicotine relative to placebo. For example, Abelin et al. (90) randomized patients to transdermal nicotine or placebo. After 3 months, those in the placebo group gained 4.4 kg, compared to only 0.1 kg in those receiving active treatment. Jorenby et al. (91) also examined post-cessation weight changes among patients randomized to 21 mg transdermal nicotine or placebo. Those treated with transdermal nicotine gained significantly less weight after 4 weeks (1.85 kg) than those receiving placebo (2.88 kg). Finally, Allen et al. (92) compared post-cessation weight changes among participants receiving three doses of transdermal nicotine (7, 14 and 21 mg) or placebo. Weight changes after 6 weeks were 2.5 kg (placebo), 2.03 kg (7 mg), 1.98 kg (14 mg), and 1.85 kg (21 mg), with those receiving 21 mg of transdermal nicotine gaining significantly less weight than those assigned to placebo. Thus, while some studies have reported transdermal nicotine to be associated with reduced post-cessation weight gain compared to placebo, others have found no weight attenuating effects.

Perkins (75) proposed three possible explanations for the weight-gain-attenuating benefits of nicotine gum compared to the patch. First, the differing route of administration of gum allows gum to produce more variable change in blood nicotine levels and allows for self-titration of dose. Second, the sensory and/or behavioral effects of nicotine gum may be incompatible with or otherwise discourage eating. Third, self-selection of subjects may occur in studies utilizing nicotine gum vs. patch. Nicotine gum places greater behavioral demands on subjects (in terms of frequency of chewing, following behavioral instructions) which may be related to motivational level or ability/willingness to perform other behaviors necessary to prevent weight gain.

Another possibility is that the typical doses of nicotine obtained from the patch may be insufficient to reduce weight gain. Transdermal nicotine has been found to reduce post-cessation increases in total energy, carbohydrate, and fat intake in a dose-dependent fashion (93). Additionally, in a clinical trial comparing three dosages of transdermal nicotine (11, 22, 44mg/day) among 70 subjects, weight change over 8 weeks of patch use was negatively correlated with percentage of cotinine replacement (r = - 0.38, P = 0.012) (94). Unfortunately, no studies have directly compared the weight-gain-attenuating effects of nicotine gum vs. patch at equivalent doses. One clinical trial, however, compared a combination of nicotine gum and nicotine patch (combined condition) vs. nicotine gum and placebo patch (gum only), used for 18 weeks (95). At 12 months post-treatment, weight gain was attenuated in subjects in the combined condition compared to those in the gum only condition (2.7 kg vs. 4.0 kg, respectively). Although the percentage of cotinine replaced was not measured in the study, the greater weight attenuation in the combined condition suggests a weight control benefit to the patch, possibly due to greater total dosage of nicotine replacement. Collectively, these findings suggest that the amount of nicotine that is replaced, rather than the method of administration, may have the greater impact on post-cessation weight gain.

Two newer nicotine replacement products, a nasal spray and an inhaler, have recently become commercially available in the United States. Similar to results with gum and patch, nicotine nasal spray has been shown to attenuate weight gain, but only during the period of usage. Sutherland et al. (96) randomly assigned 227 smokers to 4 weeks of group supportive treatment plus either active nicotine spray or placebo nicotine spray. Recommended duration of nasal spray usage was 3 months, but subjects were allowed to continue use beyond this time. At 12 months post-cessation, those in the placebo spray condition gained an average of 5.8 kg. Weight gain among those subjects in the active spray condition who discontinued use of spray at the end of the treatment period was similar to placebo subjects (5.5 kg). In contrast, subjects who were still using the active spray at the 12-month follow-up gained only 3.0 kg.

Two placebo-controlled clinical trials of the nicotine inhaler have examined short- and long-term effects on weight gain. Tonnesen et al. (97) found no difference in weight gain between conditions at either 6 weeks or one year post-cessation. Another study, however, found non-significant trends for the inhaler, compared to placebo inhaler, to attenuate weight gain at 2 weeks post-cessation (0.6 kg vs. 1.2 kg, respectively, P = 0.07) and 12 months postcessation (4.5 kg vs. 5.6 kg, respectively, P = 0.09) (98).

Other studies have examined non-nicotine phar-macologic strategies to prevent weight gain. Phenylpropanolamine (PPA), a catecholaminergic drug, has been found to prevent weight gain completely during 2 weeks of smoking abstinence (99). Over 4 weeks of cessation, PPA was shown to reduce weight gain by more than 50% (100). Thus, while PPA shows promise as an adjuctant pharma-cologic treatment to prevent post-cessation weight gain, no published studies have yet evaluated its long-term efficacy.

A few studies have evaluated the effects of dex-flenfluramine and fluoxetine, both serotonin-enhancing drugs, on post-cessation weight gain. In a study of 31 overweight female smokers, Spring et al. (57) demonstrated that dexfenfluramine prevented weight gain (and actually led to a small weight loss, averaging 0.8 kg) during 4 weeks of smoking abstinence compared to placebo. In another small, short-term clinical trial, fluoxetine was shown to prevent weight gain entirely (mean weight change = — 0.6 kg) compared to placebo (3.3 kg increase) among smokers who significantly reduced their nicotine intake (101). Spring et al. (102) compared the efficacy of dexfenfluramine and fluoxetine in preventing post-cessation weight gain. Subjects were 144 normal weight women, randomized to dexfenfluramine (30 mg), fluoxetine (40 mg), or placebo for 14 weeks. At 1 month post-cessation the placebo group gained more weight than either of the drug groups. By 3 months post-cessation the dexfenfluramine group had gained significantly less weight (1.0 kg) compared to either the placebo (3.5 kg) or fluoxetine (2.7 kg) groups. By 6 months post-cessation, however, weight gain was similar among the three groups. Both of these studies suggested that the weight-gain-attenuating effects of serotonin-enhancing drugs was related to suppression of the usual increases in energy intake observed after smoking cessation, particularly carbohydrates.

A recent study (103) compared the effects of two dosages of fluoxetine (30 mg vs. 60 mg) to placebo on post-cessation weight gain. During treatment, weight gain among placebo subjects was greater (2.61kg) than that of subjects receiving either 30 mg of fluoxetine (1.33 kg) or 60mg (1.25 kg). However, after discontinuing the drug, subjects who received 60 mg of fluoxetine had greater weight gain (6.5 kg) than subjects receiving either 30 mg of fluoxetine (3.6 kg) or placebo (4.7 kg). Thus, similar to the effects of nicotine replacement, serotoninergic drugs minimize post-cessation weight gain, but only for the duration of drug treatment. Unfortunately, however, the observed dose-dependent weight rebound after discontinuation of fluoxetine indicates the drug may have limited utility for the long-term prevention of post-cessation weight gain.

Two recent studies examined the effect of bup-ropion on post-cessation weight gain. Hurt et al. (104) compared weight gain among patients treated for 7 weeks with three doses of bupropion (100,150, and 300 mg) or placebo. Weight change was found to be negatively associated with dose following 6 weeks of cessation. Weight gain among those receiving placebo averaged 2.9 kg, compared with 2.3 kg among those receiving either 100 or 150 mg of bupriopion, and 1.5 kg for those in the 300 mg group. No group differences in weight gain, however, were observed at the 6-month follow-up. Jorenby et al. (105) examined post-cessation weight changes among participants in a 2 (300 mg bupropion vs. placebo) x 2 (transdermal nicotine patch vs. placebo) randomized clinical trial. Those in the combined treatment group (i.e. bupriopion plus transdermal nicotine) gained significantly less weight at 6 weeks (1.1 kg) than those in either the bupropion only (1.7 kg) or double placebo (2.1 kg) groups, and a similar but non-significant trend was observed for the patch-only group (1.6 kg). No differences in weight gain among treatment groups existed at 6 months follow-up, however. Thus, while bupropion may help to reduce post-cessation weight gain in the short term, the weight-attenuating effects do not appear to last beyond the duration of treatment.

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