Smoking Cessation Nicotine Replacement Therapy


Treatment with NRT aims to replace the nicotine obtained from cigarettes, thus reducing withdrawal symptoms when stopping smoking. Various forms of NRT such as gum, patches, inhalers, nasal spray, sublingual tablets and lozenges have been found to be efficacious and well tolerated.20


The efficacy of NRT in smokers with COPD has been analysed in several clinical trials.18,21,22


The Lung Health Study was a multicentre,


randomised controlled trial designed to determine whether a programme incorporating a smoking cessation intervention and regular use of an inhaled bronchodilator in smokers at high risk of COPD can slow down the annual decline in lung function (forced


expiratory volume in one second [FEV1]).The results showed that after 12 months, nicotine gum in combination with an intensive behavioural programme was significantly more effective in helping smokers at risk for COPD to abstain from smoking than the usual care.21


Nevertheless,


it should be mentioned that this study made no attempt to compare NRT versus placebo. The efficacy of NRT could be confounded by the fact that the subjects who received NRT also received extensive counselling support.


Another open randomised study evaluated the efficacy of four different forms of NRT in COPD smokers. The average success rate for the active treatments was 5.6 % (p<0.01).22


The first randomised


controlled trial to demonstrate the efficacy of NRT for smoking cessation in patients with all stages of COPD has recently been published.18


This trial enrolled 370 COPD smokers that were treated


with a nicotine 2 mg sublingual tablet or placebo for twelve weeks combined with either a low level of support or a high level of support by nurses. Smoking cessation rates were statistically significantly superior with active treatment compared with placebo at both the six- and 12-month follow up, 23 % versus 10 % and 17 % versus 10 %, respectively. There was no significant difference in effect between patients receiving a low level of support versus a high level of support.18


More recently, Strassmann et al. performed a study to rank the order of effectiveness of smoking cessation interventions for COPD patients. They searched ten databases to identify randomised trials of smoking cessation counselling (SCC) with or without pharmacotherapy or NRT. They conducted a network meta-analysis using logistic regression analyses to assess the comparative effectiveness of smoking cessation interventions while preserving the randomisation of each trial. The analysis of 7,372 COPD patients showed that SCC in combination with NRT had the greatest effect on prolonged abstinence rates versus usual care (OR 5.08, p<0.0001) versus SCC alone (2.80, p=0.001) and versus SCC combined with an antidepressant (1.53, p=0.28). The second most effective intervention was SCC combined with an antidepressant (3.32, p=0.002) versus SCC alone (1.83, p=0.007), with no difference between antidepressants. SCC alone showed borderline superiority compared with the usual care (1.81, p=0.07).23


In a recent study, we reported the results of a study of 116 smokers, most of them suffering from COPD, who attended our Smoking Cessation Service but who did not want to quit abruptly. The subjects participated in a two-stage programme consisting of a four-month reduction phase followed by a six-month abstinence phase. The aim was to reduce the number of cigarettes smoked daily by at least 50 %


108


by week eight and to quit at the end of week 16. During the reduction phase, subjects used nicotine gum (2 or 4 mg) to decrease smoking progressively. During the abstinence phase, subjects used any type of NRT to remain smoke free. The results at month 2 showed that 76 subjects (68 %) achieved the target of 50 % reduction. At the target quit date in week 16, 66 subjects (57 %) achieved carbon monoxide-validated abstinence and 45 subjects (39 %) maintained continuous abstinence at the six-month follow-up.24


This study shows


that the smoking reduction approach can be effective in helping these smokers to quit. Table 1 shows some recommendations for using NRT in patients with COPD.


Bupropion


Bupropion is known to act on the nucleus accumbens, inhibiting neuronal reuptake of dopamine. This effect would explain the reduction in craving experienced by smokers who take it. It also inhibits neuronal reuptake of noradrenaline in the nucleus ceruleus, thus achieving a significant reduction in the intensity of the nicotine withdrawal syndrome.25


Treatment with bupropion should be initiated about one week before the patient's stop date at an initial dose of 150 mg/day and then 150 mg twice a day. The usual length of treatment is six to 12 weeks, but bupropion can be used safely for much longer. The most common adverse effects are insomnia and dry mouth. A small risk (0.1 %) of seizure is also associated with bupropion.26


Three clinical trials have analysed the efficacy of bupropion in the treatment of smokers with COPD.24–26


In one trial, it was found that


bupropion was significantly more effective than placebo for achieving continuous abstinence by the six month follow-up, 16 % versus 9 % (p>0.05).27


A more recent study compared the efficacy of bupropion with placebo and nortriptyline in smokers with COPD or at risk of suffering COPD. It was found that bupropion was more effective than placebo for achieving continuous abstinence by the six-month follow-up, 27.9 % versus 14.6 % in the COPD group of smokers, but was not in the group of patients at risk of suffering COPD.28


Another study has compared the efficacy and the cost-effective relationship between bupropion and nortriptyline in smokers at risk or with existing COPD.29


A total of 255 participants received smoking


cessation counselling and were assigned bupropion, nortriptyline or placebo randomly for twelve weeks. Prolonged abstinence from week


EUROPEAN RESPIRATORY DISEASE


Table 1: Recommendations for Using Nicotine Replacement Therapy in Patients with Chronic Obstructive Pulmonary Disease


Smokers with chronic obstructive pulmonary disease (COPD) can suffer from higher nicotine dependence than ‘healthy’ smokers. Adequate replacement percentages are not obtained with the nicotine replacement therapy (NRT) doses generally used. COPD patients can need higher doses of NRT A combination of different forms of NRT can be used as valid strategies to help COPD patients to quit. The combination of two types of NRT with different types of delivery is strongly recommended


Increasing the length of time that NRT is used to up to six or twelve months can help more smokers to quit than using NRT for the usual time NRT can be used to help in the progressive reduction of the number of cigarettes smoked as a gateway to quitting permanently. COPD smokers are usually unmotivated to quit. Using this approach can help them to increase their motivation and to build up their self-efficacy in quitting


COPD = chronic obstructive pulmonary disease; NRT = nicotine replacement therapy.


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