Antismoking products

Nicotine is the addictive substance in tobacco and its withdrawal is responsible for a range of unpleasant symptoms after smoking cessation. Although it produces acute physiological effects, nicotine alone is not carcinogenic and does not appear to cause the vascular disease associated with smoking. Nicotine replacement has been shown to be a safe and effective pharmacological treatment for tobacco dependence in certain smokers. Its efficacy is greatest when prescribed for those who are motivated and highly nicotine-dependent. It is probably not indicated for smokers with a low degree of nicotine dependence. Studies of nicotine chewing gum conducted in special referral clinics have generally produced positive results, whereas those conducted in community practice settings have shown a smaller benefit when compared with placebo. When the results of all published placebo-controlled trials are pooled the typical improvement in smoking cessation rate is 40% (odds ratio continued smoking 0.6; 95% confidence interval 0.5-0.71; P less than 0.00001). The best results with nicotine chewing gum have been obtained with multicomponent programmes which have included some counselling and ongoing follow up and support. Early reports of success with a transdermal nicotine preparation suggest that it may have similar efficacy to nicotine gum. Clonidine administered orally or transdermally has also been shown to reduce tobacco withdrawal symptoms but requires more convincing evidence of long-term efficacy before it can be recommended for routine use. Currently available over-the-counter products, apart from nicotine chewing gum, have not been shown to be effective.     

Minimal contact treatment for smoking cessation. A placebo controlled trial of nicotine polacrilex and self-directed relapse prevention: initial results of the Stanford Stop Smoking Project

To determine the effectiveness of nicotine polacrilex combined with self-administered relapse prevention materials in maintaining smoking cessation, we conducted a randomized, double-blind, placebo controlled trial. Volunteers aged 18 to 65 years responding to media announcements were required to quit smoking for 48 hours without assistance. Of 1844 potential participants, 136 were medically excluded, 535 declined to make a quit attempt, and 573 were unable to quit, leaving 600 participants (35%) who were randomized. Eight self-help relapse prevention modules were mailed weekly. Gum was used either ad lib for smoking urges or on a fixed, hourly schedule (12 pieces per day). Only 15% of the subjects in each gum group stopped using the gum altogether because of side effects, but only 20% of the ad lib groups and 40% of the fixed-dosage group used at least eight pieces of gum per day during the first week. The abstinence rates (for at least seven days) at the six-month follow-up were 31% in both active gum groups and 22% in the placebo and no gum groups. Relapse rates in the two active gum groups were about half those in the placebo and no gum groups. Nicotine polacrilex may be a useful adjunct to minimal contact smoking cessation formats, which have broad appeal. Also, minimal contact relapse prevention programs may assist physicians in helping patients to maintain smoking cessation using nicotine polacrilex.     

Nasal nicotine solution: a potential aid to giving up smoking?

A nasal solution was developed containing 2 mg nicotine for use as a kind of liquid snuff. Its absorption was studied in three subjects. An average peak of plasma nicotine concentrations of 86.9 nmol/l (14.1 ng/ml) was reached seven and a half minutes after taking the solution. This compared with an average peak of 158.4 nmol/l (25.7 ng/ml) one and a half minutes after completing (but seven and a half minutes after starting) a middle tar cigarette (1.4 mg nicotine) and an average peak of 52.4 nmol/l (8.5 ng/ml) after chewing nicotine gum (2 mg nicotine) for 30 minutes. The more rapid and efficient absorption of nicotine from the nasal nicotine solution than from nicotine chewing gum suggests that it might prove a useful aid to giving up smoking. Nasal nicotine solution might be particularly useful in smokers for whom the gum is less suitable on account of dentures or peptic ulcers or who experience nausea and dyspeptic symptoms from the gum.     

A randomized trial of a family physician intervention for smoking cessation

We assessed the impact of three conditions on one-year smoking cessation rates. Physicians in 70 community general practices were randomly allocated by practice to one of three groups: In the usual care group, smoking patients were to receive the care they normally would receive. In the gum only group, physicians were asked to speak to patients about smoking cessation and offer nicotine gum. In the gum plus group, physicians were trained in the experimental intervention. This intervention involved advice to stop smoking, the setting of a quit date, the offer of nicotine gum, and four follow-up visits. Smoking cessation was measured by self-report after one year and validated using saliva cotinine measures. Using a criterion of at least three months of abstinence, 8.8% of the patients of the trained physicians had stopped smoking at the one-year follow-up compared with 4.4% and 6.1% of the patients in the usual care and gum only groups, respectively.     

Research letter: Intentions of smokers to use free nicotine replacement therapy

Public health initiatives to distribute nicotine replacement therapy free of charge as a means of promoting smoking cessation are ongoing. Are there enough smokers interested in using nicotine replacement therapy to have a substantial impact on the prevalence of smoking if this aid were distributed free to all interested smokers? We conducted a telephone survey of 825 randomly selected daily smokers aged 18 years or older who had smoked at least 10 cigarettes per day at some point in their lives. Overall, 58.9% of the respondents said they would be interested in nicotine replacement therapy if it were offered for free. Of those interested, almost all (93.8%) said that they would use the nicotine replacement therapy to help them quit for good. There were differences in the levels of interest: smokers who intended to quit were more interested in using the nicotine replacement therapy than those who planned to reduce or maintain their smoking.     

Heavy smokers, smoking cessation, and clonidine. Results of a double-blind, randomized trial

Seventy-one heavy smokers who had failed in previous attempts to stop smoking participated in a randomized clinical trial to test the efficacy of clonidine as an aid in smoking cessation. The success rate in clonidine-treated subjects (verified by serum cotinine concentration) was more than twice that in the placebo-treated subjects. When the data were stratified by gender, a strong effect present in women was not apparent in men. After six months, cessation rates remained significantly higher among smokers treated with clonidine than those receiving placebo. The data also revealed an unexpectedly high prevalence (61%) of a history of major depression in this sample and a significant negative effect of such a history on cessation regardless of treatment. These findings, highly suggestive of an important role of clonidine in smoking cessation, warrant further studies to establish the long-term (greater than or equal to 12 months) efficacy of this drug and to replicate the association between nicotine dependence and depression.     

Nicotine chewing gum in general practice: effect of follow up appointments

Two hundred smokers who were judged by their general practitioner to be motivated to stop smoking were allocated to one of two groups. All were offered an initial appointment at which they were advised to stop smoking and offered nicotine gum. One group then received no further appointments. The other was offered four further appointments over three months. Both groups were followed up at six and 12 months. At one year follow up 15.5% overall had stopped smoking, 14% in the low and 17% in the high contact group. This is better than most results so far reported for nicotine chewing gum in general practice, suggesting that general practitioners can use it to good effect. We compare this result with others achieved in general practice.     

Physical dependence on nicotine in gum. A placebo substitution trial

To test whether ex-smokers become physically dependent on nicotine in gum, we entered eight ex-smokers who were using nicotine gum into a randomized, double-blind, placebo-substitution trial. When placebo was substituted, seven of the eight subjects were observed to have withdrawal symptoms and two relapsed to smoking or nicotine gum. This result suggests that physical dependence (ie, withdrawal) may be a cause of behavioral dependence on nicotine gum (ie, use of gum beyond the recommended period) and physicians should emphasize the need for gradual reduction of nicotine gum.     

Randomised controlled trial of nicotine chewing-gum

The effectiveness of 2 mg nicotine chewing-gum as an aid to stopping smoking was compared with a placebo containing 1 mg nicotine, but unbuffered, in a double-blind randomised trial. Of 58 subjects given the active gum, 27 (47%) were not smoking at one-year follow-up compared with 12 (21%) of the 58 subjects treated with placebo (p less than 0.025). By the most stringent criterion of outcome, 18 (31%) subjects in the active treatment group and eight (14%) in the placebo group had not smoked at all from the start of treatment to follow-up at one year (p less than 0.05). Subjects receiving the active gum experienced less severe withdrawal symptoms and rated their gum as more helpful than did the placebo group. Minor side effects were common but only gastric symptoms were more frequent with the active gum. Subjects receiving active gum used it for longer than those receiving placebo but most stopped using it within six months and only four (7%) developed longer-term dependence. The number of gums used daily correlated significantly with pretreatment blood nicotine concentrations in the active treatment group and with pretreatment cigarette consumption in the placebo group. A lower pretreatment blood nicotine value was the best predictor of success at one year (p less than 0.001) but there was no significant relation to cigarette consumption, sex, and social class. The results clearly confirm the usefulness of nicotine chewing-gum as an aid to stopping smoking and imply a definite role for nicotine in cigarette dependence and withdrawal. Successful use of the gum requires careful attention to subjects' expectations and clear instructions on how to use it.     

The pharmacotherapy of smoking cessation

1. The great majority of smokers are chronically dependent on tobacco. This dependence arises from the rituals and sensory associations of smoking that are reinforced, within seconds, by a rapid burst of nicotine from the cigarette. 2. All forms of nicotine replacement therapy (NRT) -- gum, patches and inhaler -- and bupropion are safe and effective for increasing smoking cessation rates in the short and long terms. 3. Other than those who are minimally dependent, all patients willing to quit should be offered one of these therapies unless contraindications exist. The effectiveness of drug treatments is multiplied when associated with effective counselling or behavioural treatments. 4. While NRT is not recommended during pregnancy or in patients with cardiac disease, if the alternative is smoking NRT is almost certainly safe. 5. Combination NRT (more than one therapy) may be indicated in patients who have failed monotherapy in association with withdrawal symptoms. 6. There are some specific contraindications to the use of bupropion. Its subsidised availability should not influence prescribers to ignore these.     

Internists and nicotine gum

Nicotine gum may be a useful aid to help patients quit smoking. The effectiveness of the gum and incidence of side effects may depend on using the gum properly. To describe internists' current practices of prescribing nicotine gum and other drugs for smoking cessation, we surveyed randomly selected internists. Most internists prescribe nicotine gum to fewer than 25% of patients who try to quit smoking. Contrary to current recommendations, nearly half of internists would suggest gum to help patients cut down on smoking, and a majority would limit its use to less than three months. There is no evidence that sedatives are useful for smoking cessation, but one fourth of internists had recently prescribed them for that purpose. There is a widespread need for physician education about how to use nicotine gum more effectively.     

Effects of nicotine chewing gum on UPDRS score and P300 in early-onset parkinsonism

It has been reported that nicotine shows some beneficial effects on Parkinson's disease. The purpose of the present study is to assess the therapeutic effects of nicotine chewing gum in patients with early-onset parkinsonism (EOP). The subjects were 8 patients with early-onset parkinsonism (male/female = 4/4, mean age; 51.3 years). Four out of 8 patients had a history of smoking (smokers). To estimate the effects of nicotine gum, the scores on the Unified Parkinson's Disease Rating Scale (UPDRS) and auditory event-related potentials (ERPs) were studied before and after taking nicotine gum in the EOP patients. In smokers, UPDRS scores improved by more than 10% and the P300 latency of auditory ERPs was shortened by more than 30 msec. In contrast, nicotine had no remarkable effects on UPDRS scores or auditory ERPs in non-smokers. We suggest that nicotine chewing gum may be a possible choice for the treatment of patients with EOP, especially when they are smokers.     

Mobilizing physicians to conduct clinical intervention in tobacco use through a medical-association program: 5 years' experience in British Columbia.

During the last 5 years, a program run by the medical association in British Columbia has recruited 23% of the province's general practitioners (GPs) to take an active, systematic approach to clinical intervention in tobacco use. Another 9% of GPs (considered "semi-active") regularly use the program's educational materials for patients, and another 25% have been trained in intervention or have been given intervention materials or both. If the cessation rate (rate of patients who quit smoking who would not otherwise have done so) was 4% among physicians actively involved in intervention and 2% among physicians considered semi-active, in 1995 an estimated 4700 smokers quit and were followed by their GPs as a result of the program. Another 135,000 smokers received brief counselling from their GPs and were also followed. This article reviews the strategies and methods used in this program to mobilize physicians.     

A smoking cessation intervention program for family physicians.

Family physicians are able to approach many patients who smoke but are often hesitant to help them quit. Lack of knowledge about effective interventions is a major reason for this hesitancy. The important components that have been tested in physician-initiated smoking cessation interventions are advice to quit, information about the risks of smoking and techniques for quitting, nicotine gum, setting a date for quitting and offers of supportive follow-up visits. We describe a cessation program developed for family physicians that incorporates these factors into three types of visits over a 2-month period: the challenge visit, which occurs during a regular office visit and focuses on advice and setting a date to quit; the quit-date visit, which involves instructing patients on the proper use of nicotine gum, if applicable, and confirming their desire to quit; and four supportive follow-up visits, which provide continuing encouragement for 2 months and allow physicians to monitor withdrawal symptoms, relapses and other problems. Such a program can be effectively incorporated into a general practice.     

Treatment of acute migraine with subcutaneous sumatriptan.

Sumatriptan succinate, a 5-HT1D receptor agonist, constricts human cranial arteries. Two parallel-group trials for treatment of acute migraines were conducted in the United States. Adult patients were randomized and given either 6 mg of sumatriptan succinate subcutaneously (n = 734) or placebo (n = 370). At 1 hour, sumatriptan was significantly more effective than placebo in reducing moderate or severe headache pain to mild or no pain (70% vs 22%), in completely relieving headaches (49% vs 9%), and in improving clinical disability (76% vs 34%). Sumatriptan also reduced nausea and photophobia significantly better than placebo. Patients with residual migraines received another injection; those who had originally received sumatriptan received either a second active injection (n = 187) or placebo (n = 178), while those who had received placebo received a second placebo injection (n = 335). Statistical evidence for benefit of second sumatriptan injection is absent. Adverse events associated with sumatriptan were tingling, dizziness, warm-hot sensations, and injection-site reactions. Sumatriptan is effective and well tolerated in patients with acute migraine.     

The effects of supplementary nicotine in regular cigarette smokers

Blood nicotine levels were measured in eight subjects over a 5-week period, while smoking normally, while smoking and chewing gum containing 2 mg nicotine, and while smoking and chewing placebo gum. Despite a small but significant rise in blood nicotine levels during the period of the nicotine gum chewing (mean 35.3 ng/ml) compared with placebo (mean 28.9 ng/ml) and control (mean 26.3 ng/ml), cigarette consumption butt lengths, filter nicotine and blood carboxyhaemoglobin levels did not change indicating that there had been no significant changes in smoking patterns. The reasons for this failure to demonstrate an effect are discussed. It is concluded that the dose of nicotine used was probably not adequate to produce an effect.     

Chewing nicotine gum for 3 months: what happens to plasma nicotine levels?

Techniques that help patients stop smoking should also reduce their exposure to agents such as nicotine. The mean plasma nicotine levels in 50 subjects while they were still smoking and then while they were chewing pieces of gum containing either 2 or 4 mg of nicotine over a 12-week period of abstinence were 35, 9 and 23 ng/mL (217, 56 and 143 nmol/L) respectively. A small number of subjects given an unlimited supply of gum used 14 to 24 pieces of 4-mg gum daily and had plasma nicotine levels exceeding the levels achieved while smoking. There were no acute symptoms necessitating medical intervention associated with these excessive levels. Side effects were uncommon and usually controllable. When simple dosage rules are followed people who chew nicotine gum for a few months to stop smoking lower their exposure to nicotine.     

Behavioral and pharmacological treatment methods for pregnant smokers: issues for clinical practice

Active and passive exposure to tobacco smoke are the most serious and preventable causes of poor maternal, fetal, and infant outcomes in the United States. Unfortunately, the majority of pregnant smokers do not quit smoking before or during pregnancy or after childbirth. We describe a standardized behavioral counseling model and discuss issues to consider in recommending the use of pharmacotherapy during pregnancy. Although the Food and Drug Administration no longer classifies nicotine replacement therapy (NRT) as contraindicated during pregnancy, precautions should be carefully considered for use in this population. This paper provides a synopsis of the risks of exposure to tobacco smoke during pregnancy and the postpartum; estimates the population at risk and the potential for increased cessation if effective health education methods during pregnancy were routinely provided; presents a meta-analysis of "best practice" patient education methods for pregnant smokers; and estimates the number of pregnant heavy smokers who might be eligible for NRT. We suggest five issues for the physician to consider before recommending NRT medications to pregnant patients who are heavy smokers. The judicious use of NRT medications may significantly reduce harm to the infants of heavy smokers. More evidence derived from large population-based research, however, is needed to provide guidance to the physician about NRT eligibility, dose, scheduling, and effectiveness in clinical practice.     

Methods used to quit smoking in the United States. Do cessation programs help?

Using data from the 1986 Adult Use of Tobacco Survey, we analyzed smoking-cessation methods used by adult smokers in the United States who tried to quit. About 90% of successful quitters and 80% of unsuccessful quitters used individual methods of smoking cessation rather than organized programs. Most of these smokers who quit on their own used a "cold turkey" approach. Multivariate analysis showed that women, middle-aged persons, more educated persons, persons who had made more quit-smoking attempts, and, particularly, heavier smokers were most likely to use a cessation program. Daily cigarette consumption, however, did not predict whether persons would succeed or fail during their attempts to quit smoking. Rather, the cessation method used was the strongest predictor of success. Among smokers who had attempted cessation within the previous 10 years, 47.5% of persons who tried to quit on their own were successful whereas only 23.6% of persons who used cessation programs succeeded. We conclude that cessation programs serve a small, but important, population of smokers that includes heavier smokers, those most at risk for tobacco-related morbidity and mortality.