Update on pharmacologic and nonpharmacologic therapies for smoking cessation

Quality of evidence

MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews (Cochrane Tobacco Addiction Group) were searched. Search terms and MeSH headings used included smoking, smoking cessation, tobacco use disorder, varenicline, Champix, Chantix, bupropion, Zyban, nicotine replacement therapy, nicotine, and counseling. No limitations were placed on the search. Reference lists in selected articles were reviewed to identify additional relevant information. Randomized controlled trials, meta-analyses, and systematic reviews (level I evidence) were assessed.

Nicotine replacement therapy

Nicotine replacement therapies (NRTs) available in Canada include nicotine gum, patches, and inhalers. These therapies aid in smoking cessation by replacing the nicotine-mediated neuropharmacologic effects achieved by smoking.7 Authors of a systematic review and meta-analysis, which reviewed randomized trials of NRT compared with placebo or no treatment that had follow-up periods of 6 months or longer, determined that NRT doubles the likelihood of smoking cessation compared with no therapy (odds ratio [OR] 1.77, 95% confidence interval [CI] 1.66–1.88).8 Evidence also indicates that the nicotine patch combined with another NRT is more effective than any single NRT.9 Treatment length, dosage, and efficacy of nicotine gum, patches, and inhalers are outlined in Table 1.8,10,11 The potential side effects of nicotine gum include upset stomach, hiccups, and sore jaw. Nicotine patches are associated with headaches, upset stomach, dizziness and nausea, sleep disturbances, and rash at the site of patch application. Adverse effects experienced by users of nicotine inhalers include throat and nasal irritation, runny nose, sneezing, and coughing.12

Bupropion

Bupropion (Zyban) was launched as a smoking cessation aid in 1997 in the United States and has been approved in more than 50 countries.13 Bupropion blocks the reup-take of dopamine and norepinephrine, which is thought to be the mechanism behind its effect on smoking cessation.14 In a systematic review and meta-analysis of 31 bupropion trials in which bupropion was the sole agent used for cessation (compared with placebo or no pharmacotherapy), with 6 months follow-up or longer, the reviewers found the likelihood of cessation almost doubled with bupropion therapy (Table 18,10,11).10 Additional treatment with bupropion after cessation did not provide significant long-term advantage. Bupropion alone or in combination with the nicotine patch has been found to significantly increase long-term cessation rates compared with the patch alone (P < .001). The greater abstinence rate with combination therapy compared with bupropion alone, however, was not statistically significant.15 The most common side effects associated with bupropion are dry mouth and insomnia. Additionally, the risk of seizures is thought to be 1 in 1000, and is associated with risk factors such as seizure disorders and eating disorders.16

Varenicline

A new agent, varenicline (Champix), was introduced in Canada in April 2007.17,18 Varenicline is the first partial agonist of the α4β2 nicotinic acetylcholine receptor to be developed. The dependency effects of nicotine are thought to be mediated at these receptors.19 Varenicline might diminish withdrawal symptoms (agonist effect) and reduce craving (antagonist effect); and, with nicotine exposure, the receptor occupancy of varenicline is expected to block the reinforcing effects of nicotine.20 The most common side effect associated with varenicline is nausea. Other side effects include insomnia and abnormal dreaming.11,21

Another systematic review and meta-analysis assessed the efficacy and safety of varenicline22 by reviewing randomized controlled trials in which varenicline was compared with placebo. Comparisons with bupropion were included when available (see Table 18,10,11 for the results of one of these trials11). The outcome measure was continuous abstinence at 6 months or longer from the start of treatment. Almost 5000 individuals participated in the selected studies, of which 2451 received varenicline. Participants were men and women aged 18 to 75 years who had smoked more than 10 cigarettes daily with no period of abstinence greater than 3 months in the previous year. The treatment period was 12 weeks, with the exception of 1 study in which patients were treated for 6 weeks, and abstinence was determined by expired carbon monoxide levels. Five studies comparing varenicline with placebo fit the study inclusion criteria, and 4 were selected for meta-analysis. (The trial not included was a safety trial of varenicline compared with placebo [52-week treatment], with cessation measured as a secondary outcome.) Participants who were lost to follow-up or who withdrew were considered continuing smokers in the analysis. Researchers assessed continuous abstinence at 52 weeks for those taking 1 mg of varenicline twice daily compared with those taking placebo. The effects of titration and dosage were examined in 2 of the studies (phase 2 trials). The pooled OR for continuous abstinence at 52 weeks for varenicline compared with placebo was 3.22 (95% CI 2.43–4.27); at 24 weeks the OR was 3.53 (95% CI 2.74–4.54); and at 12 weeks (end of treatment) the OR was 4.07 (95% CI 3.28–5.05). Three trials also compared varenicline to bupropion (150 mg twice daily); the OR was 1.66 (95% CI 1.28–2.16). Nausea, the most common side effect, was largely mild or moderate and not associated with high study discontinuation rates. Findings from the trials indicated a reduction in withdrawal and cravings; however, investigators did not assess these beyond the week following treatment, so it is not known to what extent withdrawal symptoms and cravings were experienced after completion of treatment.

Nonpharmacologic treatment

Nonpharmacologic cessation strategies include brief interventions, such as patient education and advice, behavioural therapy, self-help materials, and telephone counseling (Table 223–26).23 Brief physician advice has been shown to be effective in increasing the likelihood of cessation, and follow-up likely offers further benefit.24 A review of randomized or quasi-randomized trials of individual behavioural counseling for smoking cessation by trained therapists not involved in routine medical care, with 6 months or longer follow-up, indicated that individual counseling was more effective than no intervention at all. Counseling consisted of 1 or more face-to-face sessions of 10 minutes or longer, often accompanied by telephone contact for support. Evidence was insufficient to determine whether more intensive counseling was more effective.25 Group counseling is more effective than self-help and other less intensive intervention methods for smoking cessation. It is unclear if group counseling is more effective than individual counseling, but it is more effective than no intervention.26 Self-help materials might improve quit rates among smokers compared with those who receive no intervention, but the effect is small.27 Proactive telephone counseling, in which the counselor initiates client contact, enhances the benefit of telephone counseling relative to reactive counseling, in which the client initiates contact. Multiple sessions of call-back counseling improve quit rates.28 Web-based cessation programs have been found to be effective in smoking cessation29,30; however, more research is needed.31 An example of a smoking cessation flow sheet is available from the Clinical Tobacco Intervention Program at www.ctica.org/new_fee_code_cessation.pdf.

Combined therapy

Pharmacotherapy and counseling should be used in conjunction to further improve the chances of successful cessation.5,6 Brief counseling combined with NRT has been found to be more effective than counseling alone in a randomized study of hospital patients receiving smoking cessation interventions.32 Intensive cognitive behavioural therapy initiated in-hospital, with 3 months of follow-up telephone counseling combined with 2 months of nicotine patch therapy, has been compared with hospital-initiated minimal counseling combined with nicotine patch therapy and found to be more effective for achieving long-term cessation.33 In another randomized study of telephone counseling combined with nicotine patch therapy, individuals who received both counseling and NRT had significantly greater abstinence rates compared with those who received NRT alone (28-day abstinence, P = .01 at 6 months; 90-day abstinence, P = .004 at 6 months).34