Smoking cessation: Tactics that make a big difference
Quitlines, Web support, text messaging, and drugs improve quit rates—if you and your staff set the stage.
TABLE 2
Nicotine replacement therapy: Methods are similarly efficacious11
| THERAPY | OR (95% CI) | N (PARTICIPANTS/ TRIALS) | NNT | DURATION OF THERAPY | COST OF 4 WEEKS (BRAND/GENERIC)‡ |
|---|---|---|---|---|---|
| Nasal spray | 2.35 (1.63–3.38) | 887/4 | 8.3 | 3–6 months | $560/NA |
| Inhaler | 2.14 (1.44–3.18) | 976/4 | 12.5 | 3 months, then 3-month taper | $504/NA |
| Lozenges | 2.05 (1.62–2.59) | 2739/5 | 14.3 | Up to 12 weeks | $300/$240 |
| Patch | 1.84 (1.65–2.06) | 16,228/37 | 16.7 | 8–12 weeks | $110/$92 |
| NR T (all) | 1.77 (1.66–1.88) | 39,503/105 | * | ||
| Gum | 1.66 (1.51–1.81) | 17,819/52 | 12.5 | Up to 12 weeks | 4 mg: $234/$180 2 mg: $204/$150 |
| * Numbers not available. | |||||
| † Cost based on prices from Walgreen’s and Target Pharmacies, May and September 2007. | |||||
| OR, odds ratio; NNT, number needed to treat; NA, product not available. | |||||
Sustained-release bupropion: Similar results to NRT
The other first-line therapy suggested by the AHRQ guidelines is sustained-release bupropion.2,3 A separate Cochrane Review15 analyzed the data from 36 studies using antidepressants and revealed that two thirds of the studies in this meta-analysis used bupropion. The odds of quitting smoking essentially doubled in the placebo-controlled studies. This is a similar effect as NRT. Neither the AHRQ guidelines nor the Cochrane Review recommend bupropion over NRT or vice-versa.
According to the Cochrane Review, there was no benefit to increasing the dose of bupropion from 150 mg to 300 mg daily. Although the initial multi-dose study of bupropion16 showed a difference, it was not clinically significant by the end of the study. A larger, open-label randomized trial of 1524 smokers17 followed for 1 year also showed similar results. At the 3-month evaluation, the higher dose had superior efficacy, but that effect was not statistically significant by the end of the study. Lastly, there is no benefit to continuing the bupropion beyond 7 weeks after the target quit date.
With other antidepressants, results vary
The Cochrane Review also looked at other antidepressants. There were 4 RCTs of nortriptyline (Aventyl/Pamelor) without NRT, totaling 777 smokers followed for at least 6 months.18-21 The pooled data essentially doubled the odds of quitting smoking from 7.0% for the controls to 17.2% in the treated groups (OR=2.79; 95% CI, 1.70–4.59). Adding nortriptyline to NRT did increase the quit rates, but not significantly. The dose used in these studies, at 75 to 150 mg is much lower than that used for depression, where significant side effects often interfere with treatment. Generally the starting dose is 25 mg at bedtime. After 1 week, the dose is increased to 50 mg and the following week, it is increased again to 75 mg. Once on the 75 mg dose for a week, the dose is titrated up only if needed. The titration continues at an additional 25 mg weekly.
One of the 4 placebo-controlled studies20 included an arm of bupropion, producing a head-to-head assessment with nortriptyline (SOR: A). The abstinence rates as indicated by no smoking during the final week of treatment were comparable for the 2 groups receiving active medication. Treatment with bupropion or nortriptyline was significantly more efficacious than placebo. However, the effect was lost at the 1 year continuous abstinence mark; the 2 drugs did not differ from each other or placebo (TABLE 3).
Other antidepressants were evaluated in the Cochrane study.15 The tricyclic antidepressants doxepin and imipramine (Tofranil) had no long-term studies and neither showed statistically significant differences in smaller trials. Of the selective serotonin reuptake inhibitors (SSRIs), only fluoxetine (Prozac) had any long-term studies, and none noted statistically significant differences. Likewise, venlafaxine (Effexor) had only 1 trial in which the confidence interval did allow for a potentially useful clinical effect, but failed to show a statistically significant increase in 12-month quit rates.
Clonidine is an option, but side effects are an issue
Another Cochrane Review22 looked at the effectiveness of clonidine (Catapres) on smoking cessation. Most of the clonidine studies assessed withdrawal symptoms rather than abstinence. Of those that did assess quit rates, the pooled OR for clonidine compares favorably at 1.89 (95% CI, 1.30–2.74). Unfortunately, clonidine has significant side effects: sedation and postural hypotension. The starting dose is 0.1 mg twice daily, and it may be titrated up to a maximum dose of 0.4 mg daily. It should be used for 3 to 4 weeks only to decrease the symptoms of withdrawal. The smoker should then be weaned off the clonidine.
The anxiolytics were the subject of another Cochrane Review.23 This review, however, did not recommend any anxiolytics, including diazepam and buspirone, for smoking cessation.
A new category of therapy: Nicotinic receptor agonists
With the US Food and Drug Administration’s approval of varenicline (Chantix) in May 2006, a new class of drugs became available for treatment of tobacco dependence. This α4β2 nicotinic acetylcholine receptor partial agonist was designed as a smoking cessation drug. By releasing dopamine in the brain like nicotine, it prevents craving. However, it also blocks nicotine from binding, thereby preventing the reinforcing effect of continued smoking.
