A nicotine patch plus nicotine nasal spray was more effective than a nicotine patch alone for smoking cessation
ACP J Club. 1999 July-Aug;131:12. doi:10.7326/ACPJC-1999-131-1-012
Blondal T, Gudmundsson LJ, Olafsdottir I, Gustavsson G, Westin A. Nicotine nasal spray with nicotine patch for smoking cessation: randomized trial with six year follow up. BMJ. 1999 Jan 30;318:285-9.
Is a nicotine patch plus nicotine nasal spray more effective than a nicotine patch alone for smoking cessation?
Randomized, double-blind, placebo-controlled trial with 6-year follow-up.
239 persons aged 22 to 66 years (mean age 42 y, 67% women) who had smoked ≥ 1 cigarette/d for ≥ 3 years. Exclusion criteria were recent myocardial infarction, severe nasal allergy, skin disease, use of smokeless tobacco, current misuse of alcohol, pregnancy, or lactation. Follow-up was 98%.
Participants were allocated to 5 months of nicotine patch at daily doses of 15 mg for 3 months, 10 mg for the 4th month, and 5 mg for the 5th month, plus 1 year of either nicotine nasal spray, 0.5 mg/dose (n = 120), or placebo spray (n = 119). Group support meetings and individual follow-up were provided.
Main outcome measures
Duration and rate of sustained abstinence from smoking were measured from day 1 of smoking cessation. Abstinence was defined as not taking a single puff of a cigarette, not using other forms of tobacco or nicotine drugs, or a carbon monoxide concentration < 10 ppm.
Participants who received a nicotine patch plus nicotine nasal spray had higher abstinence rates than those who received a nicotine patch plus placebo spray at 15 days (P = 0.004), 6 weeks (P = 0.011), 3 months (P = 0.045), 6 months (P = 0.005), and 1 year (P = 0.001) and a trend toward a higher abstinence rate at 6 years (P = 0.08) (Table).
Use of a nicotine patch for 5 months plus nicotine nasal spray for 1 year was more effective than a nicotine patch alone for smoking cessation. Definite differences in sustained abstinence rates at 1 year persisted as a trend at 6 years.
Source of funding: Pharmacia & Upjohn.
For correspondence: Dr. T. Blondal, Reykjavik Health Care Centre, Baronstigur 47, 101 Reykjavik, Iceland. FAX 354-562-2415.
Table. A nicotine patch plus nicotine nasal spray vs a nicotine patch plus placebo spray for abstinence from smoking*
|Follow-up||Patch and nicotine spray||Patch and placeo spray||RBI (95% CI)||NNT (CI)|
|15 d||70%||52%||35% (10 to 67)||5 (3 to 17)|
|6 wk||51%||34%||48% (9 to 101)||6 (4 to 26)|
|3 mo||37%||25%||48% (1 to 119)||8 (4 to 393)|
|6 mo||31%||16%||96% (21 to 221)||6 (4 to 22)|
|1 y||27%||11%||148% (40 to 348)||6 (4 to 16)|
|6 y||16%||8%||92% (-5 to 291)||Not significant|
*Abbreviations defined in Glossary; RBI, NNT, and CI calculated from data in article.
Despite higher cigarette prices, tougher anti-smoking laws, and attempts to hold tobacco companies responsible for smoking-related medical costs, smoking cessation remains a huge public health challenge. Blondal and colleagues point out that nicotine patch therapy alone gives an abstinence rate of only 11% after 1 year. Such results have prompted the search for better single or combination smoking cessation therapies, including combined nicotine patch and spray. Unlike previous studies, Blondal and colleagues followed patients for an extended period—6 years. Up to the end of the first year, combination therapy led to a higher abstinence rate than did the patch and placebo spray. Few patients used the spray for up to 1 year. Combination therapy showed a trend toward a higher abstinence rate at 6 years, which suggests a possible long-term benefit.
It is unclear whether the higher success rate of combination therapy was because of higher sustained concentrations of nicotine or a brief effect on concentration of the spray delivery system. The spray quickly provides a dose of nicotine that may relieve temporary cravings associated with relapse of smoking.
Nicotine replacement therapy is one approach to smoking cessation management. Mood is closely related to nicotine consumption. The antidepressant bupropion has been shown to be an effective smoking cessation aid (1). In their well-designed, double-blind, controlled trial, Jorenby and colleagues showed that bupropion, used either alone or in combination with the nicotine patch, was more effective than the patch alone or placebo for smoking cessation. A direct comparison of the 1-year continuous abstinence rates across the 2 studies shows interesting results: The rate for the patch-spray combination in the study by Blondal and colleagues was 27%, which is similar to that for bupropion alone (18.4%) or the bupropion-patch combination (22.5%) in the study by Jorenby and colleagues.
Jorenby and colleagues followed patients for only 1 year. The continuous abstinence rate beyond 1 year still needs to be studied. The fact that such high intermediate-term continuous abstinence rates can be achieved, however, should prompt physicians to consider bupropion in addition, or as an alternative, to nicotine replacement therapy.
Patients in both studies were highly motivated and received adjunctive supportive counseling. These circumstances may not apply to a larger population of persons who smoke and have some desire to quit. Extensive supportive counseling is time-consuming, expensive, and difficult to obtain without access to properly trained professionals. The feasibility and success of these therapies in ambulatory care settings need to be determined.
Another important question that has not been addressed is the effectiveness of antidepressants other than bupropion for smoking cessation. With nicotine replacement therapy already available in patch, spray, and gum forms, evidence of the effectiveness of other mood-altering drugs will add to the smoking cessation management choices available to patients and physicians.
Goutham Rao, MD
University of Pittsburgh Medical Center-St. MargaretPittsburgh, Pennsylvania, USA