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A nicotine patch plus nicotine nasal spray was more effective than a nicotine patch alone for smoking cessation
  1. Goutham Rao, MD
  1. University of Pittsburgh, Medical Center—St Margaret, Pittsburgh, Pennsylvania, USA

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Question Is a nicotine patch plus nicotine nasal spray more effective than a nicotine patch alone for smoking cessation?


Randomised, double blind, placebo controlled trial with 6 years follow up.


Reykjavik, Iceland.


239 people aged 22–66 years (mean age 42 y, 67% women) who had smoked ≥1 cigarette/day 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 patches at daily dosages of 15 mg for 3 months, 10 mg for the fourth month, and 5 mg for the fifth month, plus 1 year of either a nicotine nasal spray, 0.5 mg/dose (n=120), or a 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.

Main results

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 towards a higher abstinence rate at 6 years (p=0.08) (table).

A nicotine patch plus nicotine nasal spray v a nicotine patch plus placebo spray for abstinence from smoking*


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.


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 et al point out that nicotine patch treatment alone gives an abstinence rate of only 11% after 1 year. Such results have prompted the search for better single or combination smoking cessation treatments, including combined nicotine patch and spray. Unlike previous studies, Blondal et al followed up patients for an extended period of 6 years. Within the first year, the combination treatment led to a higher abstinence rate than did the patch and placebo spray. Few patients used the spray for up to 1 year. Combination treatment 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 treatment was because of higher sustained concentrations of nicotine or a brief effect on concentration of the spray delivery system. The spray provides a “quick” 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 et al 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 et al was 27%, which is similar to that for bupropion alone (18.4%) or the bupropion patch combination (22.5%) in the study by Jorenby et al. Unlike Blondal et al, Jorenby et al followed up patients for 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 to or as an alternative to, nicotine replacement therapy.

Patients in both studies were highly motivated and received adjunctive supportive counselling. These circumstances may not apply to a larger population of people who smoke and have some desire to stop. Extensive supportive counselling is time consuming, expensive, and difficult to obtain without access to properly trained professionals. The feasibility and success of these treatments in usual ambulatory care settings needs to be determined.

Another important question that has yet to be 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.

It was the connection between mood and smoking that led eventually to the trial of the antidepressant bupropion as a cessation aid. People with negative affect are more likely to start smoking and less likely to give up.2 Affective symptoms are more common among smokers, and their severity is related to the degree of nicotine dependence.3

Although it is unclear how the cessation aids assessed in these 2 studies would perform in a mental health care environment, bupropion could obviously have a dual role among patients with major depression as both an antidepressant and cessation aid. The overall positive effect of cessation aids in the mental healthcare environment may actually be greater than in the general population because smoking is very common among people with psychiatric illness.



  • Sources of funding: Pharmacia and Upjohn.

  • For correspondence: Dr T Blondal, Reykjavik Health Care Centre, Baronstigur 47, 101 Reykjavik, Iceland. Fax +354 562 2415.

  • Abstract and modified commentary also published in ACP Journal Club.

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