REVIEW ARTICLE Smoking Cessation Therapy and the Return of Aviators to Flying Duty
Alon Grossman, Dan-Avi Landau, Erez Barenboim,and Liav Goldstein
GROSSMAN A, LANDAU D-A, BARENBOIM E, GOLDSTEIN L. Smoking
who have experienced a myocardial infarction and con-
cessation therapy and the return of aviators to flying duty. Aviat
tinue to smoke compared with those who quit. Further-
Space Environ Med 2005; 76:1064 –7.
Smoking cessation is an important part of every primary care physi-
more, the risk of a coronary event declines rapidly after
cian’s work. The importance of smoking cessation in the reduction of
smoking cessation, and after 2–3 yr of abstinence, the
cardiovascular morbidity and mortality and the reduction of cancer
risk of such an event is similar to the risk of subjects
incidence cannot be overstated. Various treatments have been estab-
who have never smoked (36). For this reason, the Joint
lished to encourage smoking cessation; these include group and indi-
British Recommendations on Preventing Heart Disease
vidual psychological therapy, nicotine replacement in various forms,and drug therapy. The best-known drug used for smoking cessation is
in Clinical Practice states that smoking cessation is one
bupropion SR (Zyban). Smoking in aviators is not different than in the
of the options for primary lifestyle changes to decrease
general population in terms of prevalence. Thus it is important for flight
the risk of coronary heart disease (34). Coronary heart
surgeons worldwide to be familiar with the magnitude of the problem
disease is particularly important in high-risk occupa-
and the available treatment options. Yet, it is also important for thiscommunity to become familiar with the relevance of this treatment to
tions, such as aviation, where it may lead to premature
aviation and to recognize the limitations pertinent
termination of the aviator’s flying career, which has
who are attempting to quit smoking. We present treatment options for
significant economic as well as psychological implica-
smoking cessations and their limitations on flying personnel.
tions. Despite recent advances, smoking relapse after
Keywords: aviation, aerospace medicine, smoking,
successful intervention for smoking cessation occurs in
70 – 80% of patients within 6 –12 mo (10). Thus in the
flying population it is particularly important to use all
ACH YEAR approximately 20 million of the 50
available treatment options in order to achieve minimal
million smokers in the United States try to quit
relapse rates and to minimize the risk for coronary
smoking, but only 6% of those who try succeed inquitting in the long-term (17). Many effective behav-
ioral and pharmacological therapies are now availablefor the treatment of smoking. The most effective treat-
ment strategy is combined behavioral intervention andpharmacological therapy (1). Effective pharmacological
A recent review published in the Cochrane Database
interventions for smoking cessation include several
summarized the available forms of nicotine replace-
types of nicotine replacement and the use of various
ment therapy and concluded that all the commercially
medications, including bupropion and other antide-
available forms of nicotine replacement therapy (NRTs)
pressants. Aviators are no different from the general
are effective as a part of the effort to promote smoking
population regarding the prevalence of smoking
cessation. They increase quit rates by approximately
(9,11,25,32) and the need for smoking cessation inter-
1.5- to 2-fold regardless of setting. The effectiveness of
vention. In this manuscript we will attempt to present
these agents appears to be largely independent of the
the various treatment options for smoking cessation
intensity of additional support provided to the smoker.
with specific consideration for flying personnel.
Provision of more intense levels of support, althoughbeneficial in facilitating the likelihood of quitting, is notessential to the success of NRT (31). All treatment op-
tions are safe and effective and the choice is a matter of
Strong consistent epidemiological evidence links cig-
arette smoking to increased cardiovascular disease
From the Israeli Air Force Aeromedical Center, Tel Hashomer,
morbidity and mortality. In the developed world, car-
diovascular disease (most often ischemic heart disease)
This manuscript was received for review in May 2005. It was
is the most common smoking-related cause of death
accepted for publication in August 2005.
and 25% of deaths in the 35– 69 age group are believed
Address reprint requests to: Dr. Alon Grossman, Ramon AFB, #10d,
P.O. Ramat Negev, Israel; [email protected].
to be tobacco related (34). It has been recognized that
Reprint & Copyright by Aerospace Medical Association, Alexan-
mortality levels are significantly higher among smokers
Aviation, Space, and Environmental Medicine • Vol. 76, No. 11 • November 2005
SMOKING CESSATION IN AVIATORS—GROSSMAN ET AL.
patient preference, previous experience, and potential
Bupropion: Sustained release bupropion (bupropion
SR) was first launched in the United States in 1997 as an
Nicotine trans-dermal patch: This form of nicotine re-
aid for smoking cessation. Hurt and colleagues (15)
placement improves smoking cessation rates by reduc-
demonstrated that bupropion is an effective smoking
ing withdrawal symptoms and the craving for ciga-
cessation aid: at 12 mo, the abstinence rates were 23%
rettes. Several brands are available either over the
among subjects treated with 300 mg of bupropion per
counter or with prescription. An Agency for Health
day for 7 wk compared with 12% for those assigned to
Care Policy and Research summary of five meta-analy-
receive placebo. Adverse events associated with the
ses found that the nicotine patch at least doubled 6- and
recommended dose of 150 mg twice daily in clinical
12-mo cessation rates relative to placebo-patch compar-
trials most commonly include insomnia, headache, dry
ison groups (37). Skin reactions can occur in up to 20%
mouth, nausea, and anxiety. Only insomnia and dry
of patients (6,17). These reactions are not severe enough
mouth occurred more commonly among those treated
to warrant discontinuation of patch treatment and can
with bupropion compared with those treated with pla-
be ameliorated by the use of medicated creams and by
cebo. No significant changes in BP, heart rate, or routine
laboratory parameters were noted in those treated with
Nicotine gums: The Agency for Health Care Policy and
bupropion SR compared with placebo (3). A rare but
Research Guideline Panel recommends use of the patch
significant side effect of bupropion is seizures. In con-
over gum because of potential problems with adher-
trolled clinical trials of bupropion SR, where smokers
ence to the gum regimen. According to the panel, gum
were carefully screened for risk factors of seizures, the
is likely to be the better choice when patients express apreference for gum, when previous use of the patch has
incidence of seizures was approximately 0.1% (3). In
failed, or when severe reactions occur (such as skin
order to avoid a greater risk smokers should be
irritation) specific to the use of the patch. Nevertheless,
screened for predisposing risk factors and adhere to the
three meta-analyses of the effectiveness of nicotine gum
recommended dose. Another potentially lethal side ef-
found that gum increased 12-mo abstinence rates by
fect of bupropion is a severe hypersensitivity reaction
between 40% and 60% compared with placebo (37).
occurring at a rate of approximately 0.1%. Anecdotal
Nicotine inhaler: This is a plastic device shaped like a
reports of side effects related to bupropion include som-
cigarette that produces a vapor of nicotine when puffed.
nambulism (18), rhabdomyolysis (7), and thrombotic
The advantage of the inhaler is that its shape and man-
thrombocytopenic purpura (21). A study performed
among healthy volunteers in 2002 studying the effects
smoking. It may cause sore throat or coughing, YARPA
on performance found a main effect of bupropion on
“number of awakenings,” “difficulty returning to
found 6-mo abstinence rates between 17% and 28%
sleep,” and “dry mouth.” There was no impact on diz-
compared with 6% and 9% for placebo Thu, 22 Jun 2006 18:16:51
ziness or psychomotor performance (26). The authors
Nicotine nasal spray: The nasal spray provides a dose
concluded in that article that aircrew may be returned
of nicotine much more rapidly than any of the other
to restricted flying duties (in non-fast jet aircraft) under
forms of NRTs, but less rapidly than cigarettes. Some of
close observation once stabilized on bupropion SR.
its side effects include throat irritation, sneezing, cough-
Fluoxetine: A study published in 2004 examined the
ing, and tearing, but these tend to decrease after a week
effect of fluoxetine on smoking cessation in the context
of use. Nasal sprays appear to double quit rates com-
of a program that included a trans-dermal nicotine
pared with placebo (5) and may be particularly effective
patch and group therapy for 6 wk. Fluoxetine did not
significantly improve smoking cessation rates, neither
Combination therapy: Concurrent use of more than one
for patients with a major depressive disorder history
type of NRT may increase abstinence rates. One study
nor for patients without current depression; however,
found that the combination of gum and patch signifi-
the study favored the use of fluoxetine for smoking
cantly increased abstinence rates relative to either
cessation if weight gain was a major clinical obstacle to
method. This combination obtained a 6-mo abstinence
smoking cessation (29). Fluoxetine has both activating
rate of 27.5% and a 12-mo rate of 18.1% (19). The com-
and sedating effects. Activation and sedation were both
bination of nicotine spray with the patch has also been
found to be more common in fluoxetin-treated subjects
evaluated. At 12 mo, the combination spray and patch
than in those treated with placebo, although sedation
treatment resulted in an abstinence rate of 27% com-
was a rare cause for discontinuation of treatment. Se-
pared with a patch-only abstinence rate of 11% (6).
dation usually appeared at the early stages of treatment(4). Both activation and sedation associated with use of
this agent limit its use in aviators.
Antidepressants may have a crucial part in smoking
Nortriptyline: A recent study evaluated the efficacy of
cessation. Depression may be a symptom of nicotine
nortriptyline in smoking cessation (27). There were 160
withdrawal and smoking cessation may sometimes pre-
patients who were randomized to nortriptyline and
cipitate depression. In some individuals, nicotine may
placebo groups with no significant reduction in with-
have antidepressant effects that maintain smoking. The
drawal symptoms. The cessation rate was higher in
most renowned antidepressant used for smoking cessa-
those treated with nortriptyline compared with those
tion is bupropion, but other agents, such as fluoxetine
treated with placebo. Side effects reported with nortrip-
and nortriptyline were evaluated in previous studies.
tyline included dry mouth (38%) and sedation (20%). Aviation, Space, and Environmental Medicine • Vol. 76, No. 11 • November 2005
SMOKING CESSATION IN AVIATORS—GROSSMAN ET AL.
flight simulator testing, specifically on approach tolanding, a task that requires sustained attention (23,24). Clonidine: Clonidine, an antihypertensive drug that
Thus, performance may be compromised not only by
acts on the central nervous system, may reduce with-
withdrawal, but perhaps in part by the elimination of
drawal symptoms in various addictive behaviors, in-
the positive cholinergic effect of nicotine.
cluding tobacco use. There were three trials of oral
These findings emphasize the potential hazards that
treatment and three of transdermal clonidine to evalu-
may accompany abrupt smoking cessation in aviators.
ate the efficacy of this agent for smoking cessation (13).
How effective the different treatment modalities are in
The efficacy of this agent compared with placebo was
eliminating these withdrawal effects is a question that
minimal and side effects, including dry mouth and
remains to be clarified as most available studies have
concentrated on abstinence rates. Jornbey et al. have
Opioid antagonists: Opioid antagonists may attenuate
published a well-designed study of the efficacy of NRT
the rewarding effects of cigarette smoking and thus
and buproprion for smoking cessation (17). They have
may aid smoking cessation. Two trials of naltrexone
showed a significant reduction, though not elimination,
were conducted in this field and both failed to detect a
of withdrawal symptoms with NRT, buproprion, and a
significant difference in quit rates between naltrexone
combination of both. Other studies have demonstrated
a similar effect to a lesser degree (15,35), and conflictingresults regarding depressive symptoms (2,15). Thus it
appears that although pharmacotherapy may some-what reduce withdrawal symptoms, performance un-
Urging aviators to quit smoking is a major task for
der these circumstances warrants further study.
every aeromedical examiner. Aside from its known haz-
Another important issue to consider is that the vari-
ards, smoking may lead to flight career termination in
ous drug treatments available for smoking cessation are
aviators due to a myriad of reasons. The major question
all associated with side effects, which may lead to in-
is the timing of return to flying duty following smoking
flight incapacitation. Nortriptyline is associated with
sedation and thus is not allowed for use in aviators. The
Nicotine withdrawal may lead to various symptoms
same holds true for clonidine. Fluoxetine may be asso-
among aviators, potentially leading to decreased per-
ciated with sedation to a lesser extent, but its efficacy is
formance. Nicotine withdrawal has several effects on
limited. Bupropion has been established as the most
effective smoking cessation aid available. However, it is
lescents found that smoking cessation in this
associated with sleep disturbances, and more impor-
tion was associated with impairments of verbal mem-
tantly may precipitate seizures that, although extremely
rare, may prove lethal during flight. A seizure rate of
decrements in cognitive performance Thu, 22 Jun 2006 18:16:51
0.1%, which is higher then that found in the general
tional study found that in subjects deprived of ciga-
population, was found in pre-screened subjects. Addi-
rettes for 24 h, there were significant effects on cognitive
tionally, the effect of environmental exposures related
performance which included increased mean reaction
to flying, such as hypoxia and high Gz, has not been
time, increased variability in reaction time, and in-
studied in treated subjects. The great importance of
creased errors of commission on vigilance tasks (14). A
smoking cessation makes it crucial to use all available
study performed in 20 aviators operating various air-
options for achieving this goal. Yet, withdrawal symp-
crafts who were subjected to 12-h abstinence from cig-
toms and side effects mentioned should lead to caution
arette smoking was reported in 2003 (12). The most
regarding use of this treatment in aviators, particularly
frequent symptoms reported during nicotine depriva-
in the immediate period following smoking cessation.
tion were nervousness, craving for tobacco, tension-anxiety, fatigue, difficulty in concentration, decrease in
alertness, disorders of fine adjustments, prolonged re-action times, anger-irritability, drowsiness, increase in
Smoking cessation should be strongly encouraged in
appetite, and impairment of judgment. Tests performed
aviators and all available means should be used to
during flight recorded an impairment of cognitive func-
promote cessation and abstinence. We believe that in
the immediate period following quitting, aviators
A previous publication in this journal reviewed the
should be grounded. We believe that the minimal pe-
clinical effects of nicotine withdrawal (33). These in-
riod required before return to the cockpit should be
clude a decrease in digit recall, serial addition subtrac-
approximately 1–2 wk, depending on the clinical man-
tion, and job satisfaction. Aggressiveness, confusion,
ifestations. Because nicotine withdrawal impairs judg-
and impulsivity are also increased on withdrawal (33).
ment, which is a crucial element required for flight, we
Furthermore, several studies have investigated the ef-
think that this rule should apply to both single-seat and
fects of cholinergic agents, such as nicotine, on perfor-
multi-crew platforms. We believe use of NRTs should
mance. Among those, human studies have demon-
be allowed in aviators, as these agents have minimal
strated improved attention, information processing,
side effects, and in fact minimize the symptoms which
and memory functions in patients with Alzheimer’s
may be hazardous to flight. Yet, we think that the
and Parkinson’s disease (28), as well as in healthy non-
various systemic agents should not be allowed for use
smoking volunteers (22). A beneficial effect of cholin-
in aviators while flying, as side effects from these treat-
ergic agents have also been demonstrated in pilots in
ments may prove fatal in the cockpit. Aviation, Space, and Environmental Medicine • Vol. 76, No. 11 • November 2005
SMOKING CESSATION IN AVIATORS—GROSSMAN ET AL.
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