Treatments for Tobacco addiction:
I. Nicotine replacement therapies
- Transdermal nicotine
- Nicotine gum: start with one 2mg piece per day for every 2
cigarettes previously smoked; for pts who smoke > 1 PPD or
have Fagerstrom scores > 6, one 4mg piece for every 3-4
cigarettes previously smoked. Chew a couple of times then keep
between cheek and gum. Chew a couple of times once a min for
15-30min per dose. Avoid while using beverages.
- Nicotine nasal spray: Use 1 spray in each nostril at a time.
Can use 8-10 doses/day initially; taper after 6wks. Can cause
some rhinorrhea, sneezing, and nasal irritation but that
decreases after 1 wk; use along with the patch may increase
long-term cessation rates (BMJ 318:285, 1999--JW)
- Bupropion as sole pharmacologic treatment for tobacco addiction
- 615 nondepressed adult smokers w/o history of sz
randomized to buproprion 100, 150, or 300mg/d vs.
placebox 7wks. At 7wks, success rates at quitting were
38.6% at 300/d vs. 19% with placebo (other doses
intermediate); at 12mos, quit rates were 23.1% at 300/d
vs. 12.4% in placebo group (sig.) (NEJM 337:1195,
- 893 pts > 18yo smoking > 14 cigarettes/day
randomized to bupropion 150mg BID, nicotine patch, both, or double
placebo, x 9wks. At 12mos, smoking prevalence was 84.4% in placebo group,
83.6% in nicotine group, 69.7% in bupropion-only group, and 64.5% in
combined-therapy group (NEJM 340:685, 1999--AFP)
- However, in a randomized trial in 429 smokers abstinent x 7wks on
Bupropion, adding an additional 45wks of bupropion (vs. placebo) was ass'd
with sig. increased abstinence rates at the end of tx (55% vs. 42%);
however, abstinence rates were identical 1y after tx ended (Ann. Int. Med.
- Bupropion as adjunctive therapy to nicotine replacement
- In a randomized study of 243 smokers randomized to bupropion 150mg
BID vs. placebo; all also received nicotine replacement. No sig.
diff. in 1y quit rates between the two groups (Arch. Int. Med.
- Risk of sz at 300 QD is about 0.1%; higher if other risks
for sz are plresent, e.g. EtOH withdrawal or use of
- Side f/x include agitation, insomnia, tremor, HA, and dry
- Don't combine w/MAOIs or ritonavir and avoid concurrent
SSRI's (reprts of panic and/or psychosis when used in
- Recc'd dose is 150 QD x 3d then BID x 7-12wks. OK to
combine w/nicotine replacement. Quit during 2nd wk of tx.
III. Tricyclic Antidepressants
- 144 non-depressed smokers 18-65yo randomized to nortriptyline 75mg/d vs.
placebo; all also participated in group behavioral treatment. At 6mos,
cessation rate was sig. greater in nortriptyline group (20.6% vs. 5.3%)
(Chest 122:403, 2002--AFP)
IV. Varenicline (Chantix)
Partial agonist of
the an alpha-4-beta-2-nicotonic receptor,
which produces the reinforcing effects of nicotine.\
Reduces physiologic component of nicotine withdrawal
and also blocks exogenous nicotine from reinforcing effects e.g. euphoria.
1mg BID x 12wks
If abstinent @ 12wks can be continued on
varenicline for an additional 12 wks (doing so is associated with higher
1y quit rates)
Nausea is reduced if the dose of varenicline is
titrated upward over one week, from 0.5 mg daily for three days to 0.5
mg twice daily for four days, and then 1 mg twice daily for the
remainder of a 12-week course
Instruct patient to quit one week after starting
Excretion is almost entirely renal; dosage
adjustment recommended in patients with renal insufficiency
Nausea (about 30% of patients, usually mild; can
be minimized by taking varenicline with food and a full glass of water)
Abnormal dreams (about 10% of patients).
Case reports exist in patients being
treated with varenicline of depressed mood, suicidal thoughts,
aggressive and erratic behavior, and agitation, but these have
not been observed at a higher rate with varenicline compared with
placebo in clinical trials. Other reported side f/x include vision
disturbances, syncope, and moderate and severe skin reactions.
Also, case reports of accidental injuries from MVAs and and falls.
Precautions re: side f/x:
Advise pt of potential impairment of ability
to drive or operate heavy machinery
Take psychiatric history prior starting and
consider avoiding if h/o suicidal ideation, current unstable
psychiatric status, or current major depression.
Advise re: potential of nausea, abnormal
dreams, and neuropsychiatric side f/x
- Clinical trials:
- In a study in 638 smokers 18-65yo randomized to varenicline, bupropion, or
placebo x 7wks, varenicline goup had sig. greater quit rates at 4wks (48%
vs. 33% for bupropion and 17% with placebo) and 1y (14% for varenicline and
5% for placebo; summary didn't give data for bupropion) (Arch. Int.
Med. 166:1553, 2006--JW)
- In a study in 1,025 generally healthy smokers 18-75yo randomized to
varenicline 1mg BID, bupropion SR 150mg BID, or placebo x 12wks, at 52wks,
abstinence rates were 21.9% in the varenicline group vs. 16.1% with
bupropion and 8.4% with placebo. The varenicline-placebo diff. was
significant but the varenicline-bupropion diff. was not. 28% of
varenicline recipients experienced nausea (JAMA 296:47, 2006--abst)
- In a study in 1,027 adults smokers randomized to varenicline 1mg BID,
bupropion SR 150mg BID, vs. placebo x 12wks, at 52wks, abstinence rates were
23% in the varenicline group vs. 14.6% with bupropion and 10.3% with
placebo. Both the varenicline-placebo and varenicline-bupropion diffs.
were sig. 29% of varenicline recipients experienced nausea (JAMA
- In a study in 1,,210 adults smokers who had been abstinent for at least
1wk at the end of a 12wk course of open-label varenicline 1mg BID,
randomized to continued varenicline 1mg BID vs. placebo x 12 additional
weeks, at 52wks, the varenicline group had sig. higher abstinence rates
(43.6% vs. 36.9%) (JAMA 296:64, 2006--abst)
V. Comparisons among treatments for tobacco dependence
In a study in 1,504 adult smokers randomized to one
of the following regimens for smoking cessation x 8wks:
The combination of patches + lozenges was associated
with sig. longer duration of tobacco abstinence than pts in the other groups
(Arch. Gen. Psychiat. 66:1253, 2009-FP News 11/15/09)
"Fagerstrom" test for nicotine dependence:
I. How soon after you wake up do you smoke your first
- 5 min or less: 3
- 6-30min: 2
- 31-60min: 1
- >60min: 0
II. Do you find it difficult to refrain from smoking in places
where it is forbidden (e.g. in church, at the library, in a
- Yes 1
- No 0
III. Which cigarette in the day would you hate most to give
- The first in the morning 1
- Any other 0
IV. How many cigarettes per day do you smoke?
- 10 or less 0
- 11-20 1
- 21-30 2
- >31 3
V. Do you smoke more frequently during the first hours after
waking than during the rest of the day?
- Yes 1
- No 0
VI. Do you smoke if you are so ill that you are in bed most of
- Yes 1
- No 0
Scores of > 6 are generally interpreted as indicating a
high degree of dependence, with more severe withdrawal sx,
greater difficulty in quitting and benefit from nicotine
replacement (Br. J. Addict 86:1119, 1991)