Adaptive Pharmacotherapy for Smoking Cessation

The purpose of this study is to assess an "adaptive" approach to smoking cessation
pharmacotherapy. The protocol is designed to compare adaptive vs. standard approaches to two
common smoking cessation pharmacotherapies (Varenicline and Nicotine Patch). The adaptive
treatment approach provides the addition of Bupropion in the pre-quit period for participants
who are not "responding" to initial treatment. Little is known about the adaptive use of
Varenicline or Nicotine Patch, in which Bupropion is added to Varenicline or Patch for those
who do not respond to one of these medications in a pre-quit treatment period. This study
attempts to address these knowledge deficits. The study (N=300) is a double-blinded
randomized placebo-controlled trial designed to compare biochemically-confirmed abstinence
rates in smokers randomized to Varenicline Adaptive Protocol vs. Varenicline (N=150) and for
comparison, Nicotine Patch Adaptive Protocol vs. Nicotine Patch (N=150). The "Varenicline
Adaptive Protocol" is conducted by starting treatment with Varenicline 4 weeks prior to the
quit day and following each participant's response to this pre-treatment medication. After 2
weeks, if the patient shows a reduction greater than 50% in cigarettes smoked per day, then
the patient is considered to be a "Varenicline responder" and is continued on Varenicline
alone out to 12-weeks post quit day. If the patient does not spontaneously decrease smoking
in the pre-quit period by more than 50% cigarettes per day, the patient is considered to be a
"Varenicline non-responder" and Bupropion is added to the Varenicline. For comparison, an
identical protocol is used with nicotine patch vs. nicotine patch adaptive treatment. The
study uses only FDA-approved medications: Varenicline, Nicotine Patch, Bupropion, and placebo
controls. To pattern clinical practice, participants will be able to choose whether they
would like to use a patch or Varenicline-based treatment. After choosing, however, they will
be randomized to adaptive vs. non-adaptive version of that treatment. Placebo medications are
matched throughout the study. Participants will be blinded to all medications. All
participants will receive behavioral treatment including a single 40-minute visit with a
medical provider. The study is designed to provide researchers and clinicians with a better
understanding of how to use adaptive pharmacotherapy protocols to improve smoking cessation
rates.

Inclusion Criteria

1. Age 18 years or older

2. Actively smoking 5 or more cigarettes per day for at least one year

3. Fluency in spoken and written English

4. Willing to set a quit date within 6 weeks

5. Access to a telephone

6. Willingness to take Varenicline OR nicotine patch (patient choice)

7. Willingness to take Bupropion

Exclusion Criteria

1. Daily use of a second form of tobacco or nicotine (e.g. e-cigarettes, cigars, chewing
tobacco, snuff).

2. Current use of a smoking cessation medication (e.g. nicotine replacement, Varenicline,
Bupropion).

3. Report of pregnancy, attempting to get pregnant, or actively breast feeding or
positive urine pregnancy test (only given to females with child bearing potential).

4. Additional criteria may apply.