Effect of Paroxetine on Smokers' Cardiovascular Response to Stress - 1

Smokers report that they often smoke cigarettes during stressful times. Smoking and stress
produce similar physiological responses such as increases in heart rate, blood pressure, and
adrenaline levels. The combination of smoking and stress results in greater increases in
these physiological responses compared to smoking or stress alone. Such increases are
thought to be harmful to cardiovascular health. Additionally, smokers with exaggerated
responses to stress may be more likely to relapse following a smoking cessation attempt. The
purpose of this study is to assess the effects of paroxetine, a selective serotonin reuptake
inhibitor (SSRI), on the cardiovascular response to stress after smoking.

Participants in this double-blind, placebo-controlled study will receive 1 month of
paroxetine and 1 month of placebo with the order of which is taken during the first month
randomly assigned. Paroxetine will be administered at a daily dose of 10 mg for the first
week and increased to a daily dose of 20 mg for the remainder of the study. After one month
of medication, participants will abstain from smoking for one night and then undergo mental
stress testing the following day. Immediately prior to the mental stress testing,
participants will smoke a cigarette. Mental stressors will include speaking and math tasks.
Physiological measures of stress (e.g., blood pressure, heart rate, and plasma catecholamine
concentrations) and subjective measures of stress will be evaluated. Following the second
month of medication, participants will again undergo the procedure for mental stress testing
and evaluation.

Inclusion Criteria:

- Smokes an average of at least 10 cigarettes per day during the year prior to
enrollment

Exclusion Criteria:

- Interested in quitting smoking within the 3 months following enrollment

- Current unstable medical condition

- Substance abuse within the year prior to enrollment

- Current use of any medications (e.g., psychoactive medications, antihypertensives)
that, in the opinion of the investigators, might interfere with study measures or
that would be expected to interact with paroxetine (e.g., CYP2D6 substrates)

- Smoking cessation therapy within the 3 months prior to enrollment

- Regular use of any form of tobacco other than cigarettes

- Significant psychiatric disorders as assessed by the PRIME-MD and verified by a
clinician

- History of hypersensitivity to any selective serotonin reuptake inhibitor

- Pregnancy or breastfeeding