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

Smoking, Antidepressants, and Response to Mental Stress

Smokers report that they often smoke cigarettes during stressful times. The combined effect of smoking and exposure to stress leads to exaggerated increases in blood pressure, heart rate and other measures of stress response. This combination may result in greater cardiovascular harm than either smoking or stress alone. The purpose of this study is to determine the effects of paroxetine on the response to stress after smoking.

Study Overview

• Status: Completed
• Conditions: Tobacco Use Disorder
• Intervention / Treatment: Drug: Placebo; Drug: Paroxetine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 105
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • College of Pharmacy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Active medication for 4 weeks followed by placebo for 4 weeks	Drug: Placebo; Drug: Paroxetine; 10 mg for 1 week followed by 20 mg for 3 weeks
Experimental: 2; Placebo for 4 weeks followed by active for 4 weeks	Drug: Placebo; Drug: Paroxetine; 10 mg for 1 week followed by 20 mg for 3 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Systolic Blood Pressure Response to Stress	Change in systolic blood pressure from Resting period to that observed during a speech delivered immediately after smoking a cigarette	After 4 weeks of paroxetine / placebo

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diastolic Blood Pressure Response to Stress	Change in diastolic blood pressure from Resting period to that observed during a speech delivered immediately after smoking a cigarette	After 4 weeks of paroxetine / placebo
Heart Rate Response to Stress	Change in heart rate from Resting period to that observed during a speech delivered immediately after smoking a cigarette	After 4 weeks of paroxetine / placebo
Plasma Epinephrine Concentration Response to Stress	Change in plasma epinephrine concentrations from Resting period to those observed during a speech delivered immediately after smoking a cigarette	After 4 weeks of paroxetine / placebo
Plasma Norepinephrine Concentration Response to Stress	Change in plasma norepinephrine concentrations from Resting period to those observed during a speech delivered immediately after smoking a cigarette	After 4 weeks of paroxetine / placebo

Collaborators and Investigators

• Sponsor: University of Minnesota
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Michael Kotlyar, University of Minnesota

Publications and helpful links

General Publications

• Kotlyar M, al'Absi M, Thuras P, Vuchetich JP, Adson DE, Nowack AL, Hatsukami DK. Effect of paroxetine on physiological response to stress and smoking. Psychosom Med. 2013 Apr;75(3):236-43. doi: 10.1097/PSY.0b013e3182898f6d. Epub 2013 Mar 15.

Study record dates

Study Major Dates

• Study Start: October 1, 2005
• Primary Completion (Actual): August 1, 2010
• Study Completion (Actual): August 1, 2010

Study Registration Dates

• First Submitted: September 16, 2005
• First Submitted That Met QC Criteria: September 16, 2005
• First Posted (Estimate): September 22, 2005

Study Record Updates

• Last Update Posted (Actual): November 1, 2019
• Last Update Submitted That Met QC Criteria: October 30, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Smoking
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Tobacco Use Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6 Inhibitors; Paroxetine
• Other Study ID Numbers: 0310M52790; DPMC (Other Identifier: NIDA); K23DA017307-01 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No