Sequential Use of Fluoxetine for Smokers With Elevated Depressive Symptoms

• Sponsor: Butler Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT00578669
• Collaborator: National Institute on Drug Abuse (NIDA) (NIH)
• Enrollment: 206
• Location: 1
• Arms: 2
• Duration (Months): 67
• Patients Per Site Per Month: 3.1

Study Details

Study Description

Brief Summary

The primary purpose of this study is to determine whether, among smokers with elevated depressive symptoms, sequential antidepressant pharmacotherapy with fluoxetine (20 mg) begun 8 weeks prior to and extended throughout standard smoking cessation treatment with transdermal nicotine patch (ST-TNP) will result in superior short-and long-term smoking cessation outcomes compared to sequential pharmacotherapy with placebo medication combined with ST-TNP. The secondary aim of the study is to test the hypothesis that, among smokers with elevated depressive symptoms, sequential treatment with fluoxetine will result in lower levels of depressive symptoms and negative mood and higher levels of positive mood immediately prior to and throughout the course of smoking cessation treatment relative to the placebo condition.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder; Nicotine Dependence; Depression	Drug: Fluoxetine; Drug: Dextrose	Phase 3

Detailed Description

Cigarette smoking is the leading cause of death and disability in the United States, accounting for over 430,000 deaths in this country every year. The selection hypothesis of smoking prevalence argues that smokers who are unable to quit successfully are likely to possess risk factors or characteristics that make it difficult to quit, such as nicotine dependence and psychiatric comorbidity. As such, significant strides in helping "today's" smokers quit will ultimately be found in the ability to develop specialized treatments that target the particular needs of subgroups of smokers, especially those who are at higher risk for relapse. Depression is the psychiatric disorder most frequently associated with cigarette smoking in adults and strong associations have been demonstrated between cigarette smoking and both depressive disorders and depressive symptoms. In fact, a prospective analysis from the National Health and Nutrition Examination Survey showed that smokers with elevated depressive symptoms were 40% less likely than nondepressed smokers to have quit nine years later.

The development of an efficacious, specialized treatment of nicotine dependence for smokers with elevated depressive symptoms would address this need by providing physicians with an effective treatment alternative for the large number of smokers with depressive symptoms seen daily in clinical practice. This study examines the hypothesis that smokers with elevated depressive symptoms treated with fluoxetine 8 weeks prior to quitting and extended throughout 8 weeks of standard treatment with the nicotine patch post-quit will demonstrate superior cessation outcomes compared to placebo medication combined with standard treatment and the nicotine patch, administered with the identical treatment schedule. A secondary hypothesis is to examine whether reductions in depressive symptoms and negative mood and increases in positive mood will be greater for those in the sequential fluoxetine versus placebo condition.

Study Design

• Study Type: Interventional
• Actual Enrollment: 206 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Sequential Use of Fluoxetine for Smokers With Elevated Depressive Symptoms
• Study Start Date: Apr 1, 2008
• Actual Primary Completion Date: Jul 1, 2013
• Actual Study Completion Date: Nov 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1 Sequential antidepressant pharmacotherapy with (20mg) fluoxetine, begun 8 weeks prior to and extended throughout brief (behavioral) standard smoking cessation treatment with transdermal nicotine patch.	Drug: Fluoxetine; 20mg once daily for 16 weeks; Other Names: Prozac
Placebo Comparator: 2 Sequential placebo medication (dextrose), begun 8 weeks prior to and extended throughout brief (behavioral) standard smoking cessation treatment with transdermal nicotine patch.	Drug: Dextrose; Once daily for 16 weeks

Outcome Measures

Primary Outcome Measures

1. Number of Participants Achieving Smoking Abstinence [One year]

   7-day point prevalence abstinence

Secondary Outcome Measures

1. Self-reported Depressive Symptoms [One year]

   Self-reported depressive symptoms based on the Center for Epidemiologic Studies-Depression (CES-D) scale. CES-D consists of 20 items, with total scores on the scale ranging from 0 - 60. Higher scores are indicative of greater levels of depressive symptoms.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Regular smoker for at least one year

• Currently smokes at least 10 cigarettes per day

• Elevated depressive symptoms

• Uses no other tobacco products

Exclusion Criteria:

• Current Axis I disorder, including Major Depressive Disorder

• Psychoactive substance abuse or dependence (excluding nicotine dependence) within past year

• Current use of psychotropic medication

• Use of antidepressant medication within past 6 months

• Current suicidal risk

• History of significant medical illness, such as cardiovascular disease, neurological, gastrointestinal, or other systemic illness

• Pregnancy or breast feeding

• Use of nicotine replacement therapy or of any medication for smoking cessation not provided by the researchers during the quit attempt

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Butler Hospital	Providence	Rhode Island	United States	02906

Sponsors and Collaborators

• Butler Hospital
• National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: Richard A. Brown, Ph.D., Butler Hospital

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Website for Butler Hospital with links to research

Publications

None provided.

• Responsible Party: Butler Hospital
• ClinicalTrials.gov Identifier: NCT00578669
• Other Study ID Numbers: PHI0710-002; 1R01DA023190
• First Posted: Dec 21, 2007
• Last Update Posted: Oct 16, 2018
• Last Verified: Sep 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Butler Hospital: Smoking Cessation; Tobacco Use Cessation; Antidepressants
• Additional relevant MeSH terms: Tobacco Use Disorder; Depression; Depressive Disorder; Depressive Disorder, Major; Fluoxetine

Study Results

Participant Flow

Arm/Group Title	Sequential Fluoxetine	Sequential Placebo
Arm/Group Description	Sequential Fluoxetine - Participants received sequential antidepressant pharmacotherapy (fluoxetine - 20 mg.) that was begun 8 weeks prior to, and extended throughout the treatment phase. The treatment phase consisted of 8 weeks of brief behavioral counseling and transdermal nicotine patches. Fluoxetine was used once daily for 16 weeks.	Sequential placebo medication (dextrose), begun 8 weeks prior to and extended throughout the 8-week brief (behavioral) standard smoking cessation treatment with transdermal nicotine patch. Dextrose was used once daily for 16 weeks
Period Title: Overall Study
STARTED	107	99
COMPLETED	107	99
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Sequential Placebo	Sequential Fluoxetine	Total
Arm/Group Description	Participants received placebo medication, dextrose, that was begun 8 weeks prior to and extended throughout the brief, behavioral standard smoking cessation treatment that included transdermal nicotine patch. The placebo medication (dextrose) was taken once daily for 16 weeks.	Participants received fluoxetine medication, 20 mg, that was begun 8 weeks prior to and extended throughout the brief, behavioral standard smoking cessation treatment that included transdermal nicotine patch. The fluoxetine medication (20 mg) was taken once daily for 16 weeks.	Total of all reporting groups
Overall Participants	99	107	206
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44.05 (11.40)	43.07 (10.97)	43.54 (11.16)
Sex: Female, Male (Count of Participants)
Female	48 48.5%	51 47.7%	99 48.1%
Male	51 51.5%	56 52.3%	107 51.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 1%	2 1.9%	3 1.5%
Not Hispanic or Latino	98 99%	105 98.1%	203 98.5%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	4 4%	0 0%	4 1.9%
Asian	0 0%	2 1.9%	2 1%
Native Hawaiian or Other Pacific Islander	1 1%	0 0%	1 0.5%
Black or African American	5 5.1%	6 5.6%	11 5.3%
White	89 89.9%	99 92.5%	188 91.3%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	99 100%	107 100%	206 100%
Cigarettes smoked per day (past month) (cigarettes) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cigarettes]	21.07 (9.03)	20.96 (10.33)	21.01 (9.7)
Fagerstrom Test for Nicotine Dependence (FTND) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	5.40 (2.37)	5.90 (1.74)	5.66 (2.08)
Center for Epidemiologic Studies - Depression (CES-D) scale (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	9.64 (8.53)	9.90 (8.14)	9.77 (8.31)
Center for Epidemiologic Studies - Depression (CES-D) > 16 (Count of Participants)
Count of Participants [Participants]	15 15.2%	21 19.6%	36 17.5%
Recurrent major depressive disorder (MDD) (Count of Participants)
Count of Participants [Participants]	18 18.2%	16 15%	34 16.5%
Single major depressive disorder (MDD) episode (Count of Participants)
Count of Participants [Participants]	7 7.1%	7 6.5%	14 6.8%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Achieving Smoking Abstinence
Description	7-day point prevalence abstinence
Time Frame	One year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sequential Fluoxetine	Sequential Placebo
Arm/Group Description	Sequential Fluoxetine - Participants received sequential antidepressant pharmacotherapy (fluoxetine - 20 mg.) that was begun 8 weeks prior to, and extended throughout the treatment phase. The treatment phase consisted of 8 weeks of brief behavioral counseling and transdermal nicotine patches. Fluoxetine was used once daily for 16 weeks.	Sequential placebo medication (dextrose), begun 8 weeks prior to and extended throughout the 8-week brief (behavioral) standard smoking cessation treatment with transdermal nicotine patch. Dextrose was used once daily for 16 weeks
Measure Participants	107	99
Count of Participants [Participants]	24 24.2%	18 16.8%

2. Secondary Outcome

Title	Self-reported Depressive Symptoms
Description	Self-reported depressive symptoms based on the Center for Epidemiologic Studies-Depression (CES-D) scale. CES-D consists of 20 items, with total scores on the scale ranging from 0 - 60. Higher scores are indicative of greater levels of depressive symptoms.
Time Frame	One year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sequential Fluoxetine	Sequential Placebo
Arm/Group Description	Sequential Fluoxetine - Participants received sequential antidepressant pharmacotherapy (fluoxetine - 20 mg.) that was begun 8 weeks prior to, and extended throughout the treatment phase. The treatment phase consisted of 8 weeks of brief behavioral counseling and transdermal nicotine patches. Fluoxetine was used once daily for 16 weeks.	Sequential placebo medication (dextrose), begun 8 weeks prior to and extended throughout the 8-week brief (behavioral) standard smoking cessation treatment with transdermal nicotine patch. Dextrose was used once daily for 16 weeks
Measure Participants	107	99
Mean (Standard Deviation) [score on a scale]	9.9 (8.14)	9.64 (8.53)

Adverse Events

Time Frame	Adverse event data were collected over a one year period.
Adverse Event Reporting Description	Definitions of adverse event and/or serious adverse event do not differ from the clinicaltrials.gov definitions.
Arm/Group Title	Sequential Fluoxetine		Sequential Placebo
Arm/Group Description	Sequential antidepressant pharmacotherapy with (20mg) fluoxetine, begun 8 weeks prior to and extended throughout brief (behavioral) standard smoking cessation treatment with transdermal nicotine patch. Fluoxetine: 20mg once daily for 16 weeks		Sequential placebo medication (dextrose), begun 8 weeks prior to and extended throughout brief (behavioral) standard smoking cessation treatment with transdermal nicotine patch. Dextrose: Once daily for 16 weeks
All Cause Mortality
	Sequential Fluoxetine		Sequential Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/107 (0%)		0/99 (0%)
Serious Adverse Events
	Sequential Fluoxetine		Sequential Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/107 (0%)		0/99 (0%)
Other (Not Including Serious) Adverse Events
	Sequential Fluoxetine		Sequential Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/107 (0.9%)		0/99 (0%)
Gastrointestinal disorders
Frequent bowel movements	1/107 (0.9%)	1	0/99 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.