Varenicline in Bipolar Depressed Patients

• Sponsor: Mark Frye (Other)
• Overall Status: Completed
• CT.gov ID: NCT00813800
• Collaborator: Pfizer (Industry)
• Enrollment: 11
• Location: 1
• Arm: 1
• Duration (Months): 25
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

Patients with bipolar disorder have one of the highest rates of nicotine dependence and one of the lowest quit rates. Varenicline has been shown in previous trials to be effective for smoking cessation, but has not been studied in subjects with bipolar disorder. This 12-week open label trial will be conducted to assess the feasibility, acceptability, and safety of varenicline in bipolar depressed smokers, given in addition to the subject's primary treatment for bipolar disorder. The primary study hypothesis was that the abstinence rate for bipolar depressed patients will be 50%.

Condition or Disease	Intervention/Treatment	Phase
Smoking; Bipolar Disorder; Depression	Drug: Varenicline	N/A

Detailed Description

Varenicline, a nicotinic acetylcholine receptor partial agonist, has been shown in two placebo-controlled trials to be efficacious for smoking cessation. Given the high prevalence of nicotine dependence in bipolar disorder and the high prevalence of sub-syndromal and syndromal depressive symptoms in bipolar disorder, this 12-week adjunctive varenicline open label trial will be conducted to assess the feasibility, acceptability, and safety of varenicline in bipolar depressed smokers. All subjects will receive individual behavioral counseling.

Primary hypothesis: the abstinence rate for bipolar depressed patients will be 50%. Secondary hypothesis: At final visit, bipolar depressed patients who have achieved remission, defined as a Montgomery Asberg Depression Rating Scale (MADRS) <8, will have a higher rate of tobacco abstinence than depressed patients who did not achieve remission (MADRS >/= 8).

Study Design

• Study Type: Interventional
• Actual Enrollment: 11 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Varenicline for Smoking Cessation in Bipolar Depressed Patients: An Open-Label 12-week Feasibility Trial
• Study Start Date: Jan 1, 2009
• Actual Primary Completion Date: Jan 1, 2011
• Actual Study Completion Date: Feb 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Varenicline Open-label; subjects will receive a behavioral intervention in addition to Varenicline.	Drug: Varenicline; Varenicline (Chantix®, Pfizer) is an oral medication with a recommended dosage of 0.5 mg once daily for 3 days, increasing to 0.5 mg twice daily for days 4-7, and then to the maintenance dose of 1 mg twice daily for the 12 weeks of treatment.; Other Names: Chantix

Outcome Measures

Primary Outcome Measures

1. Carbon Monoxide Breath Level at 12 Weeks [12 weeks]

   Measured by expired breath in parts per million (ppm)

Secondary Outcome Measures

1. Montgomery-Asberg Depression Rating Scale (MADRS) at 12 Weeks [12 weeks]

   MADRS is a ten-item diagnostic questionnaire which psychiatrists use to measure the severity of depressive episodes in patients with mood disorders. Each item on the MADRS is scaled 0 through 6. Lowest score = 0, would indicate no depressive symptoms. Highest score = 60, indicating extreme depression. MADRS score > 20 is syndromal depression. Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry 1979; 134:382-389.

2. Young Mania Rating Scale (YMRS) at 12 Weeks [12 weeks]

   YMRS is an eleven-item, multiple choice diagnostic questionnaire which psychiatrists use to measure the severity of manic episodes in patients already diagnosed with mania. Lowest score = 0, normal subject; Highest score = 60, highly manic subject. For this scale the following scores are associated with these grades of severity: mania (YMRS = 20), hypomania (YMRS = 12), under 5 is classified as non-manic. Young RC, Biggs JT, Ziegler Ve, Meyer DA. A rating scale for mania: reliability, validity and sensitivity. BR J Psychiatry 1978; 133:429-435.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age 18 -65 years

• Meet DSM-IV criteria for bipolar disorder type I or II and nicotine dependence

• DSM-IV confirmed current major depressive episode OR current depressive symptoms defined as MADRS > 4 & <20

• Smoke at least 10 cigarettes per day

• Fagerström Test of Nicotine Dependence (FTND) score of 5 or higher

• Agree to identify collateral individuals for contact purposes to facilitate follow-up appointments

• Currently on mood stabilization treatment. A minimum daily therapeutic dosage of at least one mood stabilizer, and on the same dose for at least 2 weeks:

• Lithium (0.6-1.2 mEq/L or 900 mg), Valproate (50-125 mg/mL or 1000 mg), Carbamazepine (4-12 mg/mL or 800 mg), Oxcarbazepine 1200 mg, Lamotrigine 100 mg, Olanzapine 10mg, Risperidone 2mg, Quetiapine 300mg, Ziprasidone 40mg, Aripiprazole 7.5 mg

• Antidepressants are not exclusionary.

• Topiramate is an acceptable mood stabilization treatment. There is an evidence base (Delbello et al. 2005) highlighting efficacy of topiramate monotherapy for acute mania in children and adolescents with bipolar disorder type 1.

[Mood stabilizers are a standard American Psychiatric Association (APA) treatment guidelines for Bipolar I disorder (history of mania). While the guidelines for Bipolar II disorder are unclear (history of hypomania), we feel mood stabilization provides standardization of treatment and maximizes safety (ie: preventing switch from depression to mania or hypomania).]

Exclusion Criteria:

• DSM-IV dependence for a substance other than nicotine or caffeine within past 3 months.

• DSM-IV criteria of schizophrenia or other non-affective psychotic disorder

• Psychotic symptoms within the past month

• Active suicidality as measured by screening questions from the Columbia-Suicide Severity Rating Scale (C-SSRS

• History of medically serious suicide attempt as reviewed by doctor.

• Current use (past 30 days) of other smoking cessation treatments

• Pregnant or nursing women, or women who refuse to use adequate birth control

• Serious, active or unstable medical condition

• Individuals, in the investigators opinion, unable to comply with study procedures

• Inability to provide written informed consent in English

• Allergic reaction to varenicline

• Individuals who are on dialysis or have a history of kidney disease (varenicline is excreted 96% unchanged through the kidneys) or Creatine supplementation or current anticipated daily NSAID use

• Presence of a personality disorder, that upon review of the medical record, appears to be the primary reason for psychiatric care.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

• Mark Frye
• Pfizer

Investigators

• Principal Investigator: Mark A. Frye, M.D., Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Mayo Clinic Clinical Trials

Publications

None provided.

• Responsible Party: Mark Frye, MD, Professor of Psychiatry, College of Medicine, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT00813800
• Other Study ID Numbers: 08-003471
• First Posted: Dec 23, 2008
• Last Update Posted: Jan 30, 2012
• Last Verified: Dec 1, 2011

• Keywords provided by Mark Frye, MD, Professor of Psychiatry, College of Medicine, Mayo Clinic: Smoking; Bipolar Disorder; Depression
• Additional relevant MeSH terms: Depression; Bipolar Disorder; Varenicline

Study Results

Participant Flow

Recruitment Details	11 patients were enrolled from the community all with bipolar depression and the desire to stop smoking.
Pre-assignment Detail	36 patients who were screened did not meet inclusion/exclusion criteria and excluded from participation.

Arm/Group Title	Varenicline
Arm/Group Description	Open-label; subjects will receive a behavioral intervention in addition to Varenicline. Varenicline (Chantix®, Pfizer) is an oral medication with a recommended dosage of 0.5 mg once daily for 3 days, increasing to 0.5 mg twice daily for days 4-7, and then to the maintenance dose of 1 mg twice daily for the 12 weeks of treatment.
Period Title: Overall Study
STARTED	11
COMPLETED	5
NOT COMPLETED	6

Baseline Characteristics

Arm/Group Title	Varenicline
Arm/Group Description	Open-label; subjects will receive a behavioral intervention in addition to Varenicline. Varenicline (Chantix®, Pfizer) is an oral medication with a recommended dosage of 0.5 mg once daily for 3 days, increasing to 0.5 mg twice daily for days 4-7, and then to the maintenance dose of 1 mg twice daily for the 12 weeks of treatment.
Overall Participants	11
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	38.8 (14)
Sex: Female, Male (Count of Participants)
Female	5 45.5%
Male	6 54.5%
Region of Enrollment (participants) [Number]
United States	11 100%
Brief Questionnaire of Smoking Urges (QSU-brief) (Units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Units on a scale]	476 (89.3)
Cigarettes (per day) (Cigarettes) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Cigarettes]	15.8 (2)
Carbon Monoxide Breath Level (ppm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ppm]	20 (4.6)
Montgomery-Asberg Depression Rating Scale (MADRS) (Units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Units on a scale]	9.9 (1.5)
Young Mania Rating Scale (YMRS) (Units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Units on a scale]	1.9 (0.6)

Outcome Measures

1. Primary Outcome

Title	Carbon Monoxide Breath Level at 12 Weeks
Description	Measured by expired breath in parts per million (ppm)
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT)

Arm/Group Title	Varenicline
Arm/Group Description	Open-label; subjects will receive a behavioral intervention in addition to Varenicline. Varenicline (Chantix®, Pfizer) is an oral medication with a recommended dosage of 0.5 mg once daily for 3 days, increasing to 0.5 mg twice daily for days 4-7, and then to the maintenance dose of 1 mg twice daily for the 12 weeks of treatment.
Measure Participants	5
Mean (Standard Deviation) [ppm]	6 (2.1)

2. Secondary Outcome

Title	Montgomery-Asberg Depression Rating Scale (MADRS) at 12 Weeks
Description	MADRS is a ten-item diagnostic questionnaire which psychiatrists use to measure the severity of depressive episodes in patients with mood disorders. Each item on the MADRS is scaled 0 through 6. Lowest score = 0, would indicate no depressive symptoms. Highest score = 60, indicating extreme depression. MADRS score > 20 is syndromal depression. Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry 1979; 134:382-389.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT)

Arm/Group Title	Varenicline
Arm/Group Description	Open-label; subjects will receive a behavioral intervention in addition to Varenicline. Varenicline (Chantix®, Pfizer) is an oral medication with a recommended dosage of 0.5 mg once daily for 3 days, increasing to 0.5 mg twice daily for days 4-7, and then to the maintenance dose of 1 mg twice daily for the 12 weeks of treatment.
Measure Participants	5
Mean (Standard Deviation) [Units on a Scale]	6 (2.4)

3. Secondary Outcome

Title	Young Mania Rating Scale (YMRS) at 12 Weeks
Description	YMRS is an eleven-item, multiple choice diagnostic questionnaire which psychiatrists use to measure the severity of manic episodes in patients already diagnosed with mania. Lowest score = 0, normal subject; Highest score = 60, highly manic subject. For this scale the following scores are associated with these grades of severity: mania (YMRS = 20), hypomania (YMRS = 12), under 5 is classified as non-manic. Young RC, Biggs JT, Ziegler Ve, Meyer DA. A rating scale for mania: reliability, validity and sensitivity. BR J Psychiatry 1978; 133:429-435.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Intention to Treat (ITT)

Arm/Group Title	Varenicline
Arm/Group Description	Open-label; subjects will receive a behavioral intervention in addition to Varenicline. Varenicline (Chantix®, Pfizer) is an oral medication with a recommended dosage of 0.5 mg once daily for 3 days, increasing to 0.5 mg twice daily for days 4-7, and then to the maintenance dose of 1 mg twice daily for the 12 weeks of treatment.
Measure Participants	5
Mean (Standard Deviation) [Units on a Scale]	4 (1.5)

Adverse Events

Time Frame	12 weeks per participant
Arm/Group Title	Varenicline
Arm/Group Description	Open-label; subjects will receive a behavioral intervention in addition to Varenicline. Varenicline (Chantix®, Pfizer) is an oral medication with a recommended dosage of 0.5 mg once daily for 3 days, increasing to 0.5 mg twice daily for days 4-7, and then to the maintenance dose of 1 mg twice daily for the 12 weeks of treatment.
All Cause Mortality
	Varenicline
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Varenicline
	Affected / at Risk (%)	# Events
Total	0/9 (0%)
Other (Not Including Serious) Adverse Events
	Varenicline
	Affected / at Risk (%)	# Events
Total	5/9 (55.6%)
Cardiac disorders
Elevated blood pressure	1/9 (11.1%)	1
General disorders
Lack of concentration	1/9 (11.1%)	1
Musculoskeletal and connective tissue disorders
Compartmental Syndrome	1/9 (11.1%)	1
Psychiatric disorders
Worsening Depression	2/9 (22.2%)	2

Limitations/Caveats

Small sample size; limitations finding participants with stable state within their bipolar disorder.

More Information

Certain Agreements

All Principal Investigators ARE 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.