Bipolar Disorder, Depression, Smoking
Conditions
Keywords
Smoking, Bipolar Disorder, Depression
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%.
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).
Interventions
DRUGVarenicline
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.
Sponsors
Pfizer
Mark Frye
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Carbon Monoxide Breath Level at 12 Weeks | 12 weeks | Measured by expired breath in parts per million (ppm) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Countries
United States
Participant flow
Recruitment details
11 patients were enrolled from the community all with bipolar depression and the desire to stop smoking.
Pre-assignment details
36 patients who were screened did not meet inclusion/exclusion criteria and excluded from participation.
Participants by arm
| Arm | Count |
|---|---|
| Varenicline 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. | 11 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Screen Failure after Consent | 2 |
| Overall Study | Worsening of depression | 2 |
Baseline characteristics
| Characteristic | Varenicline |
|---|---|
| Age Continuous | 38.8 years STANDARD_DEVIATION 14 |
| Brief Questionnaire of Smoking Urges (QSU-brief) | 476 Units on a scale STANDARD_DEVIATION 89.3 |
| Carbon Monoxide Breath Level | 20 ppm STANDARD_DEVIATION 4.6 |
| Cigarettes (per day) | 15.8 Cigarettes STANDARD_DEVIATION 2 |
| Montgomery-Asberg Depression Rating Scale (MADRS) | 9.9 Units on a scale STANDARD_DEVIATION 1.5 |
| Region of Enrollment United States | 11 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 6 Participants |
| Young Mania Rating Scale (YMRS) | 1.9 Units on a scale STANDARD_DEVIATION 0.6 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 5 / 9 |
| serious Total, serious adverse events | 0 / 9 |
Outcome results
Primary
Carbon Monoxide Breath Level at 12 Weeks
Measured by expired breath in parts per million (ppm)
Time frame: 12 weeks
Population: Intention to Treat (ITT)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Varenicline | Carbon Monoxide Breath Level at 12 Weeks | 6 ppm | Standard Deviation 2.1 |
Secondary
Montgomery-Asberg Depression Rating Scale (MADRS) at 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.
Time frame: 12 weeks
Population: Intention to Treat (ITT)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Varenicline | Montgomery-Asberg Depression Rating Scale (MADRS) at 12 Weeks | 6 Units on a Scale | Standard Deviation 2.4 |
Secondary
Young Mania Rating Scale (YMRS) at 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.
Time frame: 12 weeks
Population: Intention to Treat (ITT)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Varenicline | Young Mania Rating Scale (YMRS) at 12 Weeks | 4 Units on a Scale | Standard Deviation 1.5 |