Clinical trial NCT00813800: Varenicline in Bipolar Depressed Patients
Official title: Varenicline for Smoking Cessation in Bipolar Depressed Patients: An Open-Label 12-week Feasibility Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Smoking
Bipolar Disorder
Depression
Keywords: Smoking
Bipolar Disorder
Depression
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2008-12-23
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Carbon Monoxide Breath Level at 12 Weeks
timeFrame: 12 weeks
Secondary outcomes:
measure: Montgomery-Asberg Depression Rating Scale (MADRS) at 12 Weeks
timeFrame: 12 weeks
measure: Young Mania Rating Scale (YMRS) at 12 Weeks
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Mark A. Frye, M.D.
role: PRINCIPAL_INVESTIGATOR
References: