The aim of the proposed pilot study is to find out whether varenicline (ChantixTM) treatment
decreases alcohol use and smoking in patients with schizophrenia or schizoaffective
disorder. Varenicline may also improve cognition (memory and concentration) and negative
symptoms (e.g. poor attention, poverty of speech, apathy, affective flattening, anhedonia)
in patients with schizophrenia and comorbid nicotine and alcohol dependence.
Alcohol use (more than 33%) and smoking (80-90%) commonly occur together in patients with
schizophrenia. Varenicline (ChantixTM) has been approved by the FDA as a medication for
smoking cessation. Recent animal studies have shown that chronic varenicline administration
decreased alcohol consumption. There are no human data available on the effectiveness of
varenicline in alcohol-use disorders.
The aim of the proposed pilot study is to find out whether varenicline treatment decreases
alcohol use and smoking in patients with schizophrenia or schizoaffective disorder.
Varenicline may also improve cognition (memory and concentration) and negative symptoms
(e.g. poor attention, poverty of speech, apathy, affective flattening, anhedonia) in
patients with schizophrenia and comorbid nicotine and alcohol dependence.
The proposed pilot study will enroll a cohort of up to 30 subjects with schizophrenia or
schizoaffective disorder and nicotine and alcohol dependence, who are receiving ongoing
outpatient mental health treatment from community providers. Subjects will be randomly
assigned to one of the two treatment groups (varenicline vs. placebo). Following a one week
screening phase, participants will be seen on day 4, day 8, then weekly over an 8-week
treatment period. One week supply of medication will be dispensed at each study visit, with
the exception of the first week, when only 4 days supply will be given on 2 days (visit 1
and 2). One month after discontinuation of medication, a follow-up interview will be
Varenicline and placebo will be dispensed in 0.5 mg and 1 mg color coded capsules. During
the first 3 days of treatment, participants will take one 0.5 mg tablet of varenicline (or
placebo) by mouth daily. If the medication is well-tolerated, the dose will be increased to
0.5 mg by mouth twice daily for 4 days. From day 8, the dose will be increased to the
standard dosing schedule of 1 mg (1 tablet) by mouth twice daily. At the end of the 8th
week, varenicline will be discontinued.
A structured clinical psychiatric interview and physical exam will be performed at baseline,
along with a urine drug screen, which will be repeated on week 8, and at 1 month follow-up.
Blood tests (complete blood count, basic metabolic panel, liver function tests) will be
performed at baseline, then monthly.
During weekly study visits patients will undergo breath carbon-monoxide and breath alcohol
testing, and they will answer questions about depression, smoking and alcohol use. Detailed
assessment of psychiatric symptom severity (including neuropsychological testing) will be
performed at baseline, at the end of the treatment phase (week 8). A functional MRI study
will be performed at baseline and at the end of study to assess changes in blood flow,
emotional processing and working memory related to varenicline treatment. In addition,
genetic polymorphism of the α4β2 nicotinic acetylcholine receptor and gene expression
changes related to drinking/smoking/psychosis and varenicline treatment will also be
The primary objectives of the proposed study are two fold: first to determine the
feasibility of conducting a similar study on a larger scale, and second to establish pilot
data for determining the effect size for hypothesized treatment effects on alcohol and
nicotine use based on objective tests and self report. These estimates will help inform the
minimum sample size needed for a larger future trial.
- Males or females, ages 18 to 69, with a DSM-IV diagnosis of Schizophrenia or
Schizoaffective Disorder, receiving outpatient psychiatric treatment
- Currently taking antipsychotic medication for at least 4 weeks (medication is
prescribed, compliance assessed based on self-report and collateral information)
- Current DSM-IV diagnosis of Nicotine Dependence
- Current DSM-IV diagnosis of Alcohol Dependence
- Subject expresses a desire to cut down or quit smoking and drinking (based on
assessment with contemplation ladder)
- An average of at least one pack of cigarettes per day (>=20 cigarettes/day) over the
7 days prior to intake
- An average of at least 7 drinks over the 7 days prior to intake
- Inability to give adequate informed consent
- Currently taking sustained - release bupropion (Zyban) or receiving any other form of
bupropion, such as Wellbutrin or Wellbutrin SR; receiving another form of
pharmacological smoking cessation treatment (e.g., nicotine gum or patch); or
participating in another structured, formal smoking cessation program.
- Currently taking naltrexone (ReVia), Campral or Antabuse
- Participation in a clinical trial less than 3 months prior to intake
- History of suicide attempt in the past year
- History of hospitalization due to suicidal ideation in the past year
- Suicidal ideation at baseline
- Known allergic reaction to varenicline
- Female patients of childbearing potential who are sexually active, not sterile, and
who deny using a form of birth control.
- Female patients who are pregnant or nursing.
- Significant unstable medical problems (e.g. impaired renal function).
- Significant unstable psychiatric disorders.
- Subjects who do not attend all required screening appointments.
- Subjects who have pending legal proceedings whose outcome may lead to incarceration
within 3 months of intake.
- Positive urine drug screen for cocaine, opioids or amphetamine at baseline
- Current DSM-IV diagnosis of Cocaine, Opioid or Cannabis Dependence (1 month prior to
- Metal implants or devices (e.g. aneurysm clips, cochlear implants, neural
stimulators, cardiac pacemakers)
- Weight over 250 lbs