Naltrexone for At-Risk and Problem Drinking in Smoking Cessation Treatment

A substantial portion of individuals seeking behavioral and pharmacological treatment for
smoking cessation drink excessively with many reporting significant alcohol problems.
Although these at-risk and problem drinkers are unlikely to choose abstinence from alcohol
as a goal, many make substantial reductions in their drinking during and after their quit
smoking attempt. Thus, the context of smoking cessation treatment offers a unique and
valuable opportunity in which to apply brief interventions and pharmacotherapy to catalyze
change in excessive drinking in a population with markedly elevated risk for negative health
outcomes. In our recent randomized clinical trial, standard smoking cessation treatment that
incorporated a brief alcohol intervention showed promise in reducing drinking as well as in
improving smoking cessation outcomes among heavy drinkers. However, these effects were
relatively modest, especially among the heaviest drinkers, indicating that further study is
warranted of methods to address heavy drinking in smoking cessation including the use of
relevant pharmacotherapy. Naltrexone, in particular, shows promise for this purpose.

The overall aim of this project is to test the efficacy of naltrexone as a pharmacotherapy
for excessive drinking when delivered to at-risk or problem drinkers who are seeking smoking
cessation treatment. The proposed clinical trial uses a between-subjects design in which 300
at-risk or problem drinkers seeking treatment for smoking cessation will be randomly
assigned to receive either daily 50 mg naltrexone or placebo. Medication will be initiated 2
weeks prior to participants' smoking quit date and continue for 10 weeks. All participants
also will receive transdermal nicotine patch and a counseling and medication management
intervention that provides advice for smoking cessation, advice regarding the effects of
heavy drinking on both smoking cessation and health, and monitoring and encouragement of
compliance with medications. Drinking and smoking outcomes will be assessed at 2, 8, 16, and
26 weeks after participants' smoking quit date. The primary aim of the study is to test the
hypothesis that naltrexone will result in greater reductions in heavy drinking relative to
placebo. The secondary aim will test whether naltrexone results in superior smoking outcomes
relative to placebo, and tertiary aims will examine interrelationships among motivation for
changing drinking, compliance with naltrexone, and drinking and smoking outcomes.

This study represents the first of its kind to provide naltrexone in conjunction with an
opportunistic brief alcohol intervention for at-risk and problem drinkers not seeking
alcohol treatment. Testing the potential benefits of naltrexone among at-risk and problem
drinkers who smoke is of very high significance for public health efforts to reduce the
markedly elevated rates of morbidity and mortality observed in this large, yet relatively
understudied group.

Inclusion Criteria:

- 1.) be at least 18 years of age, 2.) drink heavily at least once per month on average
(≥4 drinks per occasion for women; ≥5 drinks for men), 3.) have smoked cigarettes
regularly for at least one year, 4.) currently smoke at least 5 cigarettes a day, 5.)
currently be using no other tobacco products or nicotine replacement therapy

Exclusion Criteria:

- 1.) meet criteria for current substance dependence (excluding nicotine and alcohol);
2.) report opiate use in the past month, have a drug screen positive for opiates, or
require opiate containing medications for pain management; 3.) meet criteria for a
current major depressive or manic episode; 4.) are currently psychotic or suicidal;
5.) have an unstable or serious medical condition that would preclude use of the
nicotine patch or naltrexone (e.g., unstable angina pectoris, severe arrhythmia,
recent congestive heart failure); 6.) have aspartate aminotransferase or alanine
aminotransferase levels of more than 3 times the reference range or elevated
bilirubin levels; or 7.) are currently pregnant or lactating, intend to become
pregnant, or are not using a reliable means of birth control.