Extended-Release vs. Oral Naltrexone Alcohol Treatment in Primary Care

Rationale: Though integration of alcohol pharmacotherapy into primary care settings is
receiving increasing emphasis and support, rigorous data to inform clinicians' treatment
choice is lacking. The most recently FDA-approved alcohol treatment medication, an
extended-release depot form of naltrexone (XR-NTX, Vivitrol®), could greatly simplify the
medical home-centered alcohol treatment emphasized in the National Institute on Alcohol Abuse
and Alcoholism (NIAAA) Clinician's Guide. Injected once a month, XR-NTX offers a long-acting
and thus potentially more effective form of pharmacotherapy than oral naltrexone (O-NTX),
which, despite the Combined Pharmacotherapies and Behavioral Interventions for Alcohol
Dependence (COMBINE) trial and systematic reviews supporting some efficacy, has been
characterized by low rates of overall prescribing, poor adherence, suboptimal monthly refill
and inadequate treatment retention. Yet while promising as an alternative to O-NTX, XR-NTX is
substantially more expensive (~$1100 vs. ~$100 per month), and no head-to-head trials have
compared the two forms of naltrexone. A comparative effectiveness approach is required to
systematically evaluate the following key questions: In primary care settings, what is the
relative clinical effectiveness of XR-NTX vs. O-NTX? What are the benefits and costs of
XR-NTX relative to O-NTX? And can patient and system characteristics be identified to inform
treatment choice to maximize the probability of successful outcome?

Implications: Despite several years of experience, the comparative effectiveness of XR-NTX
compared to older alcohol medications remains uncertain, particularly in a mainstream,
primary care treatment model that is generalizable and broadly accessible. Newer, novel,
expensive medications for addiction disorders are historically greatly underutilized by
primary care physicians. This study is innovative both as a 'head-to-head' evaluation of
XR-NTX vs. O-NTX in primary care, and because expected participants will be primarily
Medicaid-covered or uninsured persons who will not be excluded based on medical and
psychiatric co-morbidities that often preclude participation in efficacy studies. If health
insurance expansion, parity reforms, medical homes and accountable care organizations are to
define primary care as a core alcohol treatment setting in the coming decade, exactly this
type of study is required to guide treatment protocols and resource allocation. Ultimately,
more widespread adoption of cost-effective alcohol pharmacotherapies will result in
longer,healthier lives and lower costs.

Inclusion Criteria:

- Adults, age >18 y.o.

- English- or Spanish- speaking and able to understand study procedures and provide full
consent.

- DSM IV diagnosis of alcohol dependence as determined by study physician and DSM IV
checklist.

- Endorses goal of abstinence, and is able to achieve alcohol abstinence without
inpatient detoxification, per study physician.

Exclusion Criteria:

- Current opioid dependence and/or positive urine toxicology for extended opioids.

- Pregnancy or female planning conception.

- Allergy to naltrexone or the PGL XR-NTX formulation or diluent.

- Severe liver disease, liver failure, or liver function test levels greater than three
times normal.

- Other severe, untreated or uncontrolled medical illness (e.g., severe heart failure or
dementia).