In 2004, acamprosate was approved in the U.S. for abstinence maintenance, by decreasing
craving, in alcoholic patients who have undergone detoxification. while a new anti-craving
drug was encouraging, only 36.1% of the subjects treated with acamprosate remained abstinent
for 6 months. Having the ability to identify treatment responsive individuals would have a
major impact on the use of acamprosate.
The primary objective of this pharmacogenomic probe study of acamprosate is to identify
genetic variations that predict response. Our hypothesis is that effective acamprosate
response in alcohol dependent subjects may be influenced by genetically controlled variation
in the functionality of the N-methyl-D-aspartate receptor (NMDA) and/or the type 5
metabotropic glutamate receptor (mGluR5). Hypothesis confirmation could lead to development
of effective individualized treatment recommendations for alcohol dependent patients based
on pharmacogenomically relevant genetic variations.
The general goal is to identify genetic polymorphic variants that differentiate subjects
continuously abstinent for six months while taking acamprosate from relapsed subjects. The
initial analysis will determine whether any of ten polymorphisms in four target genes
(GRIN1, GRIN2A and GRIN2B that code for the NMDA receptor and GRM5 that codes for the type
mGluR5 receptor) are associated with successful abstinence. Subsequent analyses will examine
whether variation in a comprehensive set of 383 linkage disequilibrium haplotype tagged
single nucleotide polymorphisms of these four genes predicts successfully abstinent
1. Male or females, Age 18-80.
2. 2. Primary diagnosis of alcohol dependence based on DSM-IV-TR criteria and determined
by the Psychiatric Research Interview for Substance and Mental Disorders (PRISM)
(stable mood and anxiety disorders will not be exclusionary).
3. Prior enrollment in the IRB approved protocol "Developing a DNA Repository for
Genomic Studies of Addiction: A Pilot Study".
1. Inability to provide informed consent.
2. Inability to speak English.
3. History of hypersensitivity or allergic reaction to acamprosate.
4. Moderate to severe renal impairment, as determined by a creatinine level > 1.5 mg/dL.
5. Diagnosis of primary biliary cirrhosis, chronic active hepatitis, and drug-induced
hepatic insufficiency, as noted in the medical record.
6. Women who are pregnant, lactating, or are planning to become pregnant during the next
7. Any unstable active medical or additional psychiatric condition as determined by the
9. Active suicidal ideation as determined by responses provided during PRISM or as
determined by the investigator.