Genetic markers associated with abstinence length in alcoholics treated with acamprosate.
Karpyak et al 2013
SUPPLEMENTAL MATERIALS
Description of the Study Sites
The Department of Psychiatry and Psychology at the Mayo Clinic in Rochester, MN has
outpatient treatment programs with and without residing beds directed by Board Certified
addiction psychiatrists. The Intensive Addiction Program (IAP) is a 30-day long intensive
outpatient treatment program, with residing beds. It serves individuals 18 years and older with
chemical dependence and dual-disorders. It includes day time (8:15 a.m.-4:30 p.m.) and
evening programming 7 days per week. Program components include Focus Groups, Process
Groups, Structured Groups, Experiential Groups, and an Intensive Family Program every other
Monday. Sobriety monitoring includes daily breathalyzer and random Drug Abuse Surveys. The
Outpatient Addiction Program (OAP) is an intensive outpatient treatment program without
residing beds. It also serves individuals 18 years and older with chemical dependence and dualdisorders. It includes daily Monday through Friday meetings from 8:30-11:30 a.m. for a total of
20 days. Components include Structured Groups, Process Groups, every other Friday Family
Day and individual counseling. Sobriety monitoring includes daily breathalyzer and random Drug
Abuse Surveys. Step-down programs for those who have completed a one-month primary
treatment program are available on site.
Addiction Recovery and Fountain Centers are free standing addiction programs for the
Mayo Clinic Austin and Albert Lea practices, respectively. The Fountain Centers Residential
Treatment Program in Albert Lea, MN has counselor-led residential and outpatient treatment
services for persons 17 and older which are directed by a licensed psychologist/clinical director.
Patients come from a variety of referral sources regionally and are followed by a medical doctor
in a local Medical Center for medication management and medical issues. The Addiction
Recovery Services Program in Austin, MN has a counselor-led outpatient program for persons
13 and older. Most of the patients are referred to this program and followed by psychiatrists on
staff in the Department of Psychiatry and Psychology Mayo Clinic Austin & Albert Lea. Stepdown programs for those who have completed a one-month primary treatment program are
available on site in Albert Lea but not in Austin.
The Mayo Clinic Health System Franciscan Healthcare Residential Services in La
Crosse, WI has a counselor-lead residential program and outpatient treatment programs which
serve persons 18 and older and has an inpatient unit for subjects with dual diagnosis. Most of
the patients are referred to this program and followed by local psychiatrists. Step-down
programs are not available on site.
All programs integrate 12 Steps of Alcoholics Anonymous facilitation with other
treatment modalities such as group and individual therapy, family therapy and continuing care
planning with an emphasis on relapse prevention skills.
Genetic markers associated with abstinence length in alcoholics treated with acamprosate.
Karpyak et al 2013
Supplemental Table S1: Subject recruitment per study site
Recruitment Site
Number recruited
Mayo Clinic Rochester
148
Albert Lea, MN
140
Austin, MN
47
La Crosse, WI
43
Self-Referral
63
Total
443
Percent
33
32
11
10
14
100%
Assessment of study participant in the discovery sample:
Study assessments were concluded by trained Clinical Research Coordinators during
the baseline and follow up visits. Detailed description of assessments is presented in the
Supplemental Table S2. The semi-structured interview (PRISM) 1 was conducted by trained
clinical research coordinators and reviewed by study clinicians to systematically assess for
lifetime presence of alcohol dependence and comorbid psychiatric disorders. Alcohol
consumption was assessed using Time Line Follow Back (TLFB, 2). Gamma-glutamyl
transpeptidase (GGT) measurements were used to assess the accuracy of self-reported
sobriety. Frequency, intensity, and duration of craving were assessed with the Penn Alcohol
Craving Scale (PACS) 3, 4. The Inventory of Drug Taking Situations (IDTS) 5, 6 was used to
assess the association of alcohol use with positive or negative emotional states. The 9 item
depression scale from the patient health questionnaire (PHQ-9) 7, and the Generalized Anxiety
Disorder Assessment (GAD-7) 8 were used to assess for the presence and intensity of
symptoms of depression and anxiety. Alcoholic Anonymous attendance monitoring (AAM)9 was
used to estimate utilization of support networks.
Face to face follow up visits were conducted at 1 month of acamprosate treatment to
assess compliance and answer questions and at 3 months to assess treatment outcomes. In
addition, subjects were contacted by phone after 2 months of treatment to assess alcohol use
(TLFB reflecting previous 30 days) and compliance with medication use (per pill count). Follow
up visits occurred within a window of 30+/- 7 days, 90+/-14 days and 180+/-14 days. The use of
other medications including anti-depressants, benzodiazepines and mood stabilizers was also
monitored at baseline and follow up visits, and baseline medication data was considered as
potential covariates in the analyses.
Genetic markers associated with abstinence length in alcoholics treated with acamprosate.
Karpyak et al 2013
Supplemental Table S2: Study procedures and assessments
Study
Baseline
Assessments
Blood
X
Collection
Medication
X
start
X
PRISM
X
CIWA-R
X
TLFB
X
PHQ-9
X
GAD-7
AAM
X
PACS
X
IDTS
Compliance
X
CTA
X
GGT
1 month
2 month
X
3 month
4 month
5 month
X
6 month
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Definitions: PRISM: Psychiatric Research Interview for Substance and Mental Disorders.
CIWA-R: Clinical Institute Withdrawal Assessment-Research. TLFB: The Alcohol Timeline
Follow Back. PHQ-9: 9 item depression scale from the patient health questionnaire; GAD-7:
Generalized Anxiety Disorder Assessment. AAM: AA attendance monitoring. PACS: Penn
Alcohol Craving Scale. IDTS: Inventory of Drug Taking Situations. CTA: Commitment to
Abstinence. GGT: gamma-glutamyl transpeptidase.
Medical and psychiatric reasons for exclusion from the discovery study:
Unstable psychiatric conditions: active suicidal ideation or psychotic disorder.
Unstable medical conditions: renal impairment with creatinine level > 1.5 mg/dL, elevated liver
function tests, active hepatitis, cirrhosis or hepatic insufficiency.
Genetic markers associated with abstinence length in alcoholics treated with acamprosate.
Karpyak et al 2013
Supplemental Table S3: Candidate genes selected for analyses of association with
treatment outcome in the discovery sample.
Gene set
Gene symbol
Glycine and GRIN1, GRIN2A, GRIN2B, GRIN2C, GRIN2D,
Glutamate
GRIN3A, GRIN3B
signaling
GLRA1, GLRA2, GLRA3, GLRB
Protein function
NMDA receptor
subunits
Glycine receptor
subunits
Glycine and
Glutamate
transporters
Glycine
metabolism
Glutamate
metabolism
Acamprosate
response
Alcoholism
and
treatment
response
SLC6A5, SLC6A9
Glycine reuptake
SLC1A2
SHMT1, SHMT2
AMT, DLD, GCSH, GLDC
GOT1
GLUL, GLUD1
Glutamate reuptake
Glycine synthesis
Glycine metabolism
Glutamate synthesis
Glutamate metabolism
10-12
GATA4, PER2, SLC29A1, ADORA1, ADORA2
13-15
MTHFR, ARNTL, ARNTL2, ADCYAP1, VIP, NPY
Supplemental Table S4: Candidate SNPs selected for analyses in discovery sample and
their association with the length of sobriety during first 90 days of acamprosate
treatment in the discovery sample.
Legend: NA, not applicable. Table S4 provided in a separate file.
Genetic markers associated with abstinence length in alcoholics treated with acamprosate.
Karpyak et al 2013
Supplemental Figure S1: GGT plasma levels in the discovery sample collected at baseline and
at 90 day follow up.
Legend: Subjects who reported no alcohol use during 3-month since beginning acamprosate
were considered abstainers, while those reporting any alcohol use were considered nonabstainers.
Genetic markers associated with abstinence length in alcoholics treated with acamprosate.
Karpyak et al 2013
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