Pharmacological and Nonpharmacological Treatment of Alcohol Dependence

1
Pharmacological and Nonpharmacological Treatment
of Alcohol Dependence

• Sponsored by
• American Society of Addiction Medicine (ASAM)
• Supported by
• Florida Society of Addiction Medicine (FSAM)
• Southern Coast Addiction Technology Transfer
  Center (SCATTC)

2
Faculty
Jeffrey D. Kamlet, MD Private Practice, Internal
Medicine Forensic, Addiction, and Bariatric
Medicine Adjunct Professor of Medicine School of
Graduate Health Sciences Barry University Miami,
Florida Vineet Mehta, MD President Center for
Non-Addictive Living Attending Physician Circles
of Care Private Practice, Psychiatry and
Addiction Psychiatry Melbourne, Florida
3
ASAM Disclosure of Relevant Financial
Relationships Content of Activity
Pharmacological and Nonpharmacological Treatment
of Alcohol Dependence 2006 Courses
4
Glossary of Terms

• Commercial Interest - ACCME defines a commercial
  interest as any proprietary entity producing
  healthcare goods or services, with the exemption
  of nonprofit or government organizations and
  non-healthcarerelated companies.
• Financial relationships - Financial relationships
  are those relationships in which the individual
  benefits by receiving a salary, royalty,
  intellectual property rights, consulting fee,
  honoraria, ownership interest (eg, stocks, stock
  options or other ownership interest, excluding
  diversified mutual funds), or other financial
  benefit. Financial benefits are usually
  associated with roles such as employment,
  management position, independent contractor
  (including contracted research), consulting,
  speaking and teaching, membership on advisory
  committees or review panels, board membership,
  and other activities from which remuneration is
  received, or expected. ACCME considers
  relationships of the person involved in the CME
  activity to include financial relationships of a
  spouse or partner.
• Relevant financial relationships - ACCME focuses
  on financial relationships with commercial
  interests in the 12-month period preceding the
  time that the individual is being asked to assume
  a role controlling content of the CME activity.
  ACCME has not set a minimal dollar amount for
  relationships to be significant. Inherent in any
  amount is the incentive to maintain or increase
  the value of the relationship. ACCME defines
  relevant financial relationships as financial
  relationships in any amount occurring within the
  past 12 months that create a conflict of
  interest.
• Conflict of Interest - Circumstances create a
  conflict of interest when an individual has an
  opportunity to affect CME content about products
  or services of a commercial interest with which
  he/she has a financial relationship.

5
Supported by

• Supported by an unrestricted educational grant
  from Forest Pharmaceuticals, Inc.

6
Meeting Agenda

• 100 PM 110 PM Introductions/Welcome
• FSAM State Chapter President and Faculty
• 110 PM 315 PM Presentations
• (Each presentation consists of a lecture and Q
  A session)
• Module 1 Effective Treatment for Alcohol
• Dependence Pharmacotherapy Options
• Module 2 Effective Treatment for Alcohol
• Dependence Integrating Evidence-Based Behavioral
  Interventions and Treatments and Psychosocial
  Support Services With Pharmacotherapy
• Module 3 Concomitant Conditions Psychiatric,
  Medical, and Other Substance Use
• 315 PM 330 PM BREAK
• 330 PM 500 PM ASAM/NAADAC Panel Discussion
  Strengthening Physician/Counselor Relationships
  for Improved Patient Outcomes in the Treatment of
  Alcohol Dependence
• 500 PM 515 PM Evaluation and Adjournment

7
To Receive Credit

• Complete and return the survey and program
  evaluation form to Denise Petrone
• Before leaving, please sign the registration card
• ASAM will mail you your certificate

8
Effective Treatment for Alcohol Dependence
Pharmacotherapy Options Module 1
9
Program Objectives

• At the conclusion of this activity, participants
  should be able to
• Review clinically relevant developments and
  research in the use of disulfiram, naltrexone,
  and acamprosate for alcohol dependence disorder
• Identify and discuss clinical issues relative to
  the use of pharmacotherapy
• Review and discuss existing and promising
  treatment and management options for alcohol
  dependence
• Discuss evidence-based behavioral intervention
  and treatment, which includes integration of
  psychosocial support services with
  pharmacotherapy
• Review relevant clinical information on
  concomitant conditions

10
Module 1 Overview

• The scope of the problem
• Alcoholism is a brain disease
• Pharmacotherapy for alcohol dependence
• Pharmacotherapy in practice

11
Prevalence of Alcohol Use
NIAAA National Epidemiologic Survey onAlcohol
and Related Conditions (NESARC)
Any Alcohol Disorder 17.6 million (8.5)
Alcohol Dependence 7.9 million (3.8)
Alcohol Abuse 9.7 million (4.7)
NIAAANational Institute on Alcohol Abuse and
Alcoholism. Grant BF et al (2004).
12
Epidemiology

• Eight million adult United States citizens are
  dependent on alcohol
• Alcoholism tends to run in families and affects
  minors
• More than 50 of American adults have a past
  history or close relationship with alcoholism
• 25 of minors have been exposed to familial
  alcoholism or alcohol abuse
• Alcohol use is implicated in approximately 25
  of violent crimes and more than 16,000 fatal car
  accidents each year
• National alcoholism costs are approximately 185
  billion each year

Individuals younger than 18 years of age.
13
Societal Costs of Alcohol Dependence
Total Cost 184.6 Billion
7,466 (4)
24,093 (13)
15,963 (9)
10,085 (5)
2,909 (2)
1,253 (1)
36,499 (20)
86,368 (47)
Cost in millions of US dollars. FASfetal
alcohol syndrome. Key definitions correspond to
pie chart sections in clockwise order beginning
specialty alcohol services at the 12 oclock
position.
Harwood H et al. In NIH Publication No. 98-4327.
Available at http//www.niaaa.nih.gov.
14
Addiction A Brain Disease

• Neurological adaptation
• Mesolimbic DA system
• Animal studies
• Human studies

DAdopamine.
15
Brain Reward Pathways

• The VTA-nucleus accumbens pathway is
  activated by all drugs of dependence, including
  alcohol
• This pathway is important not only in drug
  dependence, but also in essential physiological
  behaviors such as eating, drinking, sleeping, and
  sex

Messing RO (2001).
16
Relapse and Conditioning

• Repeated use of alcohol has caused conditioning
  to occur in related circuits
• Now cues associated with alcohol use can
  activate the reward and withdrawal circuit
• This circuit can evoke anticipation of alcohol or
  feelings similar to withdrawal, which may
  precipitate relapse in an abstinent patient

Messing RO (2001).
17
Overview of Major Neurotransmitters Associated
With Alcohol
18
Dopamine

• General Function Regulates motivation,
  reinforcement, and fine motor control
• Specific Action by Alcohol Initiates a release
  at the NAC either directly or from projections
  via the mesolimbic system from the VTA
• Alcohol-Related Function Mediates motivation and
  reinforcement of alcohol consumption
• NACnucleus acumbens VTAventral tegmental area.

Swift RM (1999).
19
?-aminobutyric Acid (GABA)

• General Function Serves as the primary
  inhibitory neurotransmitter in the brain
• Specific Action by Alcohol Causes tonic
  inhibition of dopaminergic projections to the
  VTA and NAC. Prolonged alcohol use causes a
  down-regulation of these receptors and a
  potential for decreased inhibitory
  neurotransmission
• Alcohol-Related Function May contribute to
  intoxication and sedation inhibition of GABA
  function following drinking may contribute to
  acute withdrawal symptoms

Swift RM (1999).
20
Glutamate

• General Function Serves as the major excitatory
  neurotransmitter in the brain
• Specific Action by Alcohol Alcohol inhibits
  excitatory neurotransmission by inhibiting both
  NMDA and non-NMDA (kainite and AMPA) receptors.
  Up-regulation of these receptors to compensate
  for alcohols antagonistic effect occurs after
  prolonged exposure to alcohol, resulting in an
  increase in neuroexcitation
• Alcohol-Related Function May contribute to acute
  withdrawal symptoms inhibition of glutamate
  function following drinking cessation may
  contribute to intoxication and sedation
• NMDAN-methyl-D-aspartate AMPAa-amino-3-hydroxy-
  5-methisoxizole-4-propionic acid.

Swift RM (1999).
21
Opioid Peptides

• General Function Regulates various functions and
  produces morphine-like effects, including pain
  relief and mood elevation
• Specific Action by Alcohol Alcohol stimulates
  ß-endorphin release in both the NAC and VTA
  area. ß-endorphin pathways can lead to increased
  dopamine release in the NAC
• Alcohol-Related Function Contributes to
  reinforcement of alcohol consumption, possibly
  through interaction with dopamine

Swift RM (1999).
22
Alcohol Dependence Is A Chronic Disease
23
Similar Outcomes to OtherChronic Illnesses

• Type 1 DM 30 to 50 relapse each year
  requiring additional medical care
• HTN and asthma 50 to 70 relapse each year
  requiring additional medical care
• Addiction 40 to 60 relapse within first year

DMdiabetes mellitus HTNhypertension. McLellan
AT et al (2000).
24

• Less than 30 of patients with type 1 DM, HTN,
  and asthma adhere to prescribed diet and
  behavioral changes designed to improve function
  and reduce risk factors.

McLellan AT et al (2000).
25
Defining Alcohol Use
26
Defining the Standard Drink

• A standard drink 14 g ethanol
• 12 oz of regular beer or cooler (5 alcohol)
• 5 oz of table wine (12 alcohol)
• 1.5 oz of hard liquor (40 alcohol, 80 proof)
• The average person metabolizes about 1 standard
  drink per hour

NIAAA. Helping Patients Who Drink too Much a
Clinicians Guide NIAAA Web site.
http//pubs.niaaa.nih.gov/publications/Practition
er/CliniciansGuide2005/guide.pdf.
27
US Government Recommended Safe Levels of
Alcohol Consumption

• Men 2 drinks per day
• Women 1 drink per day

28
At-Risk Drinking

• 3 out of 10 US adults consume alcohol at levels
  that increase their risk for physical, mental
  health, and social problems
• Of those at risk, about 25 currently have
  alcohol abuse or dependence

NIAAA. Helping Patients Who Drink too Much a
Clinicians Guide NIAAA Web site.
http//pubs.niaaa.nih.gov/publications/Practition
er/CliniciansGuide2005/guide.pdf.
29
At-Risk Drinking (Contd)

• Defined as drinking at a level that causes or
  elevates the risk for alcohol-related problems
  or complicates the management of other health
  problems
• Men
• 5 or more standard drinks per day
• 15 or more standard drinks per week
• Women
• 4 or more standard drinks per day
• 8 or more standard drinks per week

Dawson DA et al (2005). NIAAA. Helping
Patients Who Drink too Much a Clinicians Guide
NIAAA Web site. http//pubs.niaaa.nih.gov/public
ations/Practitioner/CliniciansGuide2005/guide.pdf.

30
Alcohol Abuse

• DSM-IV-TR Criteria
• Maladaptive pattern of alcohol use leading to
  clinically significant impairment or distress,
  manifested within a 12-month period by at least
  1 of the following
• Failure to fulfill role obligations at work,
  school, or home
• Recurrent use in hazardous situations
• Legal problems related to alcohol
• Continued use despite alcohol-related socialor
  interpersonal problems

DSM-IV-TRDiagnostic and Statistical Manual of
Mental Disorders, 4th edition, text
revision. American Psychiatric Association. In
DSM-IV-TR. 2000.
31
Alcohol Dependence

• DSM-IV-TR Criteria
• Maladaptive pattern of alcohol use leading to
  clinicallysignificant impairment or distress,
  manifested within a12-month period by at least 3
  of the following
• Tolerance
• Withdrawal
• Loss of control over amount of alcohol consumed
• Preoccupation with controlling drinking
• Preoccupation with drinking activities
• Impairment of social, occupational, or
  recreational activities
• Use is continued despite persistent problems
  related to drinking

American Psychiatric Association. In DSM-IV-TR.
2000.
32
Pharmacologic Treatment of Alcohol Dependence
33
Treatment Overview

• Psychosocial treatments help many alcoholics
  reduce their drinking or achieve abstinence
• 40 to 70 relapse within a year
• Neuroscientific advances suggest the possibility
  of developing medications to enhance the
  effectiveness of psychosocial treatments
• These medications target neurotransmitter systems
  that mediate alcohol reward associated with its
  abuse liability and/or ameliorate neurochemical
  dysfunction in those with a biological
  predisposition to the disease

Litten RZ et al (1996). Swift RM (1999).
34
Neuropharmacological Targets for Treating Alcohol
Dependence

• Neurotransmitters and receptors
• Acetylcholine
• Adenosine (A1, A2 receptors)
• Cannabinoid receptors
• DA (D1, D2, D3, D4)
• GABAA, GABAB receptors
• Glutamate (NMDA, AMPA, kainate receptors)
• Glycine
• Norepinephrine (NE alpha a, beta ß
  receptors)
• Opioid peptides (mu µ, delta ?, kappa ?
  receptors)
• Other peptides (vasopressin, neuropeptide Y)
• Serotonin (5-HT several receptors, particularly
  5-HT3)
• Neurotransmitter transporters
• Adenosine, DA, 5-HT, NE
• Voltage-gated ion channels
• L-type, N-type calcium channels sodium channels
• Second messengers
• G-proteins, phospholipases, protein kinases,
  neurosteroids, hormones

Anton RF et al (2003). Litten RZ et al (2005).
35
Current Neuropharmacological Strategies to Reduce
Drinking Behavior

• Medications that reduce alcohol seeking or urge
  to drink (craving)
• Opioid antagonists, ondansetron, topiramate
• Medications that reduce the dysphoria and other
  symptoms of acute and protracted withdrawal
• Acamprosate, sedatives (?-hydroxybutyrate),
  baclofen, antiepileptics/mood stabilizers
  (carbamazepine, valproate, topiramate)
• Medications that reduce impulsivity/attention
  deficits
• DA agonists and antagonists, 5-HT antagonists
• Medications that reduce alcohol bioavailability
• Kudzu/bioflavonoids, a2-antagonists
• Medications that increase satiety/reduce
  appetitive drive
• Naltrexone, topiramate, cannabinoid (CB1)
  antagonists (?)
• Medications that treat comorbid psychiatric
  illnesses or reduce psychological distress
• Antidepressants (tricyclics, SSRIs),
  antipsychotics (typical and atypical),
  anxiolytics (buspirone)

SSRIsselective serotonin reuptake inhibitors.
Anton RF et al (2003).
36
Disulfiram Blocks Alcohol Metabolism

• Ethanol
• ? ? alcohol dehydrogenase
• Acetaldehyde
• ? ? aldehyde dehydrogenase
  (blocked by Antabuse)
• Acetate (Acetyle co-enzyme A)
  
• ?
• Carbon dioxide and water

37
Opioid Antagonists Basic Science

• Alcohol consumption affects the production,
  release, and activity of opioid peptides1
• Opioid peptides mediate some of alcohols
  rewarding effects by enhancing midbrain DA
  release
• Opioid antagonists suppress alcohol-induced
  reward2 and general consummatory behaviors3
• Genetic high-risk/FH individuals have an
  exaggerated alcohol-induced rise in ?-endorphin
  level, and are more responsive to naltrexone
  treatment4,5

FHpositive family history. 1. Herz A (1997).
2. Swift RM (1999). 3. Boyle AE et al (1998). 4.
Giannoulakis C (1996). 5. King AC et al (1997).
38
Opioid Antagonist Naltrexone Clinical Science

• Some studies in alcoholics have found either no
  efficacy for naltrexone1 or efficacy among only a
  subgroup with medication compliance rates of 80
  to 902,3
• Adverse events, particularly nausea, can result
  in up to 15 of withdrawals from clinical
  studies,4 and may limit acceptability in generic
  or managed care facilities
• Depot naltrexone preparations may enhance
  compliance, and one study has demonstrated
  efficacy at reducing heavy drinking in men5
• Targeted naltrexone might be another useful
  strategy to maximize compliance while diminishing
  adverse events rates6,7

1. Kranzler HR et al (2000). 2. Volpicelli JR et
al (1997). 3. Litten et al (1998). 4. Croop RS
et al (1997). 5. Garbutt JC et al (2005). 6.
Heinala P et al (2001). 7. Kranzler HR et al
(2003).
39
Opioid Antagonist Naltrexone Clinical Science
(Contd)

• Naltrexone 100 mg/day appears more efficacious
  than the usual 50 mg/day dose1,2
• Identification of the alcoholic subgroup (perhaps
  those with a biological disease predisposition)
  most responsive to naltrexone is an important
  scientific goal3
• Current evidence suggests that high craving and
  strong FH are strong predictors of a positive
  outcome4
• Preliminary evidence suggests that allelic
  variation at the mu opioid receptor gene is
  associated with differential treatment response
  to naltrexone5

1. McCaul ME et al (2000). 2. McCaul ME et al
(2000). 3. Johnson BA and Ait-Daoud (2000). 4.
Monterosso JR et al (2001). 5. Oslin DW et al
(2003).
40
Glutamate Antagonist Acamprosate Basic Science

• Excitatory neurotransmitter N-methyl-D-aspartate
  (NMDA) contributes to alcohols intoxicating,
  cognitive, and dependence-forming effects
• NMDA antagonist acamprosate reduces the intensity
  of post-cessation alcohol craving on exposure to
  high-risk drinking situations

Embellished from Spanagel and Zieglgansberger
(1997).
Spanagel and Zieglgansberger (1997).
41
Glutamate Antagonist Acamprosate Clinical
Science

• Poorly absorbed, with a bioavailability of
  approximately 10
• Excreted unmetabolized therefore, no risk of
  hepatotoxicity or interaction with alcohol
• Should be used with caution in individuals with
  renal impairment
• Relatively safe, the most common adverse event
  is diarrhea

CAMPRAL (acamprosate calcium) delayed-release
tablets prescribing information 2004.Mason et
al (2002).
42
Glutamate Antagonist Acamprosate Clinical
Science (Contd)

• Approved for the treatment of alcohol dependence
  in 29 countries and in the US in July 2004
• Methodological rigor was enhanced in later
  studies (e.g., Sass and colleagues1 Whitworth
  and colleagues2) by standardization of diagnosing
  alcoholism, laboratory measurements, and
  psychosocial treatment regimen
• Although more than 20 clinical trials have been
  conducted, a meta-analysis of 17 positive studies
  revealed that acamprosate vs. placebo increased
  continuous abstinence rates following 3 (46 vs.
  34), 6 (36 vs. 23), and 12 (27 vs. 13)
  months of treatment3
• Acamprosate also decreases frequency of drinking
  and the intensity of a relapse if drinking is
  reinstated after abstinence4,5
• Predicators of treatment response that have been
  examined and found to have NO predictive value
  include increased levels of anxiety,
  physiological dependence, FH-, late age of onset,
  and being female6
• For a review, see Johnson and Ait-Daoud (2000)7,
  Ait-Daoud and Johnson (2003)8, and Litten et al
  (2005)9

1. Sass et al (1996). 2. Whitworth et al (1996).
3. Mann et al. (2004). 4. Chick and Lehert
(2003). 5. Tempesta et al (2000). 6. Verheul et
al (2005). 7. Johnson and Ait-Daoud (2000). 8.
Ait-Daoud and Johnson (2003). 9. Litten et al
(2005).
43
Rationale for Combining Medications

• Small to moderate effect sizes for single
  medications
• Additive or synergistic effects to interact at
  multiple neuronal systems
• Single medications might be effective at only
  particular phases of the illness
• Combinations target a wider range of alcohol
  subtypes, particularly if there is a differential
  genomic environmental response
• BUT
• Potential for increased adverse events
• Potential for lack of effect or unexpected
  antagonistic actions

44
Combined Medications for Treating Alcoholism in
the Clinic Acamprosate Plus Naltrexone

• To determine the relative efficacy of naltrexone
  (50 mg/day) and acamprosate (1998 mg/day) both
  alone and in combination
• 2 2 factorial with 40 men and women per cell
• Double-blind placebo-controlled study
• Psychotherapy weekly group coping-skills therapy
• 12-week study duration

Kiefer et al (2003).
45
Comparing and Combining Naltrexone and
Acamprosate in Relapse Prevention of Alcoholism
(N160)
Naltrexone Plus AcamprosateNaltrexoneAcamprosate
Placebo
1.0
0.9
0.8
0.7
0.6
Proportion of Survivors (Nonrelapse)
0.5
0.4
0.3
0.2
0.1
0
10
20
30
40
50
60
70
80
Time, d
Kiefer et al (2003).
46
Medications Currently Approved for Alcohol
Dependence

• Disulfiram (Antabuse)
• Naltrexone (ReVia)
• Acamprosate (Campral)

Antabuse Florham Park, NJ Odyssey
Pharmaceuticals, Inc. Campral St. Louis, Mo
Forest Pharmaceuticals, Inc. ReVia Wilmington,
De DuPont Pharmaceuticals.
47
Disulfiram (Antabuse)
Antabuse Florham Park, NJ Odyssey
Pharmaceuticals, Inc.
48
Naltrexone (ReVia)
ReVia Wilmington, De DuPont Pharmaceuticals.
49
Acamprosate (Campral)
CrClcreatinine clearance.
Campral St. Louis, Mo Forest Pharmaceuticals,
Inc.
50
Is the Primary Care Office Appropriate for
Treatment?

• Willingness and knowledge of primary care
  physician
• Stage of change (see Module 2) and willingness
  of patient
• Severity and chronicity of alcohol use disorder
  (ASAM criteria)
• Psychosocial support available within family and
  community
• Prior treatment response
• Availability of psychosocial and behavioral
  treatments
• Adherence to treatment plan

51
Monitoring Pharmacotherapy for Alcohol Dependence

• Watch for evidence of alcohol and drug use
• Ask about alcohol and drug use
• Consider blood and urine testing (alcohol and
  drug screens, biologic indicators-transaminase
  level)
• Evaluate adherence to medication and all aspects
  of treatment plan
• Monitor Alcoholics Anonymous or other group
  attendance
• Involve other care givers
• Evaluate for ongoing psychiatric illness
• Evaluate other stressors
• Monitor side effects
• Provide support

52
Patient Selection for Pharmacotherapy

• Research has yet to fully define subtypes of
  patients with alcohol dependence who respond to
  pharmacotherapy
• Naltrexone may be best for those with a FH of
  alcohol dependence and significant craving
• Medication is only useful for patients who are
  interested in treating their alcohol abuse or
  dependence
• Some physicians provide pharmacotherapy to all
  their patients with alcohol abuse and dependence,
  whereas other physicians have not yet used these
  medications
• Medication adherence is a significant problem
• Pharmacotherapy may not be effective in limiting
  other substance use

53
Summary

• Alcohol dependence is a brain disease
• Alcohol dependence is a chronic disease
• Naltrexone, acamprosate, and disulfiram are
  effective in limiting alcohol use
• Alcohol dependence can be addressed with
  pharmacotherapy in a primary care office
• When integrated with psychosocial and behavioral
  interventions

54
Effective Treatment for Alcohol Dependence
Integrating Evidence-Based Behavioral
Interventions and Treatments and Psychosocial
Support Services With Pharmacotherapy

• Module 2

55
Introduction Module 2

• Screening
• Brief interventions
• Evidence-based psychosocial and behavioral
  treatment approaches
• Project MATCH
• Alcoholics Anonymous (AA)
• Integration of pharmacotherapy and
  nonpharmacotherapy

MATCHmatching alcoholism treatments to client
heterogeneity.
56
Clinical Indications for Screening

• Key opportunities include
• As part of a routine examination
• Before prescribing a medication that interacts
  with alcohol
• In the emergency department or urgent care center
• In response to family member concerns

57
Clinical Indications for Screening (Contd)

• In patients who
• Are pregnant or trying to conceive
• Are likely to drink heavily, such as smokers,
  adolescents, and young adults
• Have health problems that might be
  alcohol-induced, such as cardiac arrhythmia,
  dyspepsia, liver disease, depression or anxiety,
  insomnia, and trauma
• Have a chronic illness not responding to
  treatment as expected, such as chronic pain,
  diabetes, gastrointestinal disorders, depression,
  heart disease, and hypertension
• A patient with signs of an emerging problem

58
Purpose of Screening

• To determine if there are indicators of an
  alcohol problem requiring further assessment and
  perhaps clinical intervention

59
Step 1 Ask About Alcohol UseHelping Patients
Who Drink Too Much NIAAA 2005
Prescreen Do you sometimes drink alcoholic
beverages?
No
Yes
Screening Complete
Ask the screening question about heavy
drinking days How many times in the past year
have you had 5 or more drinks in a day? (for
men) 4 or more drinks in a day? (for women)
60
Is screening positive? 1 or more heavy drinking
days or AUDIT score of gt5 for men or gt4 for women
No
Yes

• Your patient needs additional evaluation. For a
• more complete picture of the drinking pattern,
• determine the weekly average
• On average, how may days a week do you have an
  alcoholic drink?
• On a typical drinking day, how many drinks do you
  have?
• Record heavy drinking days in the past year and
  the
• weekly average in chart

• Advise staying within maximum drinking limits
• For healthy men up to age 65
• No more than 4 drinks in a day AND
• No more than 14 drinks in a week
• For healthy women (and healthy men over age 65)
• No more than 3 drinks in a day AND
• No more than 7 drinks in a week
• Recommend lower limits or abstinence as medically
  indicated, for example, for patients who
• Take medications that interact with alcohol
• Have a health condition exacerbated by alcohol
• Are pregnant (advise abstinence)
• Express openness to talking about alcohol use and
  any concerns it may raise
• Rescreen annually

Assess for alcohol abuse or dependence
Please refer to NIAAA Clinicians Guide for
Interview Version form.
AUDITalcohol use disorders identification test.
61
Brief Interventions

• Empirically based
• Utilized by general medical and MH practitioners
• For patients not needing, wanting, or ready to
  accept specialty care
• Brief, structured, time limited, and directed
  toward a specific goal
• Goal may be for the patient to try abstinence,
  moderation, or harm reduction
• Approach is client centered, empathetic,
  engaging, noncoercive, and flexible

62
Brief Interventions (Contd)

• Intended mainly for less severe and nondependent
  drinkers or those in early stages
• Applied in a broad array of settings outside
  traditional treatment programs such as
  office-based practices and other nonspecialized
  treatment settings
• Effective and cost effective

63
What We Know About Brief Intervention

• Decreases alcohol use in both men and women
• Decreases healthcare utilization
• Decreases costs
• 1 to 4 sessions are effective
• Physicians can be trained to conduct brief
  interventions

64
(No Transcript)
65
Goals of Brief Intervention

• Reduce risk of harm from continued substance use
• Abstinence provides the greatest degree of harm
  reduction and safety, but the specific goal for
  each individual is determined by consumption
  patterns, consequences, risks, and, above all,
  individual choice
• Only the client can choose the goal, no matter
  what you recommend and think is best!

66
Appropriate Patients for Office-Based Physician
Intervention

• Patients with low to moderately severe
  alcohol/drug problems
• Patients with more severe problems who are not
  ready to take action and/or accept referral for
  specialist consultation or treatment
• Patients determined to try to reduce/stop on
  their own with minimal guidance before
  considering other treatment options
• Intended mainly for less severe and nondependent
  drinkers or those in early stages
• Applied in a broad array of settings outside
  traditional treatment programs such as
  office-based practices and other nonspecialized
  treatment settings

67
Physicians Stance

• Be friendly and nonthreatening
• Convey an attitude of curiosity and concern
• Avoid being authoritarian or judgmental
• Reassure that all information is confidential

68
Provide Objective Feedback

• State your findings clearly, empathetically, and
  nonjudgmentally
• Stick to the facts about the nature/severity of
  problem and its consequences without drawing
  firm conclusions
• Draw connection between substance use and other
  health problems/risks, wherever possible
• State your medical concerns

69
Inform Patients About...

• Safe consumption limits for alcohol
• Definitions of substance ABUSE and DEPENDENCY
• Added risks posed by family history of alcohol or
  drug problems
• Your confidence in their ability to change
• Your willingness to help

70
Advise Patient to ABSTAIN if

• Evidence of substance abuse or dependence
• Pregnant or trying to conceive
• Contraindicated medical/psychiatric condition or
  medication
• Significant family history of alcohol/drug
  problems (at least 1 parent, grandparent, or
  sibling)

71
Advise Patient to CUT DOWN if

• Drinking above low-risk levels without current
  evidence or prior history of alcohol dependence
• Initial recommendation to abstain from
  alcohol/drugs has been rejected

72
Stages of Change

• People with alcohol/drug problems generally fall
  into 1 of 5 stages along a continuum of readiness
  to change
• This provides a useful framework for determining
  how best to approach patients in each stage of
  change and what types of interventions are most
  likely to be effective

73
Stages of Change (Contd)

• Precontemplation Patient does not see the
  behavior as a problem, no desire to change (in
  denial)
• Contemplation Patient beginning to see the
  behavior as a problem, but still wavering
  (sitting on the fence) yes, but
• Preparation Patient is considering options for
  change
• Action Patient taking specific steps to change
• Maintenance Patient preventing relapse

74
The Wheel of Change
75
Assessing Patients Readiness to Change

• Response to your feedback and advice offers
  strong clues about the patients readiness to
  change
• ASK What are your thoughts about these findings?
  
• ASK To what extent do you view your drinking as
  a problem?
• ASK Do you see a need for change?

76
Responding to Patient Resistance

• Be prepared for a range of patient reactions,
  including shame, dismay, or anger
• Avoid reacting to patient resistance as a
  challenge to your medical authority
• Avoid getting into arguments or debates about how
  much drinking is too much
• Avoid using the label addict or alcoholic
• Emphasize to the patient that only he or she can
  make the decision to change

77
Willing to Consider Changing Your Drinking?

• If NO, then
• Restate your concerns
• Encourage reflection of pros and cons of change
  versus no change
• What are the barriers to change?
• Reaffirm your willingness to help when the
  patient is ready and, at the very least, to
  reevaluate at a later time

78
If Patient Is NOT Willing to Consider Change

• Do not react to patient resistance as a challenge
  to your medical judgment or authority
• Avoid getting into arguments or debates about how
  much drinking is too much
• Avoid using the label addict or alcoholic
• Emphasize to patients that only they can make the
  decision to change you have no desire to
  pressure them to change
• Agree to disagree restate your concerns about
  need for change
• Your primary goal is to maintain an ongoing
  dialogue about their alcohol use and to continue
  to encourage change

79
Willing to Consider Changing Your Drinking?

• If YES, then
• Negotiate a Plan of Action based on
• Problem severity
• Stage of readiness to change
• Level of involvement you, as the primary care
  physician, are willing and/or able to provide
• Community resources for alcohol dependence
  treatment

80
Substance Abuse Treatment Options

• Medical detoxification
• Inpatient
• Outpatient
• Residential treatment
• Outpatient treatment
• Office-based treatment
• Addiction psychologist or psychiatrist
• Addiction medicine specialist
• AA or other self-help program

81
Scientifically Based Approaches to Addiction
Treatment

• Cognitive-behavioral therapy
• Community reinforcement
• Motivational enhancement therapy
• 12-step facilitation
• Contingency management
• Pharmacologic therapies
• Systems treatment
• Behavioral couples therapy
• Multidimensional family therapy

National Institute on Drug Abuse (1999). Onken
L (2002).
82
Alcoholics Anonymous

• More people use AA than any other resource to
  address problems with alcohol.
• McCrady Miller (1993)
• Weisner, Greenfield, Room (1995)

McCrady Miller (1993). Weisner C et al (1995).
83
12-Step Programs

• Accessible
• Inclusive
• Adaptable/diverse
• Growing
• Inexpensive
• Successful

84
Estimated AA Membership (January 2004)

• Members in United States 1,187,168
• Groups in United States 52,735
• Members Worldwide 2,066,851
• Groups Worldwide 104,589
• (AA is found in over 150 countries)

AA. Available at http//alcoholics-anonymous.org.
2005.
85
Efficacy of AA
Timko C et al (2000).
86
AA Activities That Positively Correlated to
Drinking Outcomes

• Having a sponsor
• Engaging in 12-step work
• Leading a meeting
• Increasing ones degree of participation in the
  organization compared to a previous time
• Sponsoring other AA members
• Working the last 7 of 12 steps

87
Integration Is Necessary

• Pharmacotherapy for alcohol dependence should
  always be accompanied by psychosocial and/or
  behavioral treatments

88
Integration

• Monitor abstinence and adherence to treatment
• Support abstinence, pharmacotherapy, and
  psychosocial/behavioral treatment
• Discuss medication as it fits with recovery,
  psychotherapy, and AA
• Involve other caregivers
• Ongoing evaluation of appropriate level of care
• Evaluate for ongoing psychiatric illness
• Evaluate other stressors
• Provide support

89
Summary

• Screening should be done in all primary care
  offices
• Brief interventions are effective
• Many psychosocial and behavioral treatmentsare
  effective
• Integration of pharmacotherapy and
  nonpharmacotherapy is necessary

90
Concomitant Conditions Psychiatric, Medical,
and Other Substance Use

• Module 3

91
Medical Comorbidities
92
Some Early Clues to Problem Drinking

• Injuries
• Infections
• Gastritis and duodenitis
• Hematologic effects
• Early hepatic markers

93
As Alcoholism Progresses, the Clinician Will Also
Observe

• Hepatic effects
• Cardiac effects
• Pancreatic effects
• Nervous system effects
• Mental health effects
• Cancer

94
Psychiatric Comorbidities
95
Initial Evaluation and Treatment of Psychiatric
Disorders

• In those with active substance use, the following
  must be taken into account
• Psychiatric symptoms associated with substance
  use and withdrawal
• Consequences of substance use
• Substance induced psychiatric disorders
• Withdrawal syndromes
• Overlapping symptoms, enmeshed course

96
High Rates of Psychiatric Comorbidity in Alcohol
Dependence

• 78 of male alcoholics have a coexisting lifetime
  history of a psychiatric disorder
• 86 of female alcoholics have a coexisting
  lifetime history of a psychiatric disorder

Kessler RC et al (1997).
97
ECA Data
Lifetime Prevalence ()
ECAepidemiologic catchment area.
98
ECA Data (Contd)

• Patients with a psychiatric disorder
• 22 also had an alcohol disorder
• 15 also has a drug disorder
• Patients with an alcohol disorder
• 37 had a psychiatric disorder
• Patients with a drug disorder
• 53 had a psychiatric disorder

99
Lifetime Prevalence ofAlcohol Use
Abuse/dependence. BDIbipolar disorder type I
BDIIbipolar disorder type II DYSdysthymia
GPgeneral population MDmajor depression
OCDobsessive compulsive disorder PDpanic
disorder SZschizophrenia. Regler DA et al
(1990).
100
Evaluation

• Diagnosis difficult due to symptom overlap and
  enmeshed course
• Account for substance-induced psychiatric
  disorder and withdrawal associated symptoms
• History of psychiatric illness
• Onset
• Periods of abstinence
• Family history
• Prior treatment
• Denial, inadequate history
• Relapse
• May require multiple visits

101
Treatment Guidelines

• Nonaddicting medications, if possible
• Educate about addiction and psychiatric illness
• Account for complex feelings, attitudes, and bias
  toward comorbidity and treatment
• Chronic illness model

102
Psychotherapy

• Essential to treatment of psychiatric illness
• Combine with knowledge of 12 steps
• Cognitive behavioral or interpersonal therapy

103
Other Substance Use Is the Norm
104
Lifetime Prevalence of Alcohol Dependence in Drug
Dependence
Alcohol Abuse/Dependence Lifetime Prevalence ()
THCtetrahydrocannabinol.
105
Estimated Prevalence of Dependence Among 15- to
54-Year-Olds, 1990-1992 (NCS)
NCSNational Comorbidity Survey. Adapted from
Anthony JC et al. Exp Clin Psychopharmacol.
19942244-268.
106
Other Substance Use

• Use of other drugs complicates treatment of
  alcohol dependence
• Pharmacotherapies are only available for alcohol
  and opioids (maintenance treatment)
• Other substance use responds to psychosocial and
  behavioral interventions and treatments
• Other substance use will be addressed in
  addiction treatment programs

107
Summary

• Medical and psychiatric comorbidities as well as
  use of other substances complicate the treatment
  of alcohol dependence

108
Course Summary

• Pharmacotherapy for alcohol dependence has the
  potential to improve outcomes when integrated
  with the psychosocial and behavioral therapies
  during the first 12 to 18 months of recovery
  the highest risk period for relapse

109
Case Vignettes
110
Case 1

• Susan is a 40-year-old executive who has come in
  for evaluation of a sleep disturbance. Her
  alcohol screen was negative, but she admits that
  she drinks 1 to 2 glasses of wine about 2 times
  per week. She denies any work-related stress,
  legal issues, and drug use. Her family history is
  negative for alcohol dependence, but she does
  state that her marriage is a bit troubled.
• 1. Is her alcohol use a concern? Why or why not?

111

• Case 1 (Contd)
• Due to the reference made to marital
  difficulties, you obtain a release of information
  and contact her husband. He describes a
  remarkably different situation, stating that he
  is considering a divorce due to Susans drinking.
  He says that she drinks daily, often at least a
  bottle of wine, but she is adept at hiding it so
  he is not sure how much she actually drinks. She
  is performing poorly at her new job in fact she
  is on probation. This is her third job in the
  past 2 years. He has noticed morning sweats and a
  tremor. Her father died a very heavy drinker.

1. What treatment recommendations would you
consider at this time?
112

• Case 1 (Contd)
• Susan returns for a follow up appointment aware
  of your discussion with her husband. She admits
  to drinking one to two bottles of wine per night,
  a marked increase in tolerance, regular
  withdrawal symptoms and dysfunction in multiple
  areas of her life. She is now seeking your help.

1. What is her differential diagnosis? 2. Would
you prescribe a pharmacological treatment? If
so, discuss why and which one.
113

• Case 2
• John is a 24-year-old construction worker who has
  been sent in for evaluation by his employer after
  a urine drug screen revealed cannabis. He admits
  to occasional use, and says it was bad luck
  that resulted in the positive urinalysis. He
  wants to return to work and says he will quit
  using cannabis immediately. He describes regular
  alcohol use, primarily beer, about 4 cans a day
  on weekends. The physical exam is normal,
  laboratory tests are normal, and he does not have
  a family history of alcohol or drug-related
  problems.

1. What are your concerns about his
presentation? 2. What is your treatment
plan? 3. How would you advise his supervisor?
114

• Case 2 (Contd)
• Six months later you see John in the emergency
  room after he cut off three fingertips at work.
  His drug screen is positive for methamphetamine,
  cannabis, and alcohol. He has been threatened
  with job loss. He lives alone and does not have
  any close friends or family. John admits to daily
  use of a combination of alcohol and other drugs
  his tolerance for alcohol has dramatically
  increased. He states that he is happy with his
  lifestyle, making good money and partying. He
  does want to keep his job.

1. What is your differential diagnosis
now? 2. How would you go about discussing this
situation with John?
115

• Case 2 (Contd)
• John agrees to quit methamphetamine and cannabis,
  but does not want to stop drinking. His
  supervisor wants him clean and sober, or he
  cannot keep his job.

1. How would you advise John? 2. How would you
advise his supervisor? 3. What treatment
recommendations would you make? 4. Would you
prescribe a pharmacological treatment? If so,
discuss why and which one.
116
Acknowledgments

• Slides have been provided by
• Addiction Technology Transfer Center (ATTC)
• National Institute on Alcohol Abuse and
  Alcoholism (NIAAA)
• Bankole Johnson, MD
• Norman S. Miller, MD
• John Patz, DO
• Edwin A. Salsitz, MD, FASAM
• Marvin D. Seppala, MD
• Valerie Slaymaker, PhD
• J. Scott Tonigan, PhD
• Arnold M. Washton, PhD
• Clinical Practice Guidelines for Substance Use
  Disorders- Veterans Administration Office of
  Quality and Performance

117
Acknowledgments (Contd)

• The faculty would like to acknowledge the ASAM
  staff who made this project come to life
• Angela Warner
• Tracy Gartenmann
• Gionne Graetz

118
To Receive Credit

• Complete and return the survey and program
  evaluation form to Denise Petrone
• Before leaving, please sign the registration card
• ASAM will mail you your certificate
• Thank you for your participation.