Alcohol Dependence

1
Alcohol Dependence

• Ismene Petrakis, MD

2
Epidemiology

• Not Known
• ECA data 13.7 lifetime prevalence of alcohol
  abuse/dependence
• Even broader if those with alcohol-related
  problems included
• Health Care Cost
• 15 of national health care budget for secondary
  health problems
• 10 of the cost of alcoholism spent on direct
  care

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Alcoholism Definition
4
Alcoholism Definition

• ASAM "Alcoholism is a primary chronic disease
  characterized by impaired control over drinking,
  preoccupation with alcohol, use of alcohol
  despite adverse consequences, and distortions, in
  thinking, most notably denial.
• DSM IV Maladaptive pattern of substance use,
  leading to clinically significant impairment or
  distress, as manifested by 3 or more occurring
  within 12 month period.
• " a compulsion to drink alcohol, causing harm to
  self or others." (Lowinson)

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Alcohol Dependence Definition

• DSM IV Maladaptive pattern of substance use,
  leading to clinically significant impairment or
  distress, as manifested by 3 or more occurring
  within 12 month period.
• Tolerance
• Withdrawal
• Taken in larger amounts than intended
• Desire to cut down
• Time spent in activity to obtain
• Social/occupational/recreational activities
  reduced
• Continued use despite knowledge of
  persistent/recurrent problem

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Typology

• Q. A 35 year old male reports a 20 year history
  of excessive alcohol use. He is currently on
  probation for assault. He has one history of a
  suicide attempt at age 22, but no other
  psychiatric history. His father was a heavy
  drinker who was abusive while drinking and died
  of a liver-related illness at the age of 60.
  This history is most consistent with
• (A). Type I Alcoholism
• (B). Type II Alcoholism
• (C). Alcoholism and co-morbid Antisocial
  Personality Disorder
• (D). Primary Alcoholism and Secondary Affective
  Disorder
• (E). Primary Affective Disorder and Secondary
  Alcoholism

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Typology

• Unidimensional typology Winokur (1971) Primary
  and Secondary Alcoholics
• Onset of psychiatric symptoms
• Mutidimensional typology
• Cloninger, Type I and Type II
• Type I onset after 25, no criminality, ability
  to abstain for periods
• Low in novelty seeking, high in harm avoidance
• Type II onset before 25, recurrent severe
  medical consequences, male only
• High novelty seeking, low harm avoidance
• von Knorring Type I and Type II
• Type I onset after 25, no impulsivity
• Type II onset before 25, high rates of familial
  alcoholism, impulsivity, thrill seeking behavior
• Cluster analysis Babor, Type A and Type B

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Identification and Assessment

• Screening tools
• CAGE
• Cut down, Annoyed, Guilty, Eye opener
• MAST
• Michigan Alcohol Screening Test
• 25 questions, assess lifetime of drinking
  problems
• Assessment
• ASI Addiction Severity Index
• SCID
• History and PE, laboratory
• Sensitivity, but ask direct questions
• Ask for pattern of use
• Corroborate with SO
• Laboratory values should gGGT and MCV

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Treatments

• Treatment more effective than no treatment
• Pharmacotherapy
• Psychosocial treatments
• 12-Step
• Contingency Management
• Cognitive Behavioral
• Project Match

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Pharmacotherapy
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Pharmacotherapy

• Treat withdrawal
• Reduce consumption and craving
• Prevent relapse
• Treat psychiatric problems

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Alcohol Withdrawal

• Stage Onset Signs/Symptoms
• 1 8 hours mild tremor, anxiety, nausea
• 2 24 hours tremors, hyperactivity,
  insomnia,hallucinatory phenomena
• 3 24 hours same as 2 but more severe,
  seizures
• 4 2-5 days delirium tremens

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Detoxification Medical Management

• Nutritional support
• Psychosocial support
• Pharmacologic therapy
• Sedatives benzodiazepines
• Beta Blockers
• Adjuctive therapy
• Other
• Valproic acid,
• Tegretol
• Neurontin

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Strategies for Detoxification

• Symptom-triggered-Chlordiazepoxide (25-100mg)
  orally for symptoms
• Vital sign parameters
• CIWA scores (gt 8)
• Fixed-schedule dosing-Chlordiazepoxide orally
  (50-100mg), every 6 hours for 2-3 days, then
  decrease dose to 25-50 mg)
• Front-loading- Diazepam 10 or 20 mg orally every
  2h until sedated

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Detoxification

• Q. A 55 year old male with a history of heavy
  alcohol consumption for 30 years and multiple
  detoxs presents for treatment. After 2 days in
  an ambulatory detox setting, he reports seeing
  pink elephants. He is otherwise stable. This
  symptom is c/w which of the following
• DTs
• Alcoholic hallucinosis
• Korsakofs psychosis
• Wernickes encephalopathy
• Impeding withdrawal seizure.

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Naltrexone

• Oral opioid antagonist
• Preclinical trials show these agents decrease
  alcohol intake and preference
• 2 original trials establishing efficacy
  Volpicelli et al., 1992 OMalley et al., 1992.
• FDA approved for treatment of alcoholism.
• Subsequent laboratory studies may decrease the
  desire and high associated with alcohol intake.
• Recent multi-site study in veterans negative
  results

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Naltrexone

• Dose 50mg/day
• Prior to initiation, check LFTs
• Most common side effects nausea, headache,
  dizziness, insomnia, vomiting, anxiety and
  somnolence.
• Effective in conjunction with psychosocial
  treatment.

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Aversive Agents

• Disulfiram (Antabuse)
• Mechanism of Action Inhibits aldehhyde
  dehydrogenase
• Alcohol-disulfiram reaction flushing,
  palpitations, SOB, nausea and HA.
• Disulfiram has been shown to ? frequency of
  drinking but not augment abstinence (Fuller et
  al., 1986)

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Clinical use of Disulfiram

• Dose 250mg per day
• May increase to 500 mg
• Check LFTs prior to initiation
• Must be abstinent for 48 hours
• Most common side effects GI disturbance,
  headache, metallic taste in mouth, peripheral
  neuropathy
• Potential for alcohol-disulfiram reaction

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Acamprosate (CampralR)

• Synthetic derivative of homotaurine (analogue of
  GABA)
• Studies conducted in Europe,recently tested in
  USA
• ? dose-response effect
• May effect GABA system, excitatory AAs or opioid
  system

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Clinical use of Acamprosate

• Dose recommended- 2000 mg day in divided doses
• Recommended for post-detoxification
• Most common side effects abdominal pain,
  diarrhea, sexual side effects, confusion
• Used in conjunction with psychosocial counseling

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Other Medications

• Nalmefene
• Ondansetron
• Topiramate

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Other opioid antagonists

• Nalmefene
• Less liver toxic
• Stronger affinity for other receptors (d k)
• Only 1 clinical trial (Mason et al., 1999)
• Effective in preventing relapse to heavy drinking

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Serotonergic AgentsSSRIs

• SSRIs ? alcohol preference in laboratory animals
• SSRIs tested in heavy drinkers (include
  citalopram, fluoxetine, zimeledine, viqualine),
  small ? in alcohol consumption.
• Some studies showed early benefit of SSRIs, not
  sustained throughout treatment.
• Some studies have suggested a differential effect
  depending on classification of alcoholism (family
  hx positive, rate of alcohol consumption etc.)

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Serotonergic Agents

• 5-HT3 antagonists(ondansatron, tropisetron)
• Suppress DA release, block reward mechanism
• Laboratory studies equivocal, 1 small pilot study
  in alcohol dependent males negative
• New large trial suggests ondasatron effective in
  early onset
• 5-HT2 antagonists (ritanserin, amperoxide,
  risperidone)
• Laboratory, treatment and healthy subject studies
  negative
• 5-HT1A agonists (gepirone, ipsapirone etc)
• Equivocal animal studies
• Other (5hydroxytryptophan and other precursors)
• Laboratory and open label studies equivocal.

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Ondansetron

• 5-HT3 Rs Antagonist
• 1 Clinical Trial (Johnson et al., 2000)
• Double-blind, placebo controlled trial- 4 cells
  (3 doses ondansetron 1, 4 or 16 mg/kg and
  placebo)
• 12 weeks total (1 week placebo lead-in, 11 weeks
  tmt)
• CBT was standard psychotherapy
• Effective for early onset alcoholics
• Increased days abstinent
• Fewer drinks per drinking day, drinks per day
• 4 mg dose superior

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Topiramate

• Anti-epileptic, has effects on GABA
• Large 12-week trial conducted,
• Escalating doses 25mg-300mg
• Outcomes suggest, compared to placebo
• Fewer drinking days, drinks per drinking days
• Decrease craving
• Can initiate while still drinking?
• Better than naltrexone and acamprosate, but more
  SEs

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Dopaminergic Agents

• DA agonists and antagonists mixed results in
  human studies
• Bromocriptine no better than placebo in trials in
  reducing alcohol consumption
• Tiapride (DA antagonist), several promising
  European studies

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Psychosocial Treatments?

• Q. A 40 year old female has a history of drinking
  4 nights/week for 10 years. She presents to her
  ob-gyn for a routine physical. PE is
  unremarkable, LFTs are 3x normal. She has been
  married for 10 years, has no children and has a
  stable job. What is the next appropriate step in
  treatment?
• A. Referral to Motivational Enhancement Therapy
• B. Referral to AA
• C. Referral to Detoxification
• D. Physician Counseling/Advice
• E. Inpatient Rehabilitation

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Project Match

• Q. What is Project Match?
• (A.) A demonstration project with medical
  students involved in the Match.
• (B.) A single site study where patients are
  matched to a therapist based on demographic
  characteristics
• (C.) A pharmacotherapy study of matching
  depressed patients to SSRIs vs. TCAs on the
  basis of /- alcoholism.
• (D.) A multi-site stud evaluating the benefit of
  matching alcohol dependent individuals to 3
  different psychosocial tmts.

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Alcoholics Anonymous

• Q. Which of the following describes AA?
• (A.) Peer counseling?
• (B.) Self-help group?
• (C.) Client-centered therapy?
• (D.) Group therapy?

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Alcoholics Anonymous

• Founded in 1935
• Worldwide organization
• Does it work?
• Evidence points to yes
• Positive relationship between AA attendance and
  outcome

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Alcoholics Anonymous

• Q. Which of the following is a Step from AA?
• (A.) Anonymity is the spiritual foundation of all
  our traditions.
• (B.) The only requirement for AA membership is a
  desire to stop drinking.
• (C.) Made a searching and fearless moral
  inventory of ourselves.
• (D.) There is one ultimate authority, a loving
  God.

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AA and 12-Step Facilitation

• Difference between AA and 12-step facilitation
• Self-help vs therapy
• TSF includes
• Education and encouragement to attend AA
• Review of concepts from AA
• Encouragement to obtain sponsor etc.

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Cognitive Behavioral Treatments

• Relapse Prevention
• Relapse vs. lapse
• Seemingly irrelevant decisions
• Motivational Enhancement Therapy
• Externalize ambivalence about stopping
• Based on Stages of Change
• CBT vs CBI

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Contingency Management

• 3 Principles
• Frequently monitor behavior
• Provide tangible positive reinforcers
• Doses in methadone maintenance programs
• Vouchers, cash payments
• Prize approach
• Disability payments
• Remove the reinforcer when target behavior
  doesnt occur
• Criticized for being impractical
• Innovative use may help w/ some patients