Alcohol Interventions : Successful and Innovative Intervention

Strategies

John B Saunders MD, FRACP

Professor of Alcohol and Drug Studies, University of Queensland,

Director, Alcohol and Drug Service, Royal Brisbane

and Women’s Hospital, Queensland Health,

Co-Director, WHO Collaborating Centre on Substance Misuse and Mental Health; Member, Australian National Council on Drugs

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The Spectrum of Use and Misuse

The Spectrum of Use and Misuse

Dependence

Hazardous/HarmfulUse/SubstanceAbuse

Non-Hazardous Use

Non-use

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The Development of Substance Use Disorders

Repeated use of:• alcohol• certain medications• drugs

Development of a repetitive behaviour

Hazardous / Harmful Use/ Substance

Abuse

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Mechanisms of Substance Dependence

Repeated use of:• alcohol• certain medications• drugs

Re-setting of dopamine reward

centres

Substance

dependence

syndrome

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Alcohol’s Effects on Opioid Neurotransmission

Opioid (eg β endorphin)

neurone

Dopaminergic neurone

Nucleus accumbens

Ventral tegmental

area

GABA Neurone

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The Dependence SyndromeThe Dependence SyndromeA psychobiological syndrome - a powerful internal

driving force. Features of the dependence syndrome:• impaired control over substance use• a strong desire to take the particular substance• preoccupation with substance use (given greater

priority than other activities)• increased tolerance• withdrawal symptoms on cessation of substance

use, or relief of withdrawal symptoms by further use

• continuation of use despite harmful effects

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Dependence and the Reinstatement Phenomenon

Dependence and the Reinstatement Phenomenon

Implications

If a person is physically dependent on alcohol to the extent that they

repeatedly (>twice per week) suffer withdrawal symptoms, he/she is

best advised to abstain rather than attempt moderated or controlled

drinking.

A FEW DAYSALCOHOL

INTAKE

AND

SEVERITY

OF

DEPENDENCE

}}TIME

5 - 10 YEARS

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Responses to Substance MisuseResponses to Substance Misuse

Tertiary

interventionBrief intervention

(Secondary prevention)

Primary prevention

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Rapid Assessment

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Audit

No 2 Yes, but not in the last year

4 Yes, during the last year

10. Has a relative, a friend, a doctor or another health worker been concerned about your drinking or suggested you cut down? 0 No 2 Yes, but not in the

last year4 Yes, during the last year

Select from the answers below and place the number that corresponds with your answer in the box

1. How often do you have a drink containing alcohol? Score

0 Never 1 or less 2 2 to 4 times a month

3 2 to 3 times a week

4 4 or more times a week

2. How many standard drinks do you have on a typical day when you are drinking? 0 1 or 2 1 2 to 4 2 5 or 6 3 7, 8 or 9 4 10 or more

3. How often do you have six or more drinks in one occasion? 0 Never 1 Less than monthly 2 Monthly 3 Weekly 4 Daily or almost daily

4. How often during the last year have you found that you were not able to stop drinking once you had started? 0 Never 1 Less than monthly 2 Monthly 3 Weekly 4 Daily or almost daily

5. How often during the last year have you failed to do what was normally expected from you because of drinking? 0 Never 1 Less than monthly 2 Monthly 3 Weekly 4 Daily or almost daily

6. How often during the last year have you needed a first drink in the morning to get yourself going after a heavy drinking session?

0 Never 1 Less than monthly 2 Monthly 3 Weekly 4 Daily or almost daily

7. How often during the last year have you had a feeling of guilt or remorse after drinking? 0 Never 1 Less than monthly 2 Monthly 3 Weekly 4 Daily or almost daily

8. How often during the lst year have you been unable to remember what happened the night before because you had been drinking?

0 Never 1 Less than monthly 2 Monthly 3 Weekly 4 Daily or almost daily

9. Have you or someone else been injured as a result of your drinking? 0

RECORD TOTAL OF SPECIFIC ITEMS HERE

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Interpretation of the AUDIT Score

0 Abstainer

1-7 Non-hazardous

“safe” drinking

8-12 Hazardous or

harmful alcohol use

13+ High risk of alcohol dependence

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Decision Tree

Offer AUDIT questionnaire

Review AUDIT score

Non-hazardous

range

Hazardous or

harmful range

Alcohol dependent

range

• Feedback, or no further action

• Feedback

• Brief intervention

• Feedback• Referral to specialist• Need for detoxification?• Pharmacotherapy

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Brief Alcohol Intervention

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• A brief and flexible form of therapy, comprising advice to reduce hazardous alcohol consumption and brief strategies to achieve this

• Ranges from 4 - 5 minutes to 2 - 3 sessions of up to 30 - 60 minutes

• Appropriate for people with hazardous alcohol use and a range of common mental health disorders

• Can complement other treatments for people who have an alcohol dependence syndrome

What is Brief Alcohol Intervention?

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• Advice is usually to reduce drinking, rather than abstinence

• Aims to prevent exacerbation of drinking and alcohol-related harm and progression to dependence

• Can complement the treatment of alcohol dependence but is not appropriate as the sole treatment

Aims of Brief Alcohol Intervention

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WHO Brief Intervention Study - findings from Australian Centre I

Aim: To determine the effectiveness of three types of brief intervention to assist persons with hazardous or harmful alcohol consumption reduce their intake and risk of harm

Design: Controlled clinical trial with random assignment to:

(1) No treatment control

(2) Simple advice (5 minutes and leaflet)

(3) Advice and brief counselling (20 minutes + manual)

(4) Advice and extended counselling (40 minutes over 2 - 3 sessions)

Saunders et al (1998)

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Subjects: Males and females aged 17 - 70 years, fulfilling mean intake or binge drinking criteria

Settings: General practice, general outpatient clinics, health screening programs

Follow Up: at 9 months, 2 years and 10 years

Measures: Average weekly alcohol intake, frequency of drinking to intoxication, occurrence of hazardous drinking, alcohol-related problems score, laboratory test results

Evaluation: By repeated measures analysis of variance and regression modelling

WHO Brief Intervention Study - findings from Australian Centre II

Saunders et al (1998)

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WHO - RPAH Early Intervention TrialResults at nine months

Average weekly alcohol intake (grams)

Condition Intake at Intake at % reduction

Recruitment Follow up

Control 402 402 0

Simple advice 424 307 27.5

Advice and 480 341 29.0counselling

Extended 460 285 38.0counselling

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Aggregate Effect Sizes for Brief Intervention versus Control in Non-Treatment-Seeking

Populations

1. Composite Outcome

Follow-upperiod

No. ofStudies

Effect Size Heterogeneity (Q)

< 3 months 4 0.30* 4.5

3 – 6 months 11 0.14* 10.6

6 – 12 months 23 0.24* 30.6

> 12 months 5 0.13# 7.4

* P < 0.01 # P = 0.05 Moyer et al (2002)

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Conclusions for Meta-analyses

• Brief interventions lead to a reduction in hazardous alcohol use, alcohol-related problems and biochemical abnormalities for at least 12 months

• No differential response according to gender or age

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Four-year Outcome after Brief Intervention

Fleming et al (2002)

Treatment Control

Medical use (48-months postbaseline) Emergency department visits Days of hospitalization

(n = 392)302*420**

(n = 382)376*664**

Motor vehicle events (48-months postbaseline) Motor vehicle crash with fatality Motor vehicle crash with non-fatal injuries Motor vehicle crash with property damage only Operating while intoxicated Other moving violations

0 20 67 25169

2 31 72 25177

Legal events (48-months postbaseline) Assault/Battery/Child abuse Resist/Obstruct officer/Disorderly conduct Controlled substance/Liquor violation Criminal damage/Property damage Theft/Robbery Other arrests

8 8 2** 2 3 6

11 6 11** 1 3 9

* p < 0.10** p < 0.05

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Drink-less: getting started

The Drink-less Program -how it works

Screening

– Receptionist gives AUDIT questionnaire to patient

– Patient brings questionnaire to consultation

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NSW Alcohol Interlock Program• Voluntary means of reducing a lengthy

disqualification• Combines brief alcohol intervention and fitting

an interlock device to the motor vehicle• Operates on a ‘user pays’ basis • Interlock Driver Licence holders are subject to a

BAC < 0.02 • Failure to comply with requirements of Program

results in loss of licence

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The Treatment of Alcohol Dependence

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Alcohol Withdrawal

SYNDROME TIME OF ONSET DURATION

Simple 6 - 48 hours 24 hours - 5 days

Complicated 4 - 48 hours Usually singleby fits

Delirium Tremens 48 hours - 7 days 3 - 10 days

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6 am 12 md 6 pm 12 mn

Day 1 10 mg 10 mg 10 mg 10 mg

Day 2 10 mg 10 mg 10 mg 10 mg

Day 3 5 mg 5 mg 5 mg 10 mg

Day 4 5 mg 5 mg 5 mg 10 mg

Day 5 Nil 5 mg Nil 5 mg

Alcohol 2 Protocol - Regular Diazepam

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Pharmacotherapies for Alcohol Dependence

• Acamprosate (Campral)• Naltrexone (Revia)• Disulfiram (Antabuse)• Topiramate• Ondansetron• Buspirone (for alcohol dependence and

comorbid social anxiety)• SSRIs (for underlying or residual depression)

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• A derivative of the amino-acid, taurine. Chemically calcium bis acetyl homotaurine

• Complex pharmacological actions

• Interacts with the GABAA receptor, facilitating GABAergic inhibitory neurotransmission

• Inhibits glutamate excitatory neurotransmission by interacting with NMDA glutamate receptor

AcamprosateAcamprosate

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Alcohol’s Actions on Glutamate

Neurotransmission

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Authors Country No. Duration Outcome

Abstinence % abstinent days Biochemistry

Paille et al. (1995 ) France 538 1 year A: 61% Biological markers

C: 47% showed greater

improvement in acamprosate group

Sass et al. (1997) Germany 272 1 year A: 43% 62%

C: 21% 45%

Tempesta et al. (1998) Italy 330 6 months A: 58% 66% No difference

C: 45% 54%

Besson et al. (1998) Switzerland 110 1 year A: 25% 40%

C: 5% 21%

Ritson,Chick et al. U.K. 581 6 months A: 12% No difference

(1999) C: 11%

Controlled trials of Acamprosate in Alcohol

Dependence. II

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Naltrexone

• A specific antagonist of opioids

• Introduced in Australia in 1999 for the treatment of alcohol dependence

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Alcohol’s Effects on Opioid Neurotransmission

Opioid (eg ß endorphin)

neurone

Dopaminergic neurone

Nucleus accumbens

Ventral tegmental

area

GABA Neurone

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Controlled Trials of Naltrexone in Alcohol

Dependence. IAuthors Country No. Duration Outcome

Abstinence Relapse free Biochemistry

O’Malley et al. (1992 ) USA 104 3 months N: 51% 69%

C: 23% 40%

Volpicelli et al. (1992) USA 70 3 months N: 77% 79%

C: 46% 59%

Chick et al. (1999) UK 175 3 months N: 18%

C: 19%

Anton et al. (1999) USA 131 3 months N: 62% % with heavy

C: 40% drinking days less

in those on naltrexone

Morris et al. (2001) Australia 111 3 months N: 51% Improvement in those

C: 25% on naltrexone

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Combined Pharmacotherapies for Alcohol Dependence. I :

Naltrexone and AcamprosateKiefer et al (2003) Study• Randomised, controlled trial of 160 alcohol dependent patients• Assigned, following detoxification, to one of four treatments

– placebo drug– naltrexone – acamprosate – naltrexone + acamprosate

• In addition, participants were encouraged to attend group therapy in a clinic setting

• Follow up at weekly intervals for three months

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Results of Kiefer et al (2003) Study

As judged by time to first drink and time to relapse, • Naltrexone was superior to placebo• Acamprosate was superior to placebo• Combination of naltrexone and acamprosate was

superior to acamprosate alone• There was a trend for of naltrexone and acamprosate

combined to be superior to naltrexone alone

Combined Pharmacotherapies for Alcohol Dependence. I :

Naltrexone and Acamprosate

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Alcohol-sensitising Drugs

• Aldehyde dehydrogenase inhibitors

Examples - disulfiram (“Antabuse”) 250 - 500mg daily• Result in an unpleasant flush reaction when alcohol is taken• Indications:

- alcohol dependence

- accepts goal of abstinence

- need for external aid to abstinence

- high risk situations for drinking imminent• Controlled trials indicate the abstinence rate is higher in the first

3-6 months when patients take these drugs• Best results are when given under supervision with contingency

management strategies

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Topiramate in the Treatment of Alcohol Dependence

• Inhibits glutamate hypersensitivity and facilitates GABAergic function

• 150 patients assigned to either topiramate or placebo

• Greater reduction in quantity and intensity of alcohol consumption compared with placebo

• Reduction in GGT in topiramate-treated group compared with placebo Johnson

et al., 2003

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Ondansetron• Early indications that ondansetron may be a

useful treatment for early-onset alcohol dependence (likely to be those with a positive family history)

• No support for its use in later onset alcohol dependence

• More evidence needed from controlled trials

• Not approved for the treatment of alcohol dependence in Australia

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BuspironeBuspirone

• A 5HTIA partial agonist

• An anti-anxiety drug

• Shown in some small-scale trials to increase cumulative days of abstinence in people with alcohol dependence and comorbid social anxiety compared with placebo

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SSRIs• Trialled (with high hopes) in the 1980s

• Reduce alcohol consumption by 20% in low dependence drinkers, but effect wears off after 1-2 months

• Do not increase abstinence rates in alcohol dependent people

• No change in overall alcohol intake in alcohol dependent people

• Reserved for patients with persistent depression after detoxification

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Treatments for Alcohol MisuseBest practice Bad practice Available

Brief interventions Just say no!

CBT (limited)

MET (limited)

12 -step approaches 12-step approaches

Acamprosate (limited, if at all)

Naltrexone (limited)

Analytic psychotherapy Analytic psychotherapy

Confrontation therapy Confrontation therapy

Supportive counselling Supportive counselling

Aversion therapy

Hypnosis

Benzodiazepines Benzodiazepines (post-detox) for detox and beyond

Anti-depressants Anti-depressants Residential treatment

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• Cost-effectiveness of brief alcohol interventions:

$3 to $7 return for each $1 invested

• Cost-effectiveness of treatment for alcohol dependence:

$4 to $5 return for each $1 invested

Cost-effectiveness of Treatment

for Hazardous Alcohol Use and Alcohol Dependence

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Treatments for Alcohol Misuse: Looking to the Future

• Correspondence-based, CD-ROM and Internet therapies

• Combined CBT/motivational therapy and pharmacotherapy

• Combined pharmacotherapies

Acamprosate and naltrexone

Acamprosate and disulfiram

Naltrexone and ondansetron• Depot preparations