1. 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

2. ADTRU The Spectrum of Use and Misuse Dependence Hazardous/Harmful Use/Substance Abuse Non-Hazardous Use Non-use

3. ADTRU The Development of Substance Use Disorders Repeated use of: alcohol certain medications drugs Development of a repetitive behaviour Hazardous / Harmful Use/ Substance Abuse

4. ADTRU Mechanisms of Substance Dependence Repeated use of: alcohol certain medications drugs Re-setting of dopamine reward centres Substance dependence syndrome

5. ADTRU Alcohol’s Effects on Opioid Neurotransmission Opioid (eg β endorphin) neurone Dopaminergic neurone Nucleus accumbens Ventral tegmental area GABA Neurone

6. ADTRU The Dependence Syndrome A 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

7. ADTRU 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 DAYS ALCOHOL INTAKE AND SEVERITY OF DEPENDENCE } } TIME 5 - 10 YEARS

8. ADTRU Responses to Substance Misuse Tertiary intervention Brief intervention (Secondary prevention) Primary prevention

9. ADTRU Rapid Assessment

10. ADTRU Audit No 2 Yes, but not in the last year 4 Yes, during the last year o 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 year 4 Yes, during the last year o 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 o 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 o 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 o 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 o 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 o 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 o 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 o 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 o 9. Have you or someone else been injured as a result of your drinking? 0 RECORD TOTAL OF SPECIFIC ITEMS HERE o

11. ADTRU Interpretation of the AUDIT Score 0Abstainer 1-7Non-hazardous “safe” drinking 8-12Hazardous or harmful alcohol use 13+ High risk of alcohol dependence

12. ADTRU 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

13. ADTRU Brief Alcohol Intervention

14. ADTRU 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?

15. ADTRU 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

16. ADTRU 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)

17. ADTRU 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)

18. ADTRU WHO - RPAH Early Intervention Trial Results at nine months Average weekly alcohol intake (grams) ConditionIntake atIntake at% reduction RecruitmentFollow up Control 402 402 0 Simple advice 424 307 27.5 Advice and 480 341 29.0 counselling Extended 460 285 38.0 counselling

19. ADTRU Aggregate Effect Sizes for Brief Intervention versus Control in Non-Treatment-Seeking Populations Moyer et al (2002)

20. ADTRU 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

21. ADTRU Four-year Outcome after Brief Intervention Fleming et al (2002)

22. ADTRU Drink-less: getting started

23. The Drink-less Program -how it works  Screening – Receptionist gives AUDIT questionnaire to patient – Patient brings questionnaire to consultation

25. ADTRU

28. 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

29. ADTRU

31. The Treatment of Alcohol Dependence

32. ADTRU Alcohol Withdrawal SYNDROME TIME OF ONSET DURATION Simple 6 - 48 hours 24 hours - 5 days Complicated 4 - 48 hours Usually single by fits Delirium Tremens 48 hours - 7 days 3 - 10 days

33. ADTRU Alcohol 2 Protocol - Regular Diazepam

34. ADTRU 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)

35. ADTRU A derivative of the amino-acid, taurine. Chemically calcium bis acetyl homotaurine Complex pharmacological actions Interacts with the GABA A receptor, facilitating GABAergic inhibitory neurotransmission Inhibits glutamate excitatory neurotransmission by interacting with NMDA glutamate receptor Acamprosate

36. ADTRU Alcohol’s Actions on Glutamate Neurotransmission

37. ADTRU AuthorsCountry No. DurationOutcome 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

38. ADTRU Naltrexone A specific antagonist of opioids Introduced in Australia in 1999 for the treatment of alcohol dependence

39. ADTRU Alcohol’s Effects on Opioid Neurotransmission Opioid (eg ß endorphin) neurone Dopaminergic neurone Nucleus accumbens Ventral tegmental area GABA Neurone

40. ADTRU Controlled Trials of Naltrexone in Alcohol Dependence. I AuthorsCountry No. DurationOutcome 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

41. ADTRU Combined Pharmacotherapies for Alcohol Dependence. I : Naltrexone and Acamprosate Kiefer 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

42. ADTRU 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

43. ADTRU 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

44. ADTRU 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

45. ADTRU 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

46. ADTRU Buspirone A 5HT IA 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

47. ADTRU 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

48. ADTRU Treatments for Alcohol Misuse Best practiceBad practiceAvailable Brief interventionsJust say no! CBT (limited) MET (limited) 12 -step approaches 12-step approaches Acamprosate(limited, if at all) Naltrexone(limited) Analytic psychotherapy Confrontation therapySupportive counselling Aversion therapy Hypnosis Benzodiazepines Benzodiazepines (post-detox) for detox and beyond Anti-depressantsAnti-depressants Residential treatment

49. ADTRU 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

50. ADTRU 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