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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 The Spectrum of Use and Misuse Dependence Hazardous/Harmful Use/Substance Abuse Non-Hazardous Use Non-use ADTRU The Development of Substance Use Disorders Repeated use of: • alcohol • certain medications • drugs Development of a repetitive behaviour Hazardous / Harmful Use/ Substance Abuse ADTRU Mechanisms of Substance Dependence Repeated use of: • alcohol • certain medications • drugs Re-setting of dopamine reward centres Substance dependence syndrome ADTRU Alcohol’s Effects on Opioid Neurotransmission Dopaminergic neurone GABA Neurone Opioid (eg β endorphin) neurone Ventral tegmental area Nucleus accumbens 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 ADTRU Dependence and the Reinstatement Phenomenon } } ALCOHOL A FEW DAYS 5 - 10 YEARS INTAKE AND SEVERITY OF DEPENDENCE TIME 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. ADTRU Responses to Substance Misuse Tertiary intervention Brief intervention (Secondary prevention) Primary prevention ADTRU Rapid Assessment ADTRU Audit 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 4 4 or more times a week o 4 10 or more o 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 o 0 Never 1 or less 2 2 to 4 3 2 to 3 times a month 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 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 8. How often during the lst year have you been unable to remember what happened the night before because you had been drinking? o 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? o 0 No 2 Yes, but not in the 4 Yes, during the last last year year 10. Has a relative, a friend, a doctor or another health worker been concerned about your drinking or suggested you cut down? o 0 No 2 Yes, but not in the 4 Yes, during the last last year year RECORD TOTAL OF SPECIFIC ITEMS HERE ADTRU o 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 ADTRU Decision Tree Offer AUDIT questionnaire Review AUDIT score Non-hazardous range • Feedback, or no further action Hazardous or harmful range • • Feedback Brief intervention Alcohol dependent range • • • • Feedback Referral to specialist Need for detoxification? Pharmacotherapy ADTRU Brief Alcohol Intervention ADTRU What is Brief Alcohol Intervention? • 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 ADTRU Aims of Brief Alcohol Intervention • 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 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) ADTRU WHO Brief Intervention Study - findings from Australian Centre II 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 Saunders et al (1998) ADTRU WHO - RPAH Early Intervention Trial Results at nine months Average weekly alcohol intake (grams) Condition Intake at Recruitment Intake at Follow up % reduction Control 402 402 0 Simple advice 424 307 27.5 Advice and counselling 480 341 29.0 Extended counselling 460 285 38.0 ADTRU Aggregate Effect Sizes for Brief Intervention versus Control in Non-Treatment-Seeking Populations 1. Composite Outcome Follow-up period No. of Studies 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) 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 ADTRU Four-year Outcome after Brief Intervention Medical use (48-months postbaseline) Emergency department visits Days of hospitalization 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 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 * p < 0.10 ** p < 0.05 Treatment Control (n = 392) 302* 420** (n = 382) 376* 664** 0 20 67 25 169 2 31 72 25 177 8 8 2** 2 3 6 Fleming et al (2002) ADTRU 11 6 11** 1 3 9 Drink-less: getting started ADTRU The Drink-less Program -how it works Screening – Receptionist gives AUDIT questionnaire to patient – Patient brings questionnaire to consultation ADTRU ADTRU ADTRU 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 ADTRU ADTRU ADTRU The Treatment of Alcohol Dependence Alcohol Withdrawal SYNDROME Simple Complicated by fits Delirium Tremens TIME OF ONSET 6 - 48 hours 4 - 48 hours 48 hours - 7 days DURATION 24 hours - 5 days Usually single 3 - 10 days ADTRU Alcohol 2 Protocol - Regular Diazepam 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 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) ADTRU Acamprosate • 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 ADTRU Alcohol’s Actions on Glutamate Neurotransmission ADTRU Controlled trials of Acamprosate in Alcohol Dependence. II Authors Country No. Duration Outcome Abstinence Paille et al. (1995 ) France 538 1 year A: C: Sass et al. (1997) Germany 272 1 year 330 6 months A: C: A: C: A: C: A: C: Tempesta et al. (1998) Italy Besson et al. (1998) Switzerland 110 Ritson,Chick et al. (1999) U.K. 581 1 year 6 months % abstinent days Biochemistry 61% 47% 43% 21% 58% 45% 25% 5% 12% 11% 62% 45% 66% 54% 40% 21% Biological markers showed greater improvement in acamprosate group No difference No difference ADTRU Naltrexone • A specific antagonist of opioids • Introduced in Australia in 1999 for the treatment of alcohol dependence ADTRU Alcohol’s Effects on Opioid Neurotransmission Dopaminergic neurone GABA Neurone Opioid (eg ß endorphin) neurone Ventral tegmental area Nucleus accumbens ADTRU Controlled Trials of Naltrexone in Alcohol Dependence. I Authors Country No. Duration Outcome Abstinence O’Malley et al. (1992 ) USA 104 3 months Volpicelli et al. (1992) USA 70 3 months Chick et al. (1999) UK 175 3 months Anton et al. (1999) USA 131 3 months Morris et al. (2001) Australia 111 3 months N: C: N: C: N: C: N: C: 51% 23% 77% 46% 18% 19% 62% 40% N: C: 51% 25% Relapse free Biochemistry 69% 40% 79% 59% % with heavy drinking days less in those on naltrexone Improvement in those on naltrexone 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 ADTRU Combined Pharmacotherapies for Alcohol Dependence. I : Naltrexone and Acamprosate 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 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 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 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 ADTRU Buspirone • 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 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 ADTRU Treatments for Alcohol Misuse Best practice Bad practice Available Brief interventions Just say no! CBT MET 12 -step approaches Acamprosate Naltrexone (limited) (limited) 12-step approaches (limited, if at all) (limited) Analytic psychotherapy Confrontation therapy Supportive counselling Analytic psychotherapy Confrontation therapy Supportive counselling Aversion therapy Hypnosis Benzodiazepines (post-detox) Anti-depressants Benzodiazepines for detox and beyond Anti-depressants Residential treatment ADTRU Cost-effectiveness of Treatment for Hazardous Alcohol Use and Alcohol Dependence • 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 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 ADTRU