1 Addiction Pharmacotherapies in Integrated Systems OPIOIDS Univ. Prof. Dr.. Gabriele Fischer Department of Psychiatry Addiction clinic Medical University Vienna DELIVERY SYSTEMS FOR SUBSTANCE ABUSE TREATMENT Istanbul September 5th-7th, 2005
2 Morphine dependence (DSM IV 304.0) Prevalence: : % 0.9% in Europe (UNODC; 2004) 13 times higher mortality compared to a matched age-group group (predominantly young men) 75% Hepatitis C High comorbidity with affective disorders (> 50%) 25% are in a treatment system Women have a lower retention rate: Higher psychiatric comorbidity - mood disorders, PTSD Higher amount of opoid receptors Higher stigma Fluctuation of the staff Decision making: : male system
3 Addiction is a brain disease and it matters Science...The most effective treatment approach, as in many psychiatric diseases, includes biological, behavioral and social-context treatment approaches......addiction is a chronic relapsing disorder...
4 Relapse Rates following treatment Alcohol Opiates Cocaine Nicotine O Brien & McLellan, 1996, The Lancet
5 Relapse Rates Are Similar for Drug Dependence and Other Chronic Illnesses Percent of Patients Who Relapse to 60% Drug Dependence 30 to 50% Type I Diabetes 50 to 70% Hypertension 50 to 70% Asthma Source: McLellan, A.T. et al., JAMA, Vol 284(13), October 4, 2000.
6 Structure Office based prescription versus specialized clinics Why Maintenance in opioid dependence? Why detoxification? Why Methadone? Why some other opioid medication? Buprenorphine,, LAAM, SR-morphine
7 Specialist clinic Adolescents Pregnancy Advantages: multidisciplinary Psychiatrist Pharmacist Nurses Psychologist Social worker Disadvantages High treshold - selected group Centralized in large cities Limited capacity Expensive Stigma- addiction addiction clinic
8 General practitioner Advantages family doctor - prevention & early treatment initiation Low treshold More capacity Decentralized Cost effective Integration into mainstream Drug-drug interaction Disadvantages Limited psychiatric education - comorbidity Time for education Lack of support through specialised clinics
9 Modell: Vienna University/ General Hospital Vienna SPECIAL PROGRAMME: PREGNANCY, Adolecents Hepatitis, HIV Prison Local pharmacy Clinical pharmacist ADDICTION CLINIC visits: 1-7 times a week psychiatrists socialworkers psychologists nurses GP`S AKH: All inpatient with addiction
10 Information about Austria (8 MIO inhabitants) opioid dependent subjects are in opioid maintenance treatment Vienna Vienna: : 1.8 mio inhabitants Around opioid dependent subjects > 4000 in opioid maintenance: : 2/3 in GP`s offices All GP`s can prescribe opioids, who are registered for treatment 239 community pharmacies provide maintenance treatment Majority of opioid narcotic prescriptions are placed in pharmacies HIV/AIDS: around 9000 infected; ; total 2418 Aids pat. - died: : 1394
11 How many GP`s treat opiate addicts in Vienna Around 200 GP`s Per visit around 20 EURO Continious education - 4 times a year Few 2-3 Majority Some 100 Few > 250
12 Ortner et al; EAR 2004; 10: ; 111; Buprenorphine maintenance: office - based treatment with Addiction support Addiction Clinic GPs 100% 80% 60% 40% 20% 0% Induction Week 01 Week 02 Week 03 Week 05 Week 07 Week 09 Week 11 Week 13 Week 15
13 100% 80% 60% 40% 20% 0% Urinetoxicology Addiction Clinic GPs Week 01 Week 02 Week 03 Week 05 Week 09 Week 11 Week 15 Opiates p < 0,001 Cocaine p < 0,001 Benzodiazepines n.s. Induction % positive urinetoxicology
14 Mean Dose of Buprenorphine 20 Addiction Clinic GPs 18 Buprenorphine (mg) Week 01/d1 Week 01/d3 Week 02/d1 Week 03/d1 Week 05 Week 07 Week 11 Week 13
15 Organisation of maintenance treatment in the European Union General practitioner s: Austria, Belgium, France (buprenorphine( buprenorphine), Germany, Ireland, Luxembourg, UK Specialised centres: Denmark, France (methadone), Italy, the Netherlands, Portugal, Spain Specialised centre - limited number: Finland, Greece, Sweden, Norway New member states Specialised clinics - still in some countries monopol
16 Opiate detoxification: What are the goals? Charles O`Brian, Addiction 100:1035; 2005 Ultra-rapid, rapid, rapid, intermediate and long-term detoxification Different medication methadone, clonidine, lofexidine,, morphine, neuroleptics, buprenorphine, buprenorphine/naloxone psychosocial support??
17 Sees at al; 2000 Methadone maintenance therapy vs 180-day psychsocially enriched methadone detoxification for treatment of opioid dependence
18 1-year retention & social function after buprenorphine-assisted relapse prevention...: randomised, placebo-controlled controlled trial Kakoo, et al, The Lancet, people died in placebo controll Group (with psychosocial support)
19 Relapse and mortality after opioid detoxification Strang et al., BMJ 2003 High Mortality: Patients, who finished successfully 28 day detoxification Patients, who remained longer in-patient High comorbidity After prison discharge Who survived? Patients who discontinued detoxification treatment
20 State-of-the-art: Maintenance therapy with opioids Naltrexone Methadone Buprenorphine Buprenorphine/Naloxone Buprenorphine - Depot LAAM Oral slow-release Morphine Codeine Heroin
21 intake Methadone: Treatment works Vincent Dole, 1965 Mu-agonist Plasma half-life: 24 hours BUT: poor metabolizers fast metabolizers concomitant medication - racemic version - Solutions for daily supervised
24 Buprenorphine: will it succeed? Pharmacological advantages Safety, efficacy and long duration of action - up to 72 hours Clinical advantages High patients acceptance, low abuse potential Logistic advantages Multiple settings of delivery Political and social congruence
25 A contolled trial of daily versus thrice-weekly buprenorphine admnistration for the treatment of opiate dependence Perez de los Cobos J et.al., Spain Drug and Alcohol Dependence (2000) 59(3): Design: double-blind, blind, double- dummy,, parallel 12 week-trial (n = 60) daily n=30, thrice-weekly n=30) Retention: daily dosing 88 % thrice-weekly 82 % Final doses: 8 mg/ daily mg/ thrice-weekly buprenorpine Opioid urinalysis: pos.. 58,5 % thrice-weekly vs.. 46,6 % daily administration Result: Both design are equivalent in retention, but significant lower opioid pos. urinetoxicology in daily intake of buprenorphine.
27 Buprenorphine literature search US/Europe/Australia There are differences: Up 2001 all US publications refer to buprenorphine applied in a solution - the registered substance is - a sublingual tablet - different bioavailability
28 Therapy of opioid dependence in GP`s offices NEJM, 2002: Fiellin et al: Office - based treatment with buprenorphine NEJM, 2003: Fudala et al, 2003: Office based treatment of opiate addiction with buprenorphine- naloxone
29 BUPRENORPHINE/ NALOXONE FOR MAINTENANCE & DETOXIFICATION THERAPY SUBOXONE : Sublingualtablets Buprenorphine : Naloxone: Ratio 2 mg: 0.5 mg Ratio 8 mg: 2 mg Ling W., et al: National Institute on Drug Abuse Clinical Trial Network Addiction 100: , 1110, 2005
30 Buprenorphine-Depot Evaluation of an injecting depot formulation of buprenorphine: placebo comparison; Sigmon et al., 2004 Addiction Depot formulations: : will pharmacological advances improve treatment options and outcomes for substance abusers? Petry, Addiction 2004 Controversial discussion
31 Cochrane reviews on opioid maintenance therapy (RCT) Clark et al: 2003, Faggiano et al: 2003, Ferri et al: 2003 Mattick et al: 2003, Mattick et al: 2004 Out come parameter 1. Retentionrate 2. Concomitant consumption (heroin, cocaine, benzodiazepine)
32 Results: Cochrane review on opioid maintenance therapy (RCT) Participants, mean length: : 32 weeks; Meth & Bup & LAAM 32 USA, 13 Europe, 5 Australia,, 2 Asia Methadone Is the most effective substance in regard to retention and reduced concomitant consumption of heroin Higher dosing provides better outcome
33 Retention: LAAM/METHADONE/BUPRENORPHINE
34 Retention: LAAM/METHADON/BUPRENORPHIN - Naltrexon
36 Levo-alpha-acethylmethadol acethylmethadol (LAAM) versus methdone: treatment retention and opiate use Longshore D, Annon J, Anglin MD, Rawson R Addiction 100: No difference in treatment retention (75,5% vs 77%) after 26 weeks (mean dosing: : LAAM: 77.5 mg, M: 67,4 mg LAAM patients tested less likley positive for opiates in urinalysis No adverse events No cardiological SAE were observed with LAAM
37 Oral-slow release morphine Capsules with small pellets Tablets Duration of action: : 24 hours onset of action: after 1,5 hours Peak: after 6 hours Registered medication in Austria since 1999
38 Oral slow-release Morphine Mitchell et al, DAD, 2003;... Oral slow-release for maintenance... Fischer et al. Oral slow release morphine in pregnant opioid addicts; Addiction 1999; 94: Kraigher et al; Slow release morphine for the treatment of opioid dependence; ; EAR 2005; 11: Eder et al. Double-blind, blind, double-dummy dummy comparison of slow-release morphine and methadone, Addiction 2005; 100: Is there a place?... yes
39 Heroin: yes or no? Rehm et al., The Lancet 2001: Feasibility, safety and efficacy of injectable heroin prescription for refratory opioid addicts: Van den Brink et al., BMJ 2003: Medical prescription of heroin to chronic, treatment resistent heroin dependent patients: two randomized trials. Yes, treatment shows safety & efficacy for a defined group of patients
40 Clinical Expertise and Policy Context Research Evidence Patient Preference A model for evidence-based clinical decisions (from Haynes et al, 1996)
41 ...and evidence-based medicine
42 CONCLUSION Individual needs in different countries: legislation education financial support Research-treatment Ideal dosing Comorbidity Expand treatment To establish a way between laissez-faire and overregulation
43 No, Doc - this time I don`t want to have a prescription, I want to talk!