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
Morphine dependence (DSM IV 304.0) Prevalence: : 0.6-0.9% 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
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...
Relapse Rates following treatment 70 50 40 45 Alcohol Opiates Cocaine Nicotine O Brien & McLellan, 1996, The Lancet
Relapse Rates Are Similar for Drug Dependence and Other Chronic Illnesses Percent of Patients Who Relapse 100 90 80 70 60 50 40 30 20 10 0 40 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.
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
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
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
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
Information about Austria (8 MIO inhabitants) 50 000 opioid dependent subjects 6 400 are in opioid maintenance treatment Vienna Vienna: : 1.8 mio inhabitants Around 25 000 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
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 30-40 Some 100 Few > 250
Ortner et al; EAR 2004; 10: 105-111; 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
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
Mean Dose of Buprenorphine 20 Addiction Clinic GPs 18 Buprenorphine (mg) 16 14 12 10 8 6 4 2 0 Week 01/d1 Week 01/d3 Week 02/d1 Week 03/d1 Week 05 Week 07 Week 11 Week 13
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
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??
Sees at al; 2000 Methadone maintenance therapy vs 180-day psychsocially enriched methadone detoxification for treatment of opioid dependence
1-year retention & social function after buprenorphine-assisted relapse prevention...: randomised, placebo-controlled controlled trial Kakoo, et al, The Lancet, 2003 4 people died in placebo controll Group (with psychosocial support)
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
State-of-the-art: Maintenance therapy with opioids Naltrexone Methadone Buprenorphine Buprenorphine/Naloxone Buprenorphine - Depot LAAM Oral slow-release Morphine Codeine Heroin
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
Molecule
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
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):223-33 33 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 16-16 16-24 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.
PET
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
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
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: 1090-1110, 1110, 2005
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
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)
Results: Cochrane review on opioid maintenance therapy (RCT) 12 075 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
Retention: LAAM/METHADONE/BUPRENORPHINE
Retention: LAAM/METHADON/BUPRENORPHIN - Naltrexon
LAAM
Levo-alpha-acethylmethadol acethylmethadol (LAAM) versus methdone: treatment retention and opiate use Longshore D, Annon J, Anglin MD, Rawson R Addiction 100: 1131-1139 1139 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
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
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: 231-239 239 Kraigher et al; Slow release morphine for the treatment of opioid dependence; ; EAR 2005; 11:145-151 151 Eder et al. Double-blind, blind, double-dummy dummy comparison of slow-release morphine and methadone, Addiction 2005; 100:1101-1109 1109 Is there a place?... yes
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
Clinical Expertise and Policy Context Research Evidence Patient Preference A model for evidence-based clinical decisions (from Haynes et al, 1996)
...and evidence-based medicine
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
No, Doc - this time I don`t want to have a prescription, I want to talk!