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Medical issues about Methadone : What the counselor needs to know Judith Martin, MD Medical Director The 14th Street Clinic, Oakland, CA www.14thstreetclinic.org Counseling Staff THE DOSING WINDOW Epidemiology Opioid dependence Office of National Drug Control Policy (1999) 810,000 persons Only 170,000 receiving medication treatment Cost $20 billion per year total costs (NIDA 1992) $9.6 billion spent on heroin (ONDCP 1988-1995) $1.2 billion per year health care costs (NIDA 1992) Prescription opioid abuse epidemiology Prescription opioid use (2001), ED reports: 90,000+ (DAWN) Reports of oxycodone abuse:18,000+ Reports hydrocodone abuse: 21,000+ Reports methadone abuse: 10,000+ 1994- 2002, oxycodone 450% increase! Bottom line: big street value! Number of new nonmedical users of therapeutics (NSDUH, 2002) Commonly Abused Opioids Diacetylmorphine (Heroin) Hydromorphone (Dilaudid) Oxycodone (OxyContin, Percodan, Percocet, Tylox) Meperidine (Demerol) Hydrocodone (Lortab, Vicodin) Commonly Abused Opioids (continued) Morphine (MS Contin, Oramorph) Fentanyl (Sublimaze) Propoxyphene (Darvon) Methadone (Dolophine) Codeine Opium Route of heroin administration Treatment Entry Data System 1992-1997 100% 75% 50% 25% 0% 1992 1993 1994 1995 1996 1997 Injection Inhalation Smoking Other Four questions patients ask: How is methadone better for me than heroin? What is the right dose of methadone for me? How long should I stay on methadone? What are the side effects of methadone? Talking to patients about addiction treatment models Medical Recovery Psychodynamic Spiritual Behavioral ADDICTION AS A CHRONIC ILLNESS Chronic relapsing condition which untreated may lead to severe complications and death. ADDICTION AS CHRONIC DISEASE: IMPLICATIONS It is treatable but not curable. Adjustment to diagnosis is part of patient’s task. There is a wide spectrum of severity. Retention in treatment is key. Best treatment is integrated. Four questions patients ask: • How is methadone better for me than heroin? • What is the right dose of methadone for me? • How long should I stay on methadone? • What are the side effects of methadone? How is methadone better than heroin? Legal Avoids needles Known amount ingested Opiate effects, physical Predictable physical effects of administering opiates: Tolerance: the body becomes efficient in processing the drug and requires ever higher doses to produce the desired effect. Dependence: when the drug is discontinued there are typical withdrawal signs and symptoms. IDU, pattern of heroin injection over 3 days Dose Response Methadone Simulated 24 Hr. Dose/Response At steady-state in tolerant patient “Loaded” “High” “Abnormal Normality” Normal Range “Comfort Zone” Subjective “Sick” w/d Objective w/d 0 hrs. Time Opioid Agonist Treatment of Addiction - Payte - 1998 24 hrs. How is methadone better than heroin? • • • • • Legal Avoids needles Known amount ingested Slow onset: no “rush” Long acting: can maintain “comfort” or normal brain function • Stabilized physiology, hormones, tolerance Four questions patients ask: • How is methadone better for me than heroin? • What is the right dose of methadone for me? • How long should I stay on methadone? • What are the side effects of methadone? Dose Response Methadone Simulated 24 Hr. Dose/Response At steady-state in tolerant patient “Loaded” “High” “Abnormal Normality” Normal Range “Comfort Zone” Subjective trough “Sick” w/d Objective w/d 0 hrs. Time Opioid Agonist Treatment of Addiction - Payte - 1998 24 hrs. What is the right dose? Eliminate physical withdrawal Eliminate ‘craving’ Comfort/function: usually trough is 400600 ng/ml, peak no more than twice the trough. Not oversedated Blocking dose “How Much???? Enough!!!” Tom Payte, MD Recent Heroin Use by Current Methadone Dose % Heroin Use 100 80 60 40 20 0 0 10 20 30 40 50 60 70 Methadone Dose, in mg. Ref: J. C. Ball, November 18, 1988 Slide adapted from Tom Payte 80 90 100 Four questions patients ask: • How is methadone better for me than heroin? • What is the right dose of methadone for me? • How long should I stay on methadone? • What are the side effects of methadone? Relapse to IV drug use after MMT 105 male patients who left treatment Percent IV Users 100 82.1 80 72.2 60 57.6 45.5 40 28.9 20 0 IN 1 to 3 Treatment 4 to 6 7 to 9 10 to 12 Months Since Stopping Treatment Adapted from Ball & Ross - The Effectiveness of Methadone Maintenance Treatment, 1991 Opioid Agonist Treatment of Addiction - Payte - 1998 “How Long??? Long Enough!!” Tom Payte, MD Four questions patients ask: • How is methadone better for me than heroin? • What is the right dose of methadone for me? • How long should I stay on methadone? • What are the side effects of methadone? Side effects of methadone: General opiate effects: Sedation/stimulation Maintained phys. dependence (stable) hypogonadism (not as severe as with heroin, may be dose dependent) Constipation Slight QTc prolongation on ECG (Martell etal) Sweating Methadone treatment tied to regulated clinic Treatment Outcome Data 8-10 fold reduction in death rate reduction of drug use reduction of criminal activity engagement in socially productive roles reduced spread of HIV excellent retention Crime among 491 patients before and during MMT at 6 programs Crime Days Per Year 300 250 200 Before TX During TX 150 100 50 0 A B C D E F Adapted from Ball & Ross - The Effectiveness of Methadone Maintenance Treatment, 1991 Opioid Agonist Treatment of Addiction - Payte - 1998 HIV CONVERSION IN TREATMENT 35% 30% 25% 20% IT OT 15% 10% 5% 0% Base line 6 Month 12 Month 18 Month HIV infection rates by baseline treatment status. In treatment (IT) n=138, not in treatment (OT) n=88 Source: Metzger, D. et. al. J of AIDS 6:1993. p.1052 Opioid Maintenance Pharmacotherapy - A Course for Clinicians - 1997 A FEW WORDS ABOUT BUPRENORPHINE “Ceiling effect” and safety Displaced other opiates: withdrawal on induction Less agonist strength Schedule 3(methadone is 2) One form combined with naloxone Office – based use available Partial vs Full Opiate Mu Agonis death Opiate Effect Full Agonist (e.g., methadone) Partial Agonist (e.g. buprenorphine) Dose of Opiate Credit: Don Wesson, MD Percent Retained Buprenorphine, Methadone, LAAM: Treatment Retention 100 80 73% Hi Meth 60 58% Bup 40 53% LAAM 20 20% Lo Meth 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Johnson et al, 2000 Study Week Buprenorphine, Methadone, LAAM: Opioid Urine Results 100 All Subjects Mean % Negative 80 LAAM 49% 60 Bup Hi Meth 40% 40 39% Lo Meth 20 19% 0 1 3 5 7 9 11 Study Week 13 15 17 Effect of counseling in buprenorphine treatment (Fiellin, 2002) Opioid positive urines 1 0.8 MM MM+DC 0.6 0.4 0.2 0 Induction week 2-4 week 5-7 week 8-10 Remaining in treatment (nr) Retention in treatment Kakko et al, 2003, 20 15 10 Control, 6-day detox 5 Buprenorphine maintenance 0 0 50 100 150 200 250 Treatment duration (days) 300 350 Pharmacotherapy in context: correct glossary Abstinence includes pharmacotherapy Maintenance, not substituion or replacement (new term also: MAT) Tapering from maintenance, not detoxification, (also ‘medically supervised withdrawal’, or MSW) Discontinuation, not discharge Toxicology screens: pos/neg, not clean/dirty) Opioid pharmacotherapy, summary: Methadone, buprenorphine and LAAM all approved by the FDA for treatment of opiate dependence. (LAAM not currently available from any drug company) Best evidence so far supports maintenance. Detoxification attempts should have maintenance as a back up in case of relapse.