Methadone and opioid use and misuse.

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Methadone and opioid use and misuse.

• Monitoring MOA
• Spring Training
• 2010

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Who is speaking?

• ACOFP board certified primary care physician
• Family Medicine educator (Synergy Medical)
• Joint appointment to Dept. of Psychiatry
• Credentials in Pain and Addiction
• Credentials in Forensics/Deputy Med Examiner
• Armed Forces Institute of Pathology
• Masters Tox/Pharm U. Missouri at KC/Pharm
• Active pain consultant Hospice Director
• Activist, advocate addictionologist

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Conflict of Interest

• Speakers Bureau Rickett Benckiser, Inc.
• HealthPlus pays me to speak on mental health at
  1-2 CME events per year.
• Employee at Hospice of Michigan.
• Special Consulting AOAAM consultant at the
  White House Office of National Drug Control
  Policy (ONDCP) September 2009.

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• OBJECTIVES
• 1. Evaluate the REMS epidemiology opiates for
  pain, opiate abuse and unintentional
  overdose. 2. Opioid "Pharmacokinetics" with
  antagonism. 
• 3. History/Physical, PMP and urine toxicology. 
• 4. Withdrawal medications in ICU/ambulatory.
• 5. What about naloxone (Narcan) ? 
• 6. Methadone for pain vs Methadone clinic?
• 7. Co-occurring and self-treating in a patients
  psychopathology.options?

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REMS

• Risk Evaluation and Mitigation Strategies
• Understand the epidemiology and problem.
• Monitor, PMP, Consent and Psych issues.
• Have exit plans and added training.

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• FDA has determined certain opioid products will
  be required to have REMS to help ensure that the
  benefits of the drugs continue to outweigh the
  risks of
• 1) use of certain opioid products in
  non-opioid-tolerant individuals
• 2) abuse and
• 3) overdose, both accidental and intentional.
• The REMS will include elements to help ensure
  that prescribers, dispensers, and patients are
  aware of and understand the risks. 

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• Pain and Symptom Management for Health Care
  Professionals
• Welcome to the portion of the Pain and Symptom
  Management website devoted to information for
  both Michigan health care providers and health
  policy professionals. This part of the website
  will provide health care professionals with state
  and national guidelines, Michigan legislation,
  educational links and various articles and
  publications related to pain and symptom
  management. Health Professionals are also likely
  to find this website's link to the Advisory
  Committee on Pain and Symptom Management of
  interest.
• State and National Guidelines Click here for
  state and national guidelines for pain and
  symptom management
• Palliative Care Click here for Information about
  chronic disease and cancer-related palliative
  care Links to Pain and Symptom Management
  Information Click here for Links to Pain and
  Symptom Management Information
• Pain Symptom Management State Legislation Click
  here for information about state legislation
  pertaining to pain and symptom management
• End of Life Care Click here for pain management
  during the final days of life
• Publications and Articles Click here for
  publications/articles about pain/symptom
  management

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Select the single best answer

• Overdose victims are only new users.
• Heroin opioid deaths always increase together.
• Fatal opioid poisonings doubled (1999-2006).
• Doctors directly supplied non-Rx use of pain
  relievers greater than 70 of the time.
• Hospitalization, detox and incarceration lower
  your risk of opioid overdose.
• All of the above.
• None of the above.

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Select the single best answer

• Overdose victims are only new users.
• Heroin opioid deaths always increase together.
• Fatal opioid poisonings doubled (1999-2006).
• Doctors directly supplied non-Rx use of pain
  relievers greater than 70 of the time.
• Hospitalization, detox and incarceration lower
  your risk of opioid overdose.
• All of the above.
• None of the above.

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CDC/NCHS Sept 2009 From 1999 to 2006 fatal
poisoning with opioid analgesics increased from
4,000 to 13,800
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Wayne Co. Morgue
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Source Where Pain Relievers Were Obtained for
Most Recent Nonmedical Use among Past Year Users
Aged 12 or Older (NSDUH 2006)
Source Where Respondent Obtained
Bought on Internet0.1
Source Where Friend/Relative Obtained
Drug Dealer/Stranger3.9
Other 14.9
More than One Doctor 1.6
More than One Doctor3.3
Free from Friend/Relative7.3
Free from Friend/Relative55.7
One Doctor 19.1
Bought/Took fromFriend/Relative4.9
OneDoctor 80.7
Bought/Took from Friend/Relative14.8
Drug Dealer/Stranger1.6
Other 12.2
Note Totals may not sum to 100 because of
rounding or because suppressed estimates are not
shown. 1 The Other category includes the sources
Wrote Fake Prescription, Stole from Doctors
Office/Clinic/Hospital/Pharmacy, and Some Other
Way.
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Poisoning Mortality- USA
Unintentional, Drug-Related
Suicide
Undetermined Intent
Source Paulozzi L, et al. Pharmacoepidemiol Drug
Saf. 2006 Sep15(9)618-27.
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Michigan Poison Control

• DeVoss Hosp and DMC confirm in MI approx. 1,000
  opioid OD deaths per year.
• Wayne Co. (Detroit) alone (pop 2 million)
• 602 opioid OD deaths 2006
• 493 opioid OD deaths 2007
• 530 opioid OD deaths 2008
• OD deaths ½ in Detroit and ½ in non-Detroit

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2006
Florida Medical Examiner
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Who overdoses?

• Often dependent long term users not in treatment
  with 5-10 years of experience
• 17 occur in new users.
• Sporer Ann Emerg Med 2006

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Major risk factors

• Opioid Use following a period of abstinence
• Incarceration
• Hospitalization
• Drug treatment/detox
• Mixing classes of drugs
• Primarily other CNS depressants
• Cocaine is involved in nearly 40 of NYC
  overdoses
• Sporer 2006, Can Acad Emerg Med 2006

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Death following incarceration

• Post incarceration is major risk factor for death
  from OD
• Study of deaths in first 2 weeks post
  incarceration among 30,237 released inmates
• 129 times greater likelihood of dying of OD vs.
  other WA state residents
• 60 involved opioids
• 74 involved cocaine and other stimulants
• Bingswanger NEJM 2007

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DEA (2005) 22 states Rx in crime
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Heroin overdoses droppingAllegheny County
Trends in Accidental Drug Overdose Deaths
(2000-2006) 2000-2006
Opioid
Heroin
Data is from Allegheny County Medical Examiners
Annual Reports and includes all overdose deaths
where these drugs were present at time of death,
not necessarily cause of death.
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Scripts Reported in 2003-2006 by MDCH on the MAPS

• 2003 12,498,338
• 2004 13,689,728
• 2005 14,355,989
• 2006 15,989,785
• 2008 17,311,431
• Hydro/APAP 5,116,486
• 30

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Schedule II MAPS methadone info

• 2003 72,172 scripts
• 2004 109,869 increase of 52
• 2005 131,524 increase of 20
• 2006 162,736 increase of 22
• Medicaid requires prior approval for Oxycontin
  and not for methadone there will be a transfer
  due to this formulary issue.

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Get MAPS report online and do a urine drug
screen. Record results in Text of the progress
note.
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Resources at the State of Michigan

• Department of Community Health
• Bureau of Health Professions
• www.michigan.gov/healthlicense
• Health Investigation Division
• mapsinfo_at_michigan.gov
• http//sso.state.mi.us/

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What is a good urine drug test?
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What is a good urine drug test?

• CLIA waivered
• Temperature and Specific Gravity
• 12 panel drug test
• 10 minute developing (POS)
• Closed system
• 6.95-7.95

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Only 8 of primary care use urine drug toxicology
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Call Poison Control Center

• Identify yourself
• Request a Toxicologist
• Report patient demographics/data
• Record orders in chart

1-800-222-1222
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Morphine
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Heroin is diacetylmorphine
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Physiology of overdose

• Overdose happens over course of 1-3 hours
  stereotypic needle in the arm death is only
  10-15
• Opioids depress the urge to breath and decrease
  response to carbon dioxide - leading to
  respiratory depression and death
• Sporer Ann Emergency Med 2007

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Overdoses cannot be cookbook

• Heroin
• Active metabolites
• 6-MAM (short t½)
• Morphine
• Half-life 3-4 hours
• Often w/ cocaine
• Narcan

• Methadone
• Inactive metabolites
• EDDP
• Half-life12-40 hours
• Often w/ benzos
• Narcan is not enough
• Often intubated
• You cant cheat time!

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Always make the patient naked.

• Look for fentanyl patches or residual glue.
• Examine tattoos and look for needle marks.
• Rectal exam especially if unconscious and arrest
  in the field also look for cut up fentanyl
  patches in the oral cavity (Chiclets).

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lungs _at_ autopsy gt1,400 grams
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Progression

• Treating the acute overdose state.
• ABCs
• Oxygen
• Narcan
• Fluid
• Blood pressure

• Treating the detoxed patient that results after
  the overdose.
• Anti-siezure meds
• Nausea
• Panic anxiety
• Pain (myalgia)
• Pysch meds/eval

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• Naloxone
• Pharmacokinetics

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Naloxone
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Naloxone (Narcan)

• Opioid antagonist which reverses opioid related
  sedation respiratory depression and may cause
  withdrawal.
• Displaces opioids from the receptors, then
  occupies the receptor for 30-90 minutes
• No psychoactive effects
• Over the counter in Italy
• Routinely used by EMS

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AGONIST
DECREASED
MAXIMAL
EFFECT
PARTIAL
AGONIST
EFFECT
Antagonist
LOG DOSE
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Adjuvants

• Adjuvants allow easier opioid withdrawal or give
  analgesia in place of low dose opioid.
• Gabapentin or Namenda or Amantadine
• Valproic Acid / Phenytoin/ Pregabalin
• Amitriptyline/hydroxazine or Benadryl
• Promethazine or Dextromethorphan
• Baclofen or Ranitidine or Clonidine
• Carbamazepine 200-1600mg per day.

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Treat and cover seizures in polypharmacy
withdrawal

• Carbamazepine suspension 100mg/5mL given oral
  or rectal (10mL to 80mL)
• Diastat (diazepam 2.5, 5mg rectal gel)
• Lorazepam 2-4mg I.V. push prn seizures
• Phenobarbital seizure/anxiety/insomnia

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Heroin Overdose in France
Source Carrieri PM, 2006, Clin Infect Dis, 43
S197-215, data from Emmanueli
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Select the single best answer

• Methadone treatment increased overdose risk.
• Methadone escalation is greater than morphine.
• Methadones metabolite is more toxic.
• Methadone overdose deaths are monotherapy greater
  than 74 of the time.
• Methadone has no federal or public guidelines or
  web page for methadone use.
• All of the above.
• None of the above.

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Select the single best answer

• Methadone treatment increased overdose risk.
• Methadone escalation is greater than morphine.
• Methadones metabolite is more toxic.
• Methadone overdose deaths are monotherapy greater
  than 74 of the time.
• Methadone has no federal or public guidelines or
  web page for methadone use.
• All of the above.
• None of the above.

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Do not use Methadone unless you are very
comfortable with it.

• Document reasons clearly for using methadone
• Hospice
• Allergies
• Formulary
• Diagnosis
• MMTs /MTPs

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Paid for with taxpayer dollars.

• Where do you get your copy?
• Internet
• Print
• DHHS publication No. 04-3904

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• Let us look at Methadone for pain clinics and
• Methadone for pain in primary care.

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FAQ

• Why do we use methadone?
• Is methadone dangerous?
• How do I learn methadone?

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• What is the Physician Clinical Support System -
  Methadone? (PCSS-M)
• The Physician Clinical Support System for
  Methadone (PCSS-M) is a free, nationwide program
  through which health care providers needing
  information and mentoring on methadone treatment
  for opioid addiction and/or pain can connect with
  experts in the field. PCSS-M MENTORS provide
  telephone, email and on-site support. They come
  from across the country and work in licensed
  opioid treatment programs, pain clinics, primary
  care, and other practice settings. The PCSS-M is
  coordinated by the American Society of Addiction
  Medicine (ASAM) in conjunction with other leading
  medical societies. PCSS-M offers a national
  network of trained health care provider mentors
  with expertise in the clinical pharmacology of
  methadone and clinical education. Mentors are
  supported by NATIONAL EXPERTS in the use of
  methadone and by a MEDICAL DIRECTOR, C0-MEDICAL
  DIRECTOR, and SENIOR ADVISOR.
• The PCSS-M MENTORS are members of medical
  specialty societies and provide mentoring support
  and educational services based on evidence-based
  practice guidelines. The efforts of PCSS-M are
  coordinated by a STEERING COMMITTEE composed of
  representatives from the Federal government and
  the leading pain and addiction medicine
  societies, along with primary care and
  psychiatric organizations that represent the
  target health care provider populations.
• PCSS-M provides educational services to any and
  all health care providers treating patients with
  methadone in an effort to increase the
  appropriate use and safety of this efficacious
  but clinically challenging medication.
• The PCSS-M is designed to offer support to
  clinicians treatment of pain and addiction on a
  number TOPICS including
• Patient assessment and selection
• Initiating and titrating methadone
• Conversion from other opioids
• Dosing and patient monitoring
• Interpreting methadone serum levels
• Drug-drug interactions
• Methadone and cardiac conduction
• Minimizing risk of diversion and overdose
• Management of co-occurring conditions
• This project is funded by a grant from The
  Department of Health and Human Services,
  Substance Abuse and Mental Health Services
  Administration (SAMHSA), Center for Substance
  Abuse Treatment (CSAT) grant1H79TIO20294-01. 

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• OPIOID TREATMENT PROGRAM
• Mentor Name Specialty Location
• Gavin Bart, MD OTP Minneapolis, MN Mark
  Jorrisch, MD OTP Louisville, KY Mark Kraus, MD,
  FASAM OTP Waterbury, CT Edwin Salsitz, MD OTP
  New York, NY Laurene Spencer, MD OTP
  Hillsborough, CA Trusandra Taylor, MD OTP
  Philadelphia, PA Alex Walley, MD, MSc OTP
  Boston, MA Charles Walton, MD OTP Highland, UT
  Susan Whitley, MD OTP New York City, NY George
  Woody, MD OTP Philadelphia, PA
• PAIN TREATMENT
• Mentor Name Specialty Location
• Howard Heit, MD, FACP, FASAM Pain Treatment
  Fairfax, VA
• Brian McCarroll, DO, MS Pain Treatment Clinton
  Township, MI
• Mary McMasters, MD Pain Treatment Fishersville,
  VA
• William Morrone, DO, MS, ASAM, ACOFP, DAAPM Pain
  Treatment Bay City, MI
• Randy Seewald, MD Pain Treatment New York City,
  NY
• William Yarborough, MD Pain Treatment Tulsa, OK
• PRIMARY CARE
• Mentor Name Specialty Location
• Jeff Baxter, MD Primary Care Worcester, MA
• John Brooklyn, MD Primary Care Jericho, VT
• Anthony Dekker, DO Primary Care Phoenix, AZ

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How do you get that web page?

• http//www.pcssmethadone.org/pcss/index.php
• A free nationwide program (PCSS-M) that
  healthcare providers needing information and
  mentoring can connect to methadone experts in
  addiction and pain management. A similar web
  resource exists for buprenorphine (PCSS-B).

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Pharmacology

• Efficacy greater than morphine
• Full Mu-opioid agonist
• Inhibits reuptake of 5HT and NE.
• NMDA antagonist resulting in additional analgesia

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Analgesia similar to morphine

• Once daily for opioid addiction (MMT only)
• Liquid used mostly for addiction and HOSPICE
• 15 mg morphine equal to 5 to 10 mg methadone
• 150 mg morphine equal to 30 mg methadone
• Suitable for pain when there is morphine allergy
• Slow onset helps avoid establishing reward
  behaviors that can occur with fast acting short
  duration opioids

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Less dose escalation with methadone?

• N40, advanced cancer
• methadone vs morphine
• Doses of both drugs were minimized and titrated
  to acceptable analgesia with minimal adverse
  effects.
• Pain control and side effects were similar
• Pill counts.
• Opioid escalation was significantly less with
  methadone
• More stable analgesia over time was seen in
  patients treated with methadone.
• Mercadante S et al. J Clin Oncol
  1998163656-3661.

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Methadone Pharmacokinetics

• Metabolized in liver NO active metabolites
  (EDDP).
• Elimination half life of about 22 hours but
  varies in each person.
• Duration 8-12 hours with repeated dosing.
• Minimal renal excretion primarily fecal excretion.

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Methadone Dosing

• Package insert advised dosage of 2.5 to 10mg
  every 3-4 hours as needed
• 40-50 mg/day can be deadly for new patient
• FDA black box warning
• 18 deaths - Kent county, 11 deaths - Bay County
  (2006)
• 2003 DAWN data from MEs in Detroit identified 64
  deaths from methadone
• Benzos found in 74 of deaths related to
  methadone
• Marked drowsiness (side effect) add
  methylphenidate
• Duration of analgesia about 8 hours (6 to 10
  hours)

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Hospice White Male end stage liver chirrosis,
type2 NIDDM, HCV, tibial ulcer LE DNP
PRE

• 2 Vicodin q 4-6 hours
• 800 mg IBU q 8
• Valium 5 q 8
• Percocet 5 q HS
• Restoril 30 q HS

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Hospice White Male end stage liver chirrosis,
type2 NIDDM, HCV, tibial ulcer LE DNP
POST

• 5mg methadone po q 8 to 12
• One Vicodin q 24 prn
• 250mg (bed time only) carisoprodol q HS
• 600mg gabapentin q 8
• 25mg nortriptyline q HS
• 10mg baclofen q 8

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Honest talk about addictions.
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Methadone and mortality

• Prospective study of opioid dependent patients
  applying for methadone treatment in Norway
• 3,789 subjects followed for up to 7 years
• Clausen Drug Alc Dep 2008

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Results
Pre-treatment In treatment Post-treatment
Total mortality Odds ratio 1 0.5 1.43
Total overdose Odds ratio 1 0.20 1.40
Percent of deaths due to overdose 79 27 61
Clausen 2008
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Send recovered patients to treatment
CBT/individual/group
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Maintenance therapy prevents overdose
Since the institution of buprenorphine and
methadone maintenance in 1996 in France heroin
overdose dropped 79
French population in 1999 60,000,000
Patients receiving buprenorphine (1998) N 55,000
Patients receiving methadone (1998) N 5,360
Auriacombe et al., 2001
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Selecting treatment modalities

• Consider
• Patient expectations of treatment
• Patient goals (detox vs maintence)
• Stages of change
• Current circumstances
• Available resources
• Past history of treatment outcome
• Evidence regarding safety, efficacy and
  effectiveness
• Need for pain management

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Outpatient and Inpatient

• Victory Clinical Services 989.752.7867
• Recovery Pathways, LLC 989.928.3566
• Michigan Behavioral Health Institute Dr.
  Douglas Foster 989.894.3000
• Detroit, Flint or Mt. Pleasant methadone clinic
• White Pine / HealthSource (inpatient)
• Bay Regional Medical Center (inpatient)

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End Game examples

• Opioid overdose w/ pain management should change
  to buprenorhine/naloxone or methadone clinic and
  therapy.
• Heroin overdose should go to methadone clinic for
  structure and therapy.
• Street opioid overdose should go to methadone
  clinic for structure and therapy.
• Opioid overdose with multiple outpatient failures
  go to methadone clinic.

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BIG TAKE HOME POINT

• Do not try to be a methadone clinic in your
  office.
• Dependence must be separated from pain.
• Keep methadone pain management patients and make
  your charts absolutely 100 unambiguous with
  supporting documentation with reassessment .

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Naltrexone Core
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Slide Acknowledgements

• Alice Bell
• Melinda Campopiano, MD
• Sharon Stancliff, MD

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Call any time.

• Director of Hospice and Palliative Care
• Hospice of Michigan - 989.790.7352.
• Assistant Director Family Medicine
• Synergy Medical Alliance - 989.583.6800.
• 24 hour Answering Service 989.891.8979
• Any question. Any medicine.
• william.morrone_at_sbcglobal.net