Opioid dependence and buprenorphine treatment David Roll, MD Revere Family Health, Cambridge Health Alliance Instructor in Medicine, Harvard Medical School Joji Suzuki MD Medical Director of Addictions Director of Addictions Education Department of Psychiatry, Brigham and Women s Hospital Instructor in Psychiatry, Harvard Medical School PCIM October 22, 2010
Pre-1995 Drug of Choice Heroin Age >30 Drug Source Use Patter Medical problems Legal problems Education Dealer IV Hepatitis C; HIV Common High school or less
Mechanism of action Mu opioid agonist But also antagonistic effects? 20-40x more potent than morphine Metabolism Hepatic (3A4, 2C8) Active metabolite: Norbuprenorphine Agonist at mu-receptor Protein binding Highly protein bound (>95%) Half-life Half life 20-70 hours Mean 37 hours Side effects Sweating Headache Nausea/vomiting Sedation
100 Treatment retention comparable to methadone 90 80 Methadone Buprenorphine 70 60 50 40 1 2 4 6 8 10 12 14 16 Strain 1994
70 Percent positive urine tests 65 60 55 Methadone Buprenorphine 50 45 40 35 30 Detoxification 2 4 6 8 10 12 14 16 18 20 22 24 26 Strain 1994
100 Treatment retention buprenorphine vs placebo, with intensive psychosocial support 90 80 70 60 50 40 Buprenorphine Placebo 30 20 10 0 4/20 subjects dead in placebo group by end of the study 0 50 100 150 200 250 300 350 Kakko 2003
In 2010 in the US, 23.1 million (or 9.1%) persons aged 12 or older needed treatment for an illicit drug or alcohol use problem SAMHHSA, 2011
Of the 23.1 million, 90% did not receive any treatment at a specialty treatment facility in 2010* *Treatment in inpaitient hospital, drug or alcohol rehabilitation facilities (in or outpatient), or mental health centers. Excludes ED, private doctor s office, self-help group, prison, jail, or hospital outpatient. SAMHHSA, 2011
Reasons for not receiving specialty treatment: 40.2% did not feel ready to stop 32.9% had no insurance and could not afford treatment 11.5% worried about the effects on job 11.3% worried about stigma from neighbors/community 9.3% did not know where to go SAMHSA, 2011
Overdoses involving opioids are among the leading causes of death among young adults 1. Unintentional injuries (53% overdose) 2. Cancer 3. Heart Disease Massachusetts death statistics 2008 Age Specific Rate per 100,000 800 700 600 500 400 300 200 100 0 Opioid Related Emergency Department Visits Ages 15-64, 2003-2005 203 450 578 532 731 360 Opioid Related Emergency Department Visits 266 Cambridge Chelsea Everett Malden Revere Somerville Massachusetts
2500 Trends in the non-medical use of psychotherapeutic medications (in thousands of new users) 2000 1500 Stimulants 1000 Sedatives/Tranquilizers Pain Relievers 500 0 1965 1970 1975 1980 1985 1990 1995 2000 SAMHSA, 2003
Pain relievers and marijuana most common drugs for new initiates (age 12 and older) Series 1 PCP Heroin Sedatives LSD Stimulants Cocaine Inhalants Ecstasy Tranquiliers Pain Relievers Marijuana 0 0.5 1 1.5 2 2.5 3 Thousands of new users SAMHSA, 2007
800 Morphine Milligram Equivalent (MME) per person in the US 700 600 500 400 300 200 100 0 1997 2007 DEA ARCOS system 2007
Source of misused prescription opioids Multiple doctors 19% One doctor 1% Drug dealer Internet 4% 0% Free from friend or family 56% Other 5% Bought or stolen from friend or family 15% SAMHSA, 2003
Initial source if bought/taken/given by family or friend Bought / taken from family or friend 5% Free from family / friend 7% More than one doctor 3% Drug dealer 2% Other 2% One doctor 81% SAMHSA, 2003
50000 45000 40000 35000 30000 25000 20000 Drug-induced deaths are dramatically increasing 15000 10000 5000 0 MVA Suicide Firearm injuries Homicide Drug-induced deaths 1999 2000 2001 2002 2003 2004 2005 2006 2007
Prescription opioids largest contributor to the increase in drug-induced deaths 14000 12000 10000 8000 Heroin Cocaine Prescription opioids 6000 4000 2000 0 1999 2000 2001 2002 2003 2004 2005 2006 2007
Pre-1995 Post-1995 Drug of Choice Heroin Prescription pain relievers Age Older Younger Drug Source Dealer Free from friends Use Pattern IV PO, snorting Medical problems Hepatitis C; HIV Pain Legal problems Common Uncommon Education High school or less College
Opioid prescribing Avoidance (pre 1990s) Fear of prescribing opioids even for dying patients After Nancy Wiedemer, Philadelphia VA Balance/Risk stratification Opioids as one part of treatment plan Increased use (1990s) Pain as 5 th vital sign Widespread use of opioids
State regulations and programs Licensing Requirements PMPs Opioid prescribing FDA REMS Insurers Dose and time limits PAs Physician Groups PROP petition
Who is a good candidate for buprenorphine prescribed by a primary care physician? Meets criteria for opioid dependence No unstable psychiatric issues Is agreeable to counseling / psychotherapy
Patient evaluation Opioid dependence ( Addiction ) T: Tolerance W: Withdrawal A: Amount C: Cut K: Use despite Knowledge of harm S: Spend a lot of time obtaining/using/recovering S: Social obligations are given up due to drug use
Patient evaluation Opioid withdrawal Anxiety Nausea/vomiting Mydriasis Restlessness Muscle aches Abd cramps Hot/cold flashes Yawning Rhinorrhea Pierceton Lacrimation Tremors
Primary Care Treatment Opioid Treatment Program Age Older Younger Reliability Higher Lower Motivation Higher Lower Social needs Lower Higher Psychiatric Less More comorbidity Pain Less More Level of function Higher Lower Knowledge More Less
Two key points about buprenrphine pharmacology
1) Buprenorphine BLOCKS other agonists: HIGH affinity and SLOW dissociation Mu Receptor Buprenorphine
2) Buprenorphine is a partial agonist 100 90 80 70 60 50 Full Agonist Antagonist Partial Agonist 40 30 20 10 0 No drug Low dose High dose
High affinity + partial agonism = potential for. Precipitated withdrawal
Buprenorphine will DISPLACE other agonists from receptor due to its high affinity Mu Receptor Full agonist
Precipitated withdrawal Administering buprenorphine while full agonists are present leads to ANTAGONIST effects
Precipitated withdrawal Administering buprenorphine while full agonists are NOT present leads to AGONIST effects
Precipitated withdrawal (with naloxone)
Formulation Brand Name Dosages Sublingual Suboxone: Buprenorphine + Naloxone Subutex: Buprenorphine Only 8/2 or 2/0.5mg 8 or 2mg Parenteral Buprenex 300mcg/ml The sublingual formulations are the Transdermal Butrans 5, 10, 20mcg/hr only ones approved for the treatment of opioid dependence Implant Probuphine Still in research
Treatment goals are straightforward 1) Eliminate withdrawal 2) Reduction in cravings 3) Reduction in illicit opioid use
Induction 1) Stop ALL opioid use for at least 8-10 hrs (longer if long-acting opioids) 2) Pick up induction prescription at pharmacy before coming in 3) Confirmation of mild withdrawal 4) Administer buprenorphine 4mg SL in office 5) Return to clinic 2 hrs later, and take additional 4mg dose 6) Take up to 12-16mg SL daily during first week 7) Remain in phone contact, return to clinic 1 wk later
Home induction Problems with standard inductions - time consuming for patient and provider - withdrawal symptoms in waiting room Home induction kit Home induction offered by 42% of Massachusetts prescribers (Walley 2008, Cunningham 2010)
Maintenance 1) Care Manager: 1) Available: Weekly office visits initially, and extend to monthly visits 2) Not available: Group visits?? 2) Should be seen by PCP q3-6 months 3) Regular counseling visits 4) Regular urine toxicology
Models of care Primary Care Group visits Private Practice: Psychiatry Nurse Care Manager Intensive Outpatient Opioid Treatment Program
Social outcomes improved in a primary care group visit program 90 80 70 60 50 40 % Before 30 % After 20 10 0 Employed Recovery Groups Housing Problems Legal Problems
Group Visits Benefits For Patients Increased access Increased face time with providers Peer support and encouragement For Providers Efficient Allows participation of addictions nurse Integrated treatment at primary care site
Maintenance treatment is more successful than detoxification Chronic disease model Relapses should be anticipated learning opportunities Other treatment counseling, 12-step programs Patient-centered tapering
Patient responses Groups keep my focus on the fact that I am not alone. I like having to answer to someone about my actions. Have pretty much controlled my sugar. I have weekend visitation with my son. I work as an assistant manager full time. I function very well without drugs.
Special populations that may not be appropriate for primary care clinicians without support Significant co-morbid chronic or acute pain Unclear if addiction or pain Pregnant Significant addiction or psychiatric co-morbidities
Co-occurring psychiatric disorders are common in patients with opioid dependence Depression Anxiety Personality disorders PTSD ADHD
Management of co-occurring psychiatric disorders and symptoms Differentiate substance-induced from independent psychiatric disorders Use standard first-line treatments Avoid medications with abuse potential
Chronic pain and addiction A common issue, but challenging to manage Very little in the literature to guide treatment Buprenorphine MAY be a full agonist for analgesia Use of full agonists as adjuncts to buprenorphine if needed Butrans NOT an option if pt has addiction
Obtaining the waiver Completion of an 8-hour course (or equivalent) is required a) On-line course b) National conferences c) PCSS-B listings d) Half-and-half course (4 hours self-study + 4 hours in-person)
www.pcssb.org www.asam.org www.aaap.org