Transcript this Presentation - Alcohol Medical Scholars Program

Buprenorphine
Daryl Shorter, MD
Michael E. DeBakey VA Medical Center
Menninger Department of Psychiatry and Behavioral Science
Baylor College of Medicine
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22.5 million Americans (8.7%) current
users of illicit substances
2.33 million persons with
Opioid Use Disorder
426,000 persons
with heroin abuse
or dependence
1.8 million persons
with pain reliever
abuse or dependence
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This Lecture Reviews
1. Definitions
2. Course of Opioid Use Disorder (OUD)
3. Treatment of OUD
4. Role of buprenorphine in long-term Rx
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Opioid Brain Effects
• Decrease pain (via μ-opioid receptor)
• Suppress cough
• Increase constipation
• Cause euphoria (μ-opioid receptor)
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Opioids
• Heroin – no medical use
• Morphine – Rx for pain
• All prescription pain meds (unless antiinflammatory)
– Oxycodone (Oxycontin)
– Hydrocodone (Vicodin, Lorcet, Lortab)
– Methadone (Dolophine)
– Buprenorphine (Subutex)
– Tramadol (Ultram)
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DSM-5 Opioid Use Disorder
• Tolerance
• Hazardous use
• Withdrawal
• Physical/psychological
problems from use
• Attempts to cut down
• Much time spent using
• Social/interpersonal
problems from use
• Use larger amounts
• Activities given up
• Neglecting roles
• Craving
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Opioid Withdrawal
• Dysphoric (sad) mood
• Nausea/vomiting
• Muscle aches
• Diarrhea
• Lacrimation (tearing) or
rhinorrhea (runny nose)
• Yawning
• Pupillary dilation,
piloerection (goose
flesh), or sweating
• Fever
• Insomnia
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Opioid Overdose
• 2nd highest cause of accidental death
• 17,000 opioid overdose deaths (2010)
• Cause of death = respiratory depression
• ~7 non-fatal OD for every fatal OD
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Opioid Overdose
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↓ consciousness
↓ respirations (< 12/min)
Miotic (pinpoint) pupils
Evidence of opioid use (needle track marks)
• Management: Opioid antagonist, naloxone
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This Lecture Reviews
1. Definitions
2. Course of Opioid Use Disorder (OUD)
3. Treatment of OUD
4. Role of buprenorphine in long-term Rx
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Course of OUD
OUD
Nonmedical Use
Prescription Rx
Exposure to Pain or street drugs
Relievers or seek
opioid high
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Health Risks OUD
• Accidental injury
– 2-5x ↑ risk of falls & fractures
– ~3x ↑ risk of mortality from vehicular accidents
• 4x ↑ risk of overall mortality
• ↑ risk of HIV & Hepatitis C
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Social Consequences
• ↑ Criminal behavior & crime-related costs
• Education
–  GPA; ↑ truancy
• Violence
• Loss job and family
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Relapse
• 6 months after treatment ~50% abstinent
• 10 years after treatment ~25% abstinent
There is a need for effective treatment.
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This Lecture Reviews
1. Definitions
2. Course of Opioid Use Disorder (OUD)
3. Treatment of OUD
4. Role of buprenorphine in long-term Rx
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Goals of OUD Treatment
1. ↓ withdrawal symptoms
2. ↓ craving
3. Prevent relapse
4. ↑ physiologic state/ improve functioning
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Case - Jimmy
• 32y male, presents to ER
• Reports 12+ year hx of opioid misuse
• Last use of heroin ~12 hours ago
• Anxious, sweating, nauseous, pupils dilated
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Clinical Opioid Withdrawal Scale
• 11-item COWS assessment:
pulse, sweating, pupil size, yawning, anxiety
• Scores characterize withdrawal:
– 5-12 = mild
– 13-24 = moderate
– 25-36 = moderately severe
– ≥36 = severe
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Withdrawal Management
• Use clonidine (Catapres) to  withdrawal
– α2-adrenergic agonist to  adrenalin
– Treats hypertension
• Rx other symptom as needed
– Loperamide (Imodium) for diarrhea
– Ibuprofen (Advil) for bone/muscle pain
– Medications for insomnia
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Withdrawal Management (2)
• Symptom-triggered clonidine Rx
– For COWS > 8, give 0.1-0.2mg clonidine
– On day 1, target dose of 0.3-0.6mg
– May  to 0.6-1.2mg/day, as necessary
– Once stabilized, reduce daily dose by 50% per day
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•Clonidine
Opioid
Withdrawal •Agonist
Long term •Antagonist
Rx of OUD •Agonist
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Withdrawal Management (3)
Use opioid agonist to  symptoms
• Methadone
– Up to 30mg/day
–  10-20% every 1-2 days over 2-3 weeks
– Better than α2-adrenergic agonist based Rx
• Buprenorphine
– Up to 8mg/day
– ↓ by 2mg every 1-2 days over 7-10 days
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•Clonidine
Opioid
Withdrawal •Agonist
Long term •Antagonist
Rx of OUD •Agonist
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Long-term Rx of OUD
• Opioid Antagonist Therapy
– Intramuscular naltrexone (Trexan)
• Administer every 30 days
• Prevents opioid high
• Low compliance
– No other FDA-approved medications
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Long-term Rx of OUD (2)
• Methadone maintenance treatment (MMT)
– Taken daily by mouth
– Obtained through federally-regulated program
– Optimal dose varies (target = 80mg/day)
-- Must ↑ dose slowly to avoid OD
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MMT Drawbacks
• Overdose common in early treatment
• Cannot be prescribed from general practice
• Strict government control and paperwork
• Stigma of daily clinic attendance
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This Lecture Reviews
1. Definitions
2. Course of Opioid Use Disorder (OUD)
3. Treatment of OUD
4. Role of buprenorphine in long-term Rx
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Office-Based Buprenorphine
• Taken daily, sublingually
• Rx in offices of physicians with special training
• Individual dose varies (target = 16-24mg/day)
• Daily visits not necessary
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Buprenorphine Pharmacology
• Partial agonist at μ-opioid receptor
• Slow dissociation from receptor
• Half-life = 24-36 hrs
• Metabolizes quickly, if give orally
• So Rx is sublingual or buccal
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Buprenorphine Pharmacology (2)
• Clinical impact
– Less subjective euphoria than methadone
– Long-lasting clinical action
– Partially blocks intoxication
– Reduced overdose risk
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Formulations
• Buprenorphine alone (Subutex)
• Buprenorphine + naloxone (Suboxone)
– Naloxone = antagonist
–  risk of diversion and IV misuse
– Combined in 4 mg bup:1 mg naloxone
• Combo in sublingual or buccal film
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More Buprenorphine Info
• Side effects
– Neuro: Sedation, dizziness, headache
– GI: Constipation, nausea/vomiting
– Respiratory depression
• Availability and cost
– Prescribed by MDs with special training
– Reimbursed by Medicaid, health insurances
--But costs more than methadone
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Buprenorphine Treatment
• Initiation
– Goal: avoid precipitated withdrawal & OD
– Patient stops opioid misuse 12-36 hrs prior
– Patient demonstrates early withdrawal
• COWS rating > 8
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Buprenorphine Induction
• Induction phase (days 1-7)
– Day 1
• First dose = 4mg
• Assess for adverse effects
• Repeat 4mg dose if withdrawal symptoms
persist
• Maximum dose day 1 = 8 mg
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Buprenorphine Induction (2)
• Days 2-7
–  dose until withdrawal symptoms  (w/in 2 hrs)
– Day 2 dose: often  to 16mg
–  dose by Day 7 (usual to 8 – 24mg/day)
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Buprenorphine Stabilization
• Weeks 2-8
– Dose adjustment continues (up to 32mg/day)
– Characterized by
•   opioid craving
• No withdrawal symptoms
•  or absent opioid misuse
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Buprenorphine Maintenance
• Months 3-12
–Optimal dose reached
–Relapse prevention
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Buprenorphine Effectiveness
Buprenorphine (16mg/day)
Better than placebo and naltrexone
↑Treatment retention
 Opioid positive urines
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Buprenorphine v. Methadone
• Both improve outcomes
• Methadone → greater patient retention
• Buprenorphine benefits
Office-based Rx
Safer during induction
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Conclusions
• OUD is common and dangerous
• Buprenorphine is
A partial μ-opioid receptor agonist
Is safer
Is effective for office-based Rx
• Combined with naloxone → ↓ misuse
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