The Good, the Bad, and the Ugly - Dalhousie University...The Good, the Bad, and the Ugly John Fraser...
Transcript of The Good, the Bad, and the Ugly - Dalhousie University...The Good, the Bad, and the Ugly John Fraser...
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Opioids
The Good, the Bad, and the Ugly
John Fraser
November 22, 2018
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“Opioid Crisis”
1. Increase in overdoses and addiction in patients prescribed opioids for chronic pain
2. Increase in overdose deaths in patients with addiction due to high-potency illicit opioids
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•Opiate
•Opioid
•Narcotic
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Opiate
• Natural substance found in Papaver somniferum (opium poppy)
• Morphine
• Codeine
• Thebaine
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Opioid
• Reacts with opioid receptor in the brain
• Semi-synthetic
– Oxycodone (Percocet, Oxycontin)
– Hydromorphone (Dilaudid, Hydromorph contin)
– Heroin
• Synthetic
– Methadone
– Fentanyl
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Narcotic
• Psychoactive substance used for non-medical purposes, usually illegal
– Cocaine
– Crystal meth
– Heroin
– Prescription opioids
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Morphine
Codeine (Tylenol #3) 1/6
Oxycodone (Percocet, Oxycontin) 1.5
Hydromorphone (Dilaudid, Hydromorph contin) 5
Meperidine (Demerol ) 1/10
Methadone (Metadol) 10
Buprenorphine (Suboxone) 40
Fentanyl (Duragesic ) 80
Carfentanyl 8000
Heroin 5
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Opioids
• Opioid – from Greek “opos” meaning “juice”
• 4000 BC - Sumerians
• 3400 BC – Mesopotamia
• 800 AD – traders brought opium to India and China
• 1600 – opioid addiction first described
• 1806 – morphine isolated (Sertürner)– From “Morpheus” – Greek god of dreams
– First active drug purified from a plant sourcePecoraro et al, 2012, Subst Use Misuse
Alam et al. Can J Anaesth. 2016;63:61-8
Helal et al. Eur J Med Chem. 2017;141:632-47
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Opioids
• 1810 – addiction defined as a disease (Rush)
• 1874 heroin synthesized (C.R. Wright)
– From “heroisch” – heroic or strong
• 1897 – heroin marketed
– Cough suppressant
– Treatment for morphine addiction
• 1910 – heroin primary illicit drug in USA
• 1924 – heroin banned in USA
Pecoraro et al, 2012, Subst Use Misuse
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The GOOD
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Sydenham 1680
“Among the remedies which it has pleased Almighty God to give man to relieve his suffering, none is so universal and so efficacious as opium”
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Opioids for Pain
• Acute pain
• Cancer pain
• Chronic pain
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Chronic Pain in Canada
Region %
Atlantic 22
Quebec 16
Ontario 17
Prairie 20
Alberta 21
British Columbia 22
Canada 19
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Chronic Pain in Canada
Schopflocher et al. Pain Res Manage. 2010;16:445-50
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Chronic Pain in Canada
Schopflocher et al. Pain Res Manage. 2010;16:445-50
• 23% have pain more than 20 years
• 47% have pain more than 10 years
• 32% pain is severe
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Opioids for Chronic Pain
• Cochrane review
• 26 studies, n=4893
• Almost all studies less than 12 weeks
• Weak evidence for long term pain relief
• 33.2% drop out
Noble et al. Cochrane Database Syst Rev. 2010
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Opioids for Chronic Pain
• Benefits of opioids roughly equivalent to other pain medications
– Reduction in pain in 11%
– Improvement in function in 10%
• But complications are more common
• Reserved for patients with severe pain that does not respond to other treatments
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Physical Therapies
• Physiotherapy
• Chiropractic
• Massage
• Yoga
• Tai Chi
• Acupuncture
• Exercise
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Psychological Therapies
• Mindfulness
• Relaxation
• Meditation
• Pain self management group
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Drug Therapies
• Anti-inflammatory (ibuprofen, naproxen)
• Acetaminophen
• TCA (amitriptyline, nortriptyline)
• Gabapentin, Pregabalin
• Duloxetine
• Cannabinoids (Nabilone)
• Injections
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Opioid Dosing
Past
• Increase the dose until pain is adequately reduced
Present
• Maximum dose of 90 mg morphine for most patients
• Discontinued if there is no significant pain reduction and functional improvement
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Complications of Opioid Therapy
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The BAD
• Falls
• Sedation
• Mental functioning
• Sleep apnea
• Hyperalgesia
• Depression
• Addiction
• Overdose
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The BAD
• Falls twice as many fractures
• Sedation
• Mental functioning poor memory, fuzzy thinking
• Sleep apnea 8 times more common
• Hyperalgesia
• Depression 3 times more common
• Addiction
• Overdose
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Addiction Risk in Chronic Pain
• 5.5% overall
• 9% with active addiction
• 8% with active mental illness
• Less than 0.2% with no history of addiction
– About one in 600 patients
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Addiction Risk in Chronic Pain
• Systematic review
• 17 studies
• Available evidence suggests that opioid analgesics for chronic pain conditions are not associated with a major risk for developing addiction
Minozzi et al, 2013, Addiction
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Addiction Risk in Chronic Pain
• Personal history of addiction
• Family history of addiction
• History of mental illness
• History of childhood trauma
• Age less than 45
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Opioid Overdose
Morphine equivalent Overdose death
50 to 200 mg 2 times the risk
over 200 mg 3 times the risk
Gomes et al, 2011, Arch Int Med
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USA non-medical use of opioids2001 to 2009
Imtiaz et al, 2014, Subst Abuse Treat Prev Policy
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Prescription Opioids in Canada
• Second highest globally
• 23% increase in doses over 200 mg OME from 2006 to 2011
• Proportion of overdose deaths in Ontario caused by prescription opioids rose from 34% in 2002 to 72% in 2012
• 5% population prescribed opioids use them for unintended reasons
Murphy et al. Pain Physician. 2015;18:E605-E614
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“Opioid Crisis” #1
How did this happen?
• 1970’s and 80’s
– Pain is undertreated
– Opioid therapy is safe and effective
– Increase the dose as high as needed
• Insufficient education of chronic pain management in medical school and residency
• Prescriber response to patient's suffering
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“Opioid Crisis” #1
• Too many patients prescribed opioids
• Opioids prescribed to patients with higher risk
• Opioids prescribed at doses much higher than currently recommended
Resulting in increasing rates of:
• Opioid addiction
• Opioid overdose
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“Opioid Crisis” #1
What is the response?
• National Chronic Pain treatment guidelines (2010, 2017)
• Education– Practicing physicians
– Medical school
– Residency
– Public
• Safer opioid formulations
• Prescription Monitoring Programs
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The UGLY
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Opioid Addictionmillion
Asia 8.1 0.20%
Australasia 0.1 0.46%
Europe 2.1 0.30%
Latin America 1.4 0.25%
North America 1.0 0.30%
North Africa 1.4 0.29%
Sub-Saharan Africa 1.2 0.16%
GLOBAL 15.5 0.22%
Degenhardt et al. Addiction. 2014;109:1320-33
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“Opioid Crisis” #2
Heroin, fentanyl, carfentanyl–Very high potency
–Manufactured illicitly
• No pharmaceutical quality control
–Concentration unknown from dose to dose
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“Opioid Crisis” #2
This has lead to a very significant increase in overdose deaths in people with opioid addiciton
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Addiction
Chronic brain disease
Many factors influencing its development and manifestations
• Genetic
• Environmental
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Addiction
Like other chronic diseases, it can be
• Progressive
• Relapsing
• Fatal
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Addiction
• Addiction is not a choice
• Starting drug use is a choice
• Stopping drug use is a choice
and
• Starting treatment is a choice
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Drugs don’t cause addiction
Addiction develops
in the “at risk” population
in the right setting
with the right drug
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Reward Circuit
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Frontal cortex
• Problem solving
• Spontaneity
• Initiation
• Judgement
• Impulse control
• Social behaviour
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Addiction – The four C’s
•Craving
•Compulsive use
• impaired Control
•Continued use despite harm
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Continued Use Despite Harm
• Physical
• Psychological
• Social
• Spiritual
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Physical Effects
• HIV 15%
• Hepatitis C 80% (150 times)
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Psychological Effects
60 % with mental illness
• Depression
• Anxiety
• Psychosis
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Social Effects
• Relationships → family breakup
→ loss of friends
• School → drop out
• Work → unemployment
→ poverty
→ income assistance
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Social Effects
• Social life → isolation
→ marginalization
• Housing → substandard
→ homelessness
• Law → DWI
→ crime
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Spiritual Effects
• Loss of meaning and purpose
• Loss of relationship with humanity
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Opioid Addiction - Halifax
• Age 35 (17 to 72)
• Homeless 27%
• Social assistance 81%
• Injecting 80%
• Hydromorphone (Dilaudid®)
– Acute pain 50 mg
– Chronic pain 90 mg
– Addiction 1160 mg (20 times usual dose)
• Some heroin and fentanyl
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Addiction Treatment
• Stages of change
• Motivational interviewing
• Harm reduction
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Stages of Change
• Pre-contemplation denial
• Contemplation not ready
• Preparation ambivalent
• Action
• Maintenance relapse
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Action
• Patient actively engages in change
• Requires greatest commitment and energy• Repairing broken relationships
• Learning new coping strategies
• Dealing with mental illness (± trauma)
• Filling time
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Motivational Interviewing
• Help patient move through stages of change and maintain action
• Change comes from within
• The patient should come up with the arguments for change
(not the worker)
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Motivational Interviewing
Change is motivated by a discrepancy between behavior and important goals and values.
“So on the one hand, you tell me that you really want to have a good relationship with your spouse. That is very important to you. But on the other hand, your drug use seems be causing significant problems in your relationship. That’s a pretty difficult situation.”
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Harm Reduction
• Respect the decisions people make about their lives
• Provide assistance to maximize their health and reduce harm
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Harm Reduction
• Collaboration
• Pragmatism
• Non-judgmental attitude
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Non-Judgemental Attitude
• Respect
• Acceptance
• Compassion
• Honesty
• Transparency
• Trust
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Harm Reduction
• Self treatment, “cold turkey”
• Community based outreach programs
• Supervised consumption sites
• Needle exchange programs
• Abstinence based programs– Addiction services (detox, group, counselling)
– Residential treatment programs
– 12 step programs (AA, NA)
• Medications
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Harm Reduction Strategies
Spectrum of interventions
abstinence methadone needle supervised naloxone ?? exchange consumption
site
Opioid Use Disorder
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Harm Reduction • 34 year old woman
• 4 year history of intravenous heroin addiction
• Not interested in stopping
Intervention
• Motivational interviewing to become ready for treatment
• Harm reduction– Naloxone kit
– Needle exchange
– Safe injecting behaviours
– HIV, hepatitis C testing
– Return appointment
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Treatment of Opioid Addiction
Abstinence-based treatment
–Detox
–Counselling
–NA
–Residential centres
• Most patients relapse
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Treatment of Opioid Addiction
Opioid Agonist Therapy (OAT)• Methadone and buprenorphine (Suboxone®)
• 70% less opioid use
• 90% less overdose deaths
• 50% less HIV transmission
• Significantly less crime
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Methadone
• 1937: synthesized in Germany for anlagesia on the front line (never used)
• 1959: first used for addiction by Halliday in Vancouver
• Standard of care
• Once daily oral solution, mixed in Tang®
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Buprenorphine
• 1969: first synthesized in the lab
• 1982: first used for opioid addiction in Britain
• Once daily sublingual tablet mixed with naloxone
– Naloxone not absorbed, but if injected causes severe withdrawal
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Why Does OAT Work
• Once daily dose
• Effect lasts 24 hours
• Eliminates withdrawal and cravings
• Little euphoric effect
• Blocks euphoric effects of other opioids
• No sedation or cognitive changes
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Choice
Methadone Buprenorphine
More patients stayin treatment
Lower risk of overdose
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Process of OAT
• Counselling– Peer– Addiction counsellor– Groups
• Advocacy– Housing– Legal issues– Employment
• Other chronic diseases– HIV– Hepatitis C– Mental illness– Chronic pain
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Direction 180
admission 6 months
Number using 100% 33%
UDS opioids 88% 15%
Amount used 1160 mg 96 mg
Injections/week 51 <1
Homeless 27% 15%
Sex work 18% 2%
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Take Home Doses
• Initially daily witnessed ingestion
• Goal of treatment to normalize life
• Evidence of stability
– No drug use (urine tests)
– Stable, safe housing (safe storage)
– No active mental illness
• Gradual increase from one carry a week to 6
• Taken away at the first sign of instability
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Coming off Medication
• Neither planned nor necessary
– Chronic disease
• Predictors of success
– Right reason
– Right time
• 1 year stable
– Right way
• 70% relapse
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Summary
• Chronic pain is common (22% in Canada)
• Opioid therapy has limited long term effectiveness but is associated with significant complications
• Opioid therapy is reserved for severe pain when all other treatments have failed
• Opioid therapy should not be prescribed to patients with higher risk
• Opioid dose should be limited to 90 mg morphine for most patients
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Summary
• Opioid addiction is a brain disease with severe negative consequences
• Harm reduction is a spectrum of strategies to reduce the harmful effects of drug use
• Opioid agonist therapy (methadone or buprenorphine) is the treatment of choice for opioid addiction
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Summary
“Opioid Crisis” #1
• Increase in overdoses and addiction in patients prescribed opioids for chronic pain
• Cause
– Over prescribing of opioids in patients with chronic pain
• Strategies
– National opioid prescribing guidelines
– Education
– Prescription monitoring programs
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Summary
“Opioid Crisis” #2
• Increase in overdose deaths in patients with addiction due to high-potency illicit opioids
• Cause
– Very potent non-pharmaceutical opioids with unpredictable concentrations (fentanyl, carfnetanyl)
• Strategies: harm reduction
– Naloxone
– Supervised injection sites
– Opioid agonist therapy
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Questions