Opioids

The Good, the Bad, and the Ugly

John Fraser

November 22, 2018

“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

•Opiate

•Opioid

•Narcotic

Opiate

• Natural substance found in Papaver somniferum (opium poppy)

• Morphine

• Codeine

• Thebaine

Opioid

• Reacts with opioid receptor in the brain

• Semi-synthetic

– Oxycodone (Percocet, Oxycontin)

– Hydromorphone (Dilaudid, Hydromorph contin)

– Heroin

• Synthetic

– Methadone

– Fentanyl

Narcotic

• Psychoactive substance used for non-medical purposes, usually illegal

– Cocaine

– Crystal meth

– Heroin

– Prescription opioids

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

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

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

The GOOD

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”

Opioids for Pain

• Acute pain

• Cancer pain

• Chronic pain

Chronic Pain in Canada

Region %

Atlantic 22

Quebec 16

Ontario 17

Prairie 20

Alberta 21

British Columbia 22

Canada 19

Chronic Pain in Canada

Schopflocher et al. Pain Res Manage. 2010;16:445-50

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

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

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

Physical Therapies

• Physiotherapy

• Chiropractic

• Massage

• Yoga

• Tai Chi

• Acupuncture

• Exercise

Psychological Therapies

• Mindfulness

• Relaxation

• Meditation

• Pain self management group

Drug Therapies

• Anti-inflammatory (ibuprofen, naproxen)

• Acetaminophen

• TCA (amitriptyline, nortriptyline)

• Gabapentin, Pregabalin

• Duloxetine

• Cannabinoids (Nabilone)

• Injections

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

Complications of Opioid Therapy

The BAD

• Falls

• Sedation

• Mental functioning

• Sleep apnea

• Hyperalgesia

• Depression

• Addiction

• Overdose

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

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

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

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

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

USA non-medical use of opioids2001 to 2009

Imtiaz et al, 2014, Subst Abuse Treat Prev Policy

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

“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

“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

“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

The UGLY

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

“Opioid Crisis” #2

Heroin, fentanyl, carfentanyl–Very high potency

–Manufactured illicitly

• No pharmaceutical quality control

–Concentration unknown from dose to dose

“Opioid Crisis” #2

This has lead to a very significant increase in overdose deaths in people with opioid addiciton

Addiction

Chronic brain disease

Many factors influencing its development and manifestations

• Genetic

• Environmental

Addiction

Like other chronic diseases, it can be

• Progressive

• Relapsing

• Fatal

Addiction

• Addiction is not a choice

• Starting drug use is a choice

• Stopping drug use is a choice

and

• Starting treatment is a choice

Drugs don’t cause addiction

Addiction develops

in the “at risk” population

in the right setting

with the right drug

Reward Circuit

Frontal cortex

• Problem solving

• Spontaneity

• Initiation

• Judgement

• Impulse control

• Social behaviour

Addiction – The four C’s

•Craving

•Compulsive use

• impaired Control

•Continued use despite harm

Continued Use Despite Harm

• Physical

• Psychological

• Social

• Spiritual

Physical Effects

• HIV 15%

• Hepatitis C 80% (150 times)

Psychological Effects

60 % with mental illness

• Depression

• Anxiety

• Psychosis

Social Effects

• Relationships → family breakup

→ loss of friends

• School → drop out

• Work → unemployment

→ poverty

→ income assistance

Social Effects

• Social life → isolation

→ marginalization

• Housing → substandard

→ homelessness

• Law → DWI

→ crime

Spiritual Effects

• Loss of meaning and purpose

• Loss of relationship with humanity

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

Addiction Treatment

• Stages of change

• Motivational interviewing

• Harm reduction

Stages of Change

• Pre-contemplation denial

• Contemplation not ready

• Preparation ambivalent

• Action

• Maintenance relapse

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

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)

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.”

Harm Reduction

• Respect the decisions people make about their lives

• Provide assistance to maximize their health and reduce harm

Harm Reduction

• Collaboration

• Pragmatism

• Non-judgmental attitude

Non-Judgemental Attitude

• Respect

• Acceptance

• Compassion

• Honesty

• Transparency

• Trust

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

Harm Reduction Strategies

Spectrum of interventions

abstinence methadone needle supervised naloxone ?? exchange consumption

site

Opioid Use Disorder

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

Treatment of Opioid Addiction

Abstinence-based treatment

–Detox

–Counselling

–NA

–Residential centres

• Most patients relapse

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

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®

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

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

Choice

Methadone Buprenorphine

More patients stayin treatment

Lower risk of overdose

Process of OAT

• Counselling– Peer– Addiction counsellor– Groups

• Advocacy– Housing– Legal issues– Employment

• Other chronic diseases– HIV– Hepatitis C– Mental illness– Chronic pain

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%

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

Coming off Medication

• Neither planned nor necessary

– Chronic disease

• Predictors of success

– Right reason

– Right time

• 1 year stable

– Right way

• 70% relapse

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

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

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

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

Questions