Opioids for Chronic Pain Where is the Science for the

Clinician David Borsook MD PhD

Professor HMS

1 MGH Center for Law Brain and Behavior

2 MGH Center for Law Brain and Behavior

Relative Status (Addiction and Pain) No Good Treatment for Chronic Pain

3 MGH Center for Law Brain and Behavior

Rela

tive

Stat

es

Drug War FAIL Drugs Now Kill More People Than Car Accidents httpthefreethoughtprojectcomopiates-killing-people-car-accidents

4 MGH Center for Law Brain and Behavior

Addi

ctio

n Pr

oble

m

MGH Center for Law Brain and Behavior 5

Pain

Pro

blem

25 Mill with severe pain 100 million with chronic pain 2 Mill on opioid addicts

6 MGH Center for Law Brain and Behavior

Rela

tive

Stat

es

Chronic pain costs US up to $635 billion Prescription Opioid Epidemic $78 billion

Depression chronic pain and suicide by overdose on the edge Cheatle MD Pain Med 2011 Jun12 Suppl 2S43-8

Pain and suicidality insights from reward and addiction neuroscience Elman I Borsook D Volkow ND Prog Neurobiol 2013 Oct1091-27

Ilgen et al 2013

HR how often a particular event happens in one group compared to how often it happens in another group over time

The lifetime prevalence of suicide

attempts was between 5 and 14

in individuals with chronic pain with the prevalence of suicidal

ideation being approximately 20

(Tang and Crane 2006)

7 MGH Center for Law Brain and Behavior

Suic

ide

2 MGH Center for Law Brain and Behavior

Relative Status (Addiction and Pain) No Good Treatment for Chronic Pain

3 MGH Center for Law Brain and Behavior

Rela

tive

Stat

es

Drug War FAIL Drugs Now Kill More People Than Car Accidents httpthefreethoughtprojectcomopiates-killing-people-car-accidents

4 MGH Center for Law Brain and Behavior

Addi

ctio

n Pr

oble

m

MGH Center for Law Brain and Behavior 5

Pain

Pro

blem

25 Mill with severe pain 100 million with chronic pain 2 Mill on opioid addicts

6 MGH Center for Law Brain and Behavior

Rela

tive

Stat

es

Chronic pain costs US up to $635 billion Prescription Opioid Epidemic $78 billion

Depression chronic pain and suicide by overdose on the edge Cheatle MD Pain Med 2011 Jun12 Suppl 2S43-8

Pain and suicidality insights from reward and addiction neuroscience Elman I Borsook D Volkow ND Prog Neurobiol 2013 Oct1091-27

Ilgen et al 2013

HR how often a particular event happens in one group compared to how often it happens in another group over time

The lifetime prevalence of suicide

attempts was between 5 and 14

in individuals with chronic pain with the prevalence of suicidal

ideation being approximately 20

(Tang and Crane 2006)

7 MGH Center for Law Brain and Behavior

Suic

ide

3 MGH Center for Law Brain and Behavior

Rela

tive

Stat

es

Drug War FAIL Drugs Now Kill More People Than Car Accidents httpthefreethoughtprojectcomopiates-killing-people-car-accidents

4 MGH Center for Law Brain and Behavior

Addi

ctio

n Pr

oble

m

MGH Center for Law Brain and Behavior 5

Pain

Pro

blem

25 Mill with severe pain 100 million with chronic pain 2 Mill on opioid addicts

6 MGH Center for Law Brain and Behavior

Rela

tive

Stat

es

Chronic pain costs US up to $635 billion Prescription Opioid Epidemic $78 billion

Depression chronic pain and suicide by overdose on the edge Cheatle MD Pain Med 2011 Jun12 Suppl 2S43-8

Pain and suicidality insights from reward and addiction neuroscience Elman I Borsook D Volkow ND Prog Neurobiol 2013 Oct1091-27

Ilgen et al 2013

HR how often a particular event happens in one group compared to how often it happens in another group over time

The lifetime prevalence of suicide

attempts was between 5 and 14

in individuals with chronic pain with the prevalence of suicidal

ideation being approximately 20

(Tang and Crane 2006)

7 MGH Center for Law Brain and Behavior

Suic

ide

Drug War FAIL Drugs Now Kill More People Than Car Accidents httpthefreethoughtprojectcomopiates-killing-people-car-accidents

4 MGH Center for Law Brain and Behavior

Addi

ctio

n Pr

oble

m

MGH Center for Law Brain and Behavior 5

Pain

Pro

blem

25 Mill with severe pain 100 million with chronic pain 2 Mill on opioid addicts

6 MGH Center for Law Brain and Behavior

Rela

tive

Stat

es

Chronic pain costs US up to $635 billion Prescription Opioid Epidemic $78 billion

Depression chronic pain and suicide by overdose on the edge Cheatle MD Pain Med 2011 Jun12 Suppl 2S43-8

Pain and suicidality insights from reward and addiction neuroscience Elman I Borsook D Volkow ND Prog Neurobiol 2013 Oct1091-27

Ilgen et al 2013

HR how often a particular event happens in one group compared to how often it happens in another group over time

The lifetime prevalence of suicide

attempts was between 5 and 14

in individuals with chronic pain with the prevalence of suicidal

ideation being approximately 20

(Tang and Crane 2006)

7 MGH Center for Law Brain and Behavior

Suic

ide

MGH Center for Law Brain and Behavior 5

Pain

Pro

blem

25 Mill with severe pain 100 million with chronic pain 2 Mill on opioid addicts

6 MGH Center for Law Brain and Behavior

Rela

tive

Stat

es

Chronic pain costs US up to $635 billion Prescription Opioid Epidemic $78 billion

Depression chronic pain and suicide by overdose on the edge Cheatle MD Pain Med 2011 Jun12 Suppl 2S43-8

Pain and suicidality insights from reward and addiction neuroscience Elman I Borsook D Volkow ND Prog Neurobiol 2013 Oct1091-27

Ilgen et al 2013

HR how often a particular event happens in one group compared to how often it happens in another group over time

The lifetime prevalence of suicide

attempts was between 5 and 14

in individuals with chronic pain with the prevalence of suicidal

ideation being approximately 20

(Tang and Crane 2006)

7 MGH Center for Law Brain and Behavior

Suic

ide

25 Mill with severe pain 100 million with chronic pain 2 Mill on opioid addicts

6 MGH Center for Law Brain and Behavior

Rela

tive

Stat

es

Chronic pain costs US up to $635 billion Prescription Opioid Epidemic $78 billion

Depression chronic pain and suicide by overdose on the edge Cheatle MD Pain Med 2011 Jun12 Suppl 2S43-8

Pain and suicidality insights from reward and addiction neuroscience Elman I Borsook D Volkow ND Prog Neurobiol 2013 Oct1091-27

Ilgen et al 2013

HR how often a particular event happens in one group compared to how often it happens in another group over time

The lifetime prevalence of suicide

attempts was between 5 and 14

in individuals with chronic pain with the prevalence of suicidal

ideation being approximately 20

(Tang and Crane 2006)

7 MGH Center for Law Brain and Behavior

Suic

ide

Depression chronic pain and suicide by overdose on the edge Cheatle MD Pain Med 2011 Jun12 Suppl 2S43-8

Pain and suicidality insights from reward and addiction neuroscience Elman I Borsook D Volkow ND Prog Neurobiol 2013 Oct1091-27

Ilgen et al 2013

HR how often a particular event happens in one group compared to how often it happens in another group over time

The lifetime prevalence of suicide

attempts was between 5 and 14

in individuals with chronic pain with the prevalence of suicidal

ideation being approximately 20

(Tang and Crane 2006)

7 MGH Center for Law Brain and Behavior

Suic

ide

Common Brain Mechanisms of Chronic Pain and Addiction Elman I Borsook D Neuron 2016 Jan 689(1)11-36

8 MGH Center for Law Brain and Behavior

Neu

ral S

yste

ms

9

Decrease in Gray Matter Volume in

DLPC

Altered Brain Network

Connectivity

Structural Changes in

Nerve Tracts

Altered Brain Chemistry

Normal Brain

Chronic Pain Brain

Altered Behaviors Sensory (eg spontaneous pain at rest)

Affective (eg anxiety depression suicide addiction) Cognitive (eg decreased attention) Emotional (eg reward deficit state)

MGH Center for Law Brain and Behavior

00014

00012

00010

Amyg

dala

Vol

ume

(Nor

mal

ized)

Left Right

Opioid-Dependent Patients

Controls

p lt 005

Amygdala

Upadhyay at al 2010 Brain

10

1

MGH Center for Law Brain and Behavior

Stria Terminalis

p lt 005

p lt 0005

Corona Radiata

Opioid-Dependent Subjects

Control Subjects

Mean FA (Opioid-Dependent Subjects) Mean FA (Control Subjects)

FA

Whole Brain White Matter

03 06

123456789

10

Subj

ects

03 05

123456789

10

Uncinate Fasciculus

Subj

ects

FA

Single Subject DTI Data

Upadhyay at al 2010 Brain

11

2

MGH Center for Law Brain and Behavior

12

Interoception Fc with Anterior Insula

Reward Circuitry Fc Nucleus Accumbens

Upadhyay at al 2010 Brain

3

MGH Center for Law Brain and Behavior

Problem 1 No good treatment Problem 2 A suffering group (~ 100 million Americans) Problem 3 No Good Science that helps pain management CDC Guidelines Problem 4 Politics over Societal Well-being

13 MGH Center for Law Brain and Behavior

The

Clin

icia

ns D

ilem

ma

A patient long before becoming the subject of medical scrutiny is at first simply a storyteller a narrator of suffering-a traveler who has visited the kingdom of the ill To relieve an illness one must begin then by understanding the story The Emperor of All Maladies Siddhartha Mukherjee Prescription opioid addiction and chronic pain More than a feeling Ling W Drug Alcohol Depend 2017 Apr 1173 Suppl 1S73-S74

14 MGH Center for Law Brain and Behavior

I will apply for the benefit of the sick all measures which are required avoiding those twin traps of overtreatment and therapeutic nihilism

00014

00012

00010

Amyg

dala

Vol

ume

(Nor

mal

ized)

Left Right

Opioid-Dependent Patients

Controls

p lt 005

Amygdala

Upadhyay at al 2010 Brain

10

1

MGH Center for Law Brain and Behavior

Stria Terminalis

p lt 005

p lt 0005

Corona Radiata

Opioid-Dependent Subjects

Control Subjects

Mean FA (Opioid-Dependent Subjects) Mean FA (Control Subjects)

FA

Whole Brain White Matter

03 06

123456789

10

Subj

ects

03 05

123456789

10

Uncinate Fasciculus

Subj

ects

FA

Single Subject DTI Data

Upadhyay at al 2010 Brain

11

2

MGH Center for Law Brain and Behavior

12

Interoception Fc with Anterior Insula

Reward Circuitry Fc Nucleus Accumbens

Upadhyay at al 2010 Brain

3

MGH Center for Law Brain and Behavior

Problem 1 No good treatment Problem 2 A suffering group (~ 100 million Americans) Problem 3 No Good Science that helps pain management CDC Guidelines Problem 4 Politics over Societal Well-being

13 MGH Center for Law Brain and Behavior

The

Clin

icia

ns D

ilem

ma

A patient long before becoming the subject of medical scrutiny is at first simply a storyteller a narrator of suffering-a traveler who has visited the kingdom of the ill To relieve an illness one must begin then by understanding the story The Emperor of All Maladies Siddhartha Mukherjee Prescription opioid addiction and chronic pain More than a feeling Ling W Drug Alcohol Depend 2017 Apr 1173 Suppl 1S73-S74

14 MGH Center for Law Brain and Behavior

I will apply for the benefit of the sick all measures which are required avoiding those twin traps of overtreatment and therapeutic nihilism

Stria Terminalis

p lt 005

p lt 0005

Corona Radiata

Opioid-Dependent Subjects

Control Subjects

Mean FA (Opioid-Dependent Subjects) Mean FA (Control Subjects)

FA

Whole Brain White Matter

03 06

123456789

10

Subj

ects

03 05

123456789

10

Uncinate Fasciculus

Subj

ects

FA

Single Subject DTI Data

Upadhyay at al 2010 Brain

11

2

MGH Center for Law Brain and Behavior

12

Interoception Fc with Anterior Insula

Reward Circuitry Fc Nucleus Accumbens

Upadhyay at al 2010 Brain

3

MGH Center for Law Brain and Behavior

Problem 1 No good treatment Problem 2 A suffering group (~ 100 million Americans) Problem 3 No Good Science that helps pain management CDC Guidelines Problem 4 Politics over Societal Well-being

13 MGH Center for Law Brain and Behavior

The

Clin

icia

ns D

ilem

ma

A patient long before becoming the subject of medical scrutiny is at first simply a storyteller a narrator of suffering-a traveler who has visited the kingdom of the ill To relieve an illness one must begin then by understanding the story The Emperor of All Maladies Siddhartha Mukherjee Prescription opioid addiction and chronic pain More than a feeling Ling W Drug Alcohol Depend 2017 Apr 1173 Suppl 1S73-S74

14 MGH Center for Law Brain and Behavior

I will apply for the benefit of the sick all measures which are required avoiding those twin traps of overtreatment and therapeutic nihilism

12

Interoception Fc with Anterior Insula

Reward Circuitry Fc Nucleus Accumbens

Upadhyay at al 2010 Brain

3

MGH Center for Law Brain and Behavior

Problem 1 No good treatment Problem 2 A suffering group (~ 100 million Americans) Problem 3 No Good Science that helps pain management CDC Guidelines Problem 4 Politics over Societal Well-being

13 MGH Center for Law Brain and Behavior

The

Clin

icia

ns D

ilem

ma

A patient long before becoming the subject of medical scrutiny is at first simply a storyteller a narrator of suffering-a traveler who has visited the kingdom of the ill To relieve an illness one must begin then by understanding the story The Emperor of All Maladies Siddhartha Mukherjee Prescription opioid addiction and chronic pain More than a feeling Ling W Drug Alcohol Depend 2017 Apr 1173 Suppl 1S73-S74

14 MGH Center for Law Brain and Behavior

I will apply for the benefit of the sick all measures which are required avoiding those twin traps of overtreatment and therapeutic nihilism

Problem 1 No good treatment Problem 2 A suffering group (~ 100 million Americans) Problem 3 No Good Science that helps pain management CDC Guidelines Problem 4 Politics over Societal Well-being

13 MGH Center for Law Brain and Behavior

The

Clin

icia

ns D

ilem

ma

A patient long before becoming the subject of medical scrutiny is at first simply a storyteller a narrator of suffering-a traveler who has visited the kingdom of the ill To relieve an illness one must begin then by understanding the story The Emperor of All Maladies Siddhartha Mukherjee Prescription opioid addiction and chronic pain More than a feeling Ling W Drug Alcohol Depend 2017 Apr 1173 Suppl 1S73-S74

14 MGH Center for Law Brain and Behavior

I will apply for the benefit of the sick all measures which are required avoiding those twin traps of overtreatment and therapeutic nihilism

A patient long before becoming the subject of medical scrutiny is at first simply a storyteller a narrator of suffering-a traveler who has visited the kingdom of the ill To relieve an illness one must begin then by understanding the story The Emperor of All Maladies Siddhartha Mukherjee Prescription opioid addiction and chronic pain More than a feeling Ling W Drug Alcohol Depend 2017 Apr 1173 Suppl 1S73-S74

14 MGH Center for Law Brain and Behavior

I will apply for the benefit of the sick all measures which are required avoiding those twin traps of overtreatment and therapeutic nihilism

Cochrane Reports

Lynch and Watson 2006

Drug

Effi

cacy

15 MGH Center for Law Brain and Behavior

MMWR Morb Mortal Wkly Rep 2017 Mar 1766(10)265-269 doi 1015585mmwrmm6610a1 Characteristics of Initial Prescription Episodes and Likelihood of Long-Term Opioid Use - United States 2006-2015 Shah A Hayes CJ Martin BC Because long-term opioid use often begins with treatment of acute pain (1) in March 2016 the CDC Guideline for Prescribing Opioids for Chronic Pain included recommendations for the duration of opioid therapy for acute pain and the type of opioid to select when therapy is initiated (2) However data quantifying the transition from acute to chronic opioid use are lacking The largest increments in probability of continued use were observed after the fifth and thirty-first days on therapy the second prescription 700 morphine milligram equivalents cumulative dose and first prescriptions with 10- and 30-day supplies By providing quantitative evidence on risk for long-term use based on initial prescribing characteristics these findings might inform opioid prescribing practices

Drug

Dat

a

16 MGH Center for Law Brain and Behavior

MMWR Morb Mortal Wkly Rep 2017 Mar 1766(10)265-269 doi 1015585mmwrmm6610a1 Characteristics of Initial Prescription Episodes and Likelihood of Long-Term Opioid Use - United States 2006-2015 Shah A Hayes CJ Martin BC Because long-term opioid use often begins with treatment of acute pain (1) in March 2016 the CDC Guideline for Prescribing Opioids for Chronic Pain included recommendations for the duration of opioid therapy for acute pain and the type of opioid to select when therapy is initiated (2) However data quantifying the transition from acute to chronic opioid use are lacking The largest increments in probability of continued use were observed after the fifth and thirty-first days on therapy the second prescription 700 morphine milligram equivalents cumulative dose and first prescriptions with 10- and 30-day supplies By providing quantitative evidence on risk for long-term use based on initial prescribing characteristics these findings might inform opioid prescribing practices

Drug

Dat

a

16 MGH Center for Law Brain and Behavior

The findings of this systematic review suggest that proper management of a type of strong painkiller (opioids) in well-selected patients with no history of substance addiction or abuse can lead to long-term pain relief for some patients with a very small (though not zero) risk of developing addiction abuse or other serious side effects However the evidence supporting these conclusions is weak and longer-term studies are needed to identify the patients who are most likely to benefit from treatment

Evidence is insufficient to determine the effectiveness of long-term opioid therapy for improving chronic pain and function Evidence supports a dose-dependent risk for serious harms

The effectiveness and risks of long-term opioid therapy for chronic pain a systematic review for a National Institutes of Health Pathways to Prevention Workshop Chou R Turner JA Devine EB Hansen RN Sullivan SD Blazina I Dana T Bougatsos C Deyo RA Ann Intern Med 2015 Feb 17162(4)276-86

Opioids compared with placebo or other treatments for chronic low back pain an update of the Cochrane Review Chaparro LE Furlan AD Deshpande A Mailis-Gagnon A Atlas S Turk DC Spine (Phila Pa 1976) 2014 Apr 139(7)556-63

Drug

Dat

a

17 MGH Center for Law Brain and Behavior

Miti

gatio

n St

rate

gies

18 MGH Center for Law Brain and Behavior

3 to 4 of the adult population (96 million to 115 million persons) were prescribed longer-term opioid therapy

In 2014 alone US retail pharmacies dispensed 245 million prescriptions for opioid pain relievers

More than a third (37) of the 44000 drug-overdose deaths that were reported in 2013 (the most recent year for which estimates are available) were attributable to pharmaceutical opioids heroin accounted for an additional 19

Rela

tive

Stat

es

19 MGH Center for Law Brain and Behavior

1 Do opioids produce addiction in all pain patients 11 If yes what are the consequences 12 If no how do we deal with these patients

2 Data Data Data Where is it 21 Epidemiologic Data (doing better) 22 Research Data (doing better) 33 Public Policy (doing better)

3 What are the cost-benefit issues 31 pure drug free society - billions spent on the drug war 32 suffering in chronic pain 4 A National Imperative 41 What are the realistic timelines to new non-addictive medications for symptomatic Rx the clinic

20 MGH Center for Law Brain and Behavior

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lutio

ns

• Opioids for Chronic Pain Where is the Science for the Clinician
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3 to 4 of the adult population (96 million to 115 million persons) were prescribed longer-term opioid therapy

In 2014 alone US retail pharmacies dispensed 245 million prescriptions for opioid pain relievers

More than a third (37) of the 44000 drug-overdose deaths that were reported in 2013 (the most recent year for which estimates are available) were attributable to pharmaceutical opioids heroin accounted for an additional 19

Rela

tive

Stat

es

19 MGH Center for Law Brain and Behavior

1 Do opioids produce addiction in all pain patients 11 If yes what are the consequences 12 If no how do we deal with these patients

2 Data Data Data Where is it 21 Epidemiologic Data (doing better) 22 Research Data (doing better) 33 Public Policy (doing better)

3 What are the cost-benefit issues 31 pure drug free society - billions spent on the drug war 32 suffering in chronic pain 4 A National Imperative 41 What are the realistic timelines to new non-addictive medications for symptomatic Rx the clinic

20 MGH Center for Law Brain and Behavior

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lutio

ns

• Opioids for Chronic Pain Where is the Science for the Clinician
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1 Do opioids produce addiction in all pain patients 11 If yes what are the consequences 12 If no how do we deal with these patients

2 Data Data Data Where is it 21 Epidemiologic Data (doing better) 22 Research Data (doing better) 33 Public Policy (doing better)

3 What are the cost-benefit issues 31 pure drug free society - billions spent on the drug war 32 suffering in chronic pain 4 A National Imperative 41 What are the realistic timelines to new non-addictive medications for symptomatic Rx the clinic

20 MGH Center for Law Brain and Behavior

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lutio

ns

• Opioids for Chronic Pain Where is the Science for the Clinician
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