state of opioid use for treatment of chronic pain: role of ... · various opioids and during...
TRANSCRIPT
State of Opioid Use for Treatment of
Chronic Pain: Role of Targeted Drug
Delivery
David L. Caraway, M.D., Ph.D.
CEO, Medical Director
Center for Pain Relief, Tri-State
St. Mary’s Regional Medical Center
Huntington, WV
"Life is like riding a bicycle. To keep your balance you must keep moving." - Albert Einstein
Disclosures
Consultant, Investigator, and Faculty, Medtronic Inc.
Consultant, Spinal Modulation, Inc.
Consultant, Vertos Medical, Inc.
Bioness, Inc.
Leadership Positions
NANS
ASIPP
3
Beliefs Common to Americans
and Canadians
We won the War of 1812
We do not stereotype our cross border friends
We think their accent is odd
Our health care system is the best
There is solid evidence for efficacy and safety
supporting use of opioids for chronic non-cancer
pain
Where Were We in 2002?
• Pain is a destructive disease process that should
be treated (2001 JCAHO)
• It is not considered legal, ethical or good
medical practice to withhold opioids from
patients whose lives could be improved with
treatment
Ballantyne, South Med J. 2006;99(11):1245-1255.
Where Are We in 2013?
“American Pain Foundation Shuts Down as Senators
Launch Investigation of Prescription Narcotics”
“The Federation of State Medical Boards, The Joint
Commission (that made pain management a national
priority in 2001) as well as 5 major pain Societies
several prominent doctors , hospitals and
pharmaceutical companies have received demand
letters from the Senate Finance Committee”
(5/08/12 Washington Post)5.
Where Are We in 2012?
"These groups, these pain organizations … helped
usher in an epidemic that's killed 100,000 people by
promoting aggressive use of opioids,"
"What makes this especially disturbing is that despite
overwhelming evidence that their effort created a
public health crisis, they're continuing to minimize
the risk of addiction.”
(Dr. Andrew Kolodny, chairman of psychiatry at Maimonides Medical Center in
Brooklyn, N.Y., and president of Physicians for Responsible Opioid
Prescribing 5/08/12 Washington Post)5.
CDC on Opioids
November 1, 2011 : Dr. Thomas Frieden Director of
the Centers for Disease Control and Prevention
"For chronic pain, narcotics
should be the last resort."
.
8
U.S. with 4.6% of world’s population
Produces 80% of Lawyers (1 lawyer per 1.5
incarcerated) ABA
Consumes almost 30% of Global Oil supply
(CIA)
Consumes 80% of Global Opioid supply
Patricia Good, Division of Drug Diversion Control, DEA
Consumes 99% of Global Hydrocodone supply JAMA, 2007
Canadian Opioid Trends
“Canadians are among the highest users of prescription
opioids in the world, and overall usage of
prescription opioids has more than doubled over the
past decade.”
“As many as 200 000 Canadians are currently addicted
to painkillers, …he’s equally discouraged that
evidence-based best practices for treatment of
medically induced addiction do not exist.”
Benedikt Fischer and Jürgen Rehm, director of the Social and
Epidemiological Research Department at the Centre for
Addiction and Mental Health in Toronto, Ontario
Opioid Prescribing
What is your approach?
Will never prescribe Prescribe without
recognition of risks
Assessment of risk and
benefits guides prescribing
Balance
The Perfect Storm
Overdue recognition of pain as a
medical condition
• 1992 –2002: Population: up 13%, Controlled Rx 154%
• Aggressive marketing including “off-label” and to primary care doctors of potent new preparations
• Overdose Rx deaths exceeded heroin and cocaine first in 2002 . 4000 deaths from methadone in 2005
• 15,000 killed in 2008. 3 times more than in 1999 45% of people who died were Medicaid enrollees
• Nearly half million ED visits. Direct health care costs of up to $72.5 billion
• Nationwide prescription pain pills kills more people than guns (NRA: gun homicide rate)
Rates of prescription painkiller sales, deaths and
substance abuse treatment admissions (1999-2010)
Sources : National Vital Statistics System, 1999-2008; Automation of Reports and Consolidated
Orders System (ARCOS) of the Drug Enforcement Administration (DEA), 1999-2010;
Treatment Episode Data Set, 1999-2009 .
Source Where Pain Relievers Were Obtained for Most Recent Nonmedical Use among Past Year
Users Aged 12 or Older
Note: Totals may not sum to 100% because of rounding or because suppressed estimates are not shown.
1 The Other category includes the sources: “Wrote Fake Prescription,” “Stole from Doctor’s Office/Clinic/Hospital/Pharmacy,” and “Some Other Way.”
Bought/Took
from Friend/Relative
14.8%
Drug Dealer/
Stranger
3.9%
Bought on
Internet
0.1% Other 1
4.9%
Free from
Friend/Relative
7.3%
Bought/Took from
Friend/Relative
4.9%
One
Doctor
80.7%
Drug Dealer/
Stranger
1.6%Other 1
2.2%
Source Where Respondent Obtained
Source Where Friend/Relative Obtained
One Doctor
19.1%
More than
One Doctor
1.6%
Free from
Friend/Relative
55.7%
More than One Doctor
3.3%
Who Prescribes?
National Vital Statistics System. Drug overdose death rates by state. 2008.
Available from URL: http://www.cdc.gov/homeandrecreationalsafety/rxbrief/
CDC (Centers for Disease Control). Vital signs: overdoses of prescription opioid pain relievers—
United States, 1999-2008. MMWR. 2011;60:1-6.
CDC. Vital Signs: Overdoses of Prescription Opioid Pain Relievers—United States, 1999-2008. MMWR 2011; 60: 1-6. 7. Substance Abuse and Mental Health Services Administration.
Results from the 2010 National Survey on Drug Use and Health. Volume 1: Summary of National Findings. Rockville, MD: Substance Abuse and Mental Health Services
Administration, Office of Applied Studies; 2011. Available from URL: http://oas.samhsa.gov/NSDUH/2k10NSDUH/2k10Results.htm#2.16.
Substance Abuse and Mental Health Services Administration. Substance abuse treatment admissions by primary substance of abuse, according to sex, age group, race, and ethnicity 2009
(Treatment Episode Data Set). Available from URL: http://wwwdasis.samhsa.gov/webt/quicklink/US09.htm.
http://www.cdc.gov/homeandrecreationalsafety/rxbrief
Number ONE!
Huntington, WV:
• Fattest City (CDC 2006 and Jamie Oliver)
• WV number one prescriber of antibiotics (1222 per 1000 CDEEP 12/2011
• Highest Disability (21% SSA 2011,60 minutes 10/06/2013)
• Top 10 Saddest city (USA Today 2/28/2012)
• Cancer and diabetes deaths (CDC 2012)
• Highest Smoking Rate ( 26.8% CDC 2011)
• Highest adult edentulous rate (47.9 % CDC 1999)
WE have slipped to number two in one area
Drug overdose death rates by state per
100,000 people (2008)
SOURCE: National Vital Statistics System, 2008 :
SOURCE: Automation of Reports and Consolidated Orders System (ARCOS) of the Drug
Enforcement Administration (DEA), 2010
Amount of prescription painkillers
sold by state per 10,000 people (2010)
13.6%
12.7%
10.4%8.9%
6.5%
4.9%4.0%
0%
2%
4%
6%
8%
10%
12%
14%
16%
1999 2000 2001 2002 2003 2004 2005
Methadone Related Deaths
(% all Poisoning Deaths)
Source: CDC/NCHS, National Vital Statistics System.
Most abused
• Hydrocodone
– Most prescribed of all drugs
– Largest number of pills diverted
• Oxycontin
– Highest dollar amount of traffic
• Methadone
– Most deaths – Heroin now fast approaching
• Most commonly associated with opioid abuse
– Xanax, Soma
– ED visits for SOMA 15,830, in 2004 to 31,763 in 2009
Opioid Treatment in Nonterminal
Chronic Pain
Efficacy
Safety
Not Lawyers, insurance companies, drug reps
Chronic Pain Patients are Often
Not Satisfied with Opioids
Control Over Chronic Pain Impact on Quality of Life
2006 Voices of Chronic Pain Survey. (American Pain Foundation)
• Chronic pain patients have a “mixed” attitude toward opioids and few patients rated opioids as
“very effective” as way to control their chronic pain
• Many chronic pain patients also question the safety profile of opioids
• Short term efficacy
– Clear efficacy in multiple RCT’s (up to 8 months)
demonstrate improvement in pain
– No evidence to support dosing of higher than 180
mg morphine equivalent per day
• Long term efficacy
– No RCTs for longer than 8 months
– Overall evidence is weak
– Studies mostly look at VAS, little evidence of
improved function
Is Opioid Therapy Effective?
Ballantyne JC, Mao J. Opioid therapy for chronic pain. N Engl J
Med November 13, 2003;349:1943-53
APS /AAPM Opioid Guidelines
• In fact, the panel did not rate any of its 25
recommendations as supported by high quality
evidence.
• Only 4 recommendations were viewed as
supported by even moderate quality evidence.
• Nonetheless, the panel came to unanimous
consensus on almost all of its recommendations
[regarding opioids]
The Journal of Pain Volume 10, Issue 2 Pages
113-130.e22, February 2009
Chronic Non-Malignant Pain
• Moulin et al., Lancet 347:143-147, 1996
• Randomized, DB, crossover study, up to 120mg po MS
• 46 patients, average age 40 yrs.
Oral Opioid Approval
Mean Daily dose of Exalgo arm 37.8 mg Sources : FDA.
Oral Opioid Approval
Sources : FDA.
Dose Escalation
• Tolerance
– Physiological
• Opioid Induced Hyperalgesia
– Solid evidence in animal models
– Emerging clinical data
• Perception
– Goals of therapy
• Disease progression
Age Dependent Opioid Dose Escalation
in Chronic Pain Patients
• Retrospective chart review examined to see if
the age of the patient is related to dose
escalation
• Divided into two groups: < 50 vs > 60
• Younger 452 MMDE
• Older 211 MMDE
• Older VAS reduction from 6.9 to 5.6
• Younger unchanged Palmer et. al. Anesth
Analg 2005; 100:1740-5
Opioid Induced Hyperalgesia
Dose escalation may be a result of tolerance, opioid-induced hyperalgesia or both
• Presentation of Opioid Induced Hyperalgesia
– Associated with high dose and long term use of opioids (animal studies demonstrate single dose induction)
– Increased sensitivity to noxious stimuli
– Paradoxically, as medication is increased to relieve pain, patients experience more pain
– Some patients report decreased pain when taken off of opiates
Mechanisms of OIH• Pharmacological tolerance is a desensitization
• Opioid induced hyperalgesia is a sensitization
• Clinical approaches are different between these two processes
• NMDAr cellular mechanisms are common to both and also are involved in neuropathic pain
• Evidence NMDA receptor antagonists may attenuate OIH
• Opioid administration induces a pronociceptive process mediated in part by increased synthesis of excitatory neuropeptides (through spinal dynorphin which is
increased with opioid infusion)
King et al 2005, Mao 2006, Ossipov et al 2005
Mao J., Pain (100) 2002 213-217
Opioid Induced Hyperalgesia
Angst, MS & Clark, DJ: Opioid-induced hyperalgesia: A
qualitative systematic review. Anesthesiology 2006;
104:570–87
Opioid Induced Hyperalgesia
Conclusions:
• Solid support in animal models of OIH with
various opioids and during withdrawal
• Human data are far more limited and provide
only indirect evidence of OIH
“Conceivably, the long term use of opioids may
exacerbate rather than ameliorate chronic
pain”Angst, MS & Clark, DJ: Opioid-induced hyperalgesia: A qualitative
systematic review. Anesthesiology 2006; 104:570–87
Universal Precautions in Pain
Medicine
• Our understanding and assessment methods to select patient s
that might benefit from opioid therapy are imperfect at best. Lack
of rigorous guidelines
• “Gut” is often incorrect, frequently unfair and stigmatizing
• Standardized approach to the assessment and ongoing
management of all chronic pain patients
Gourlay DL, Heit HA, Almahrezi A. Universal precautions
in pain medicine: a rational approach to the
treatment of chronic pain. Pain Med 2005;6:107-112.
Undue Scrutiny
ASIPP Guidelines 2012
ASIPP Guidelines 2012 Part 1
ASIPP Guidelines 2012 Part 1
ASIPP Guidelines 2012 Part 1
ASIPP Guidelines 2012 Part 1
ASIPP Guidelines 2012 Part 1
ASIPP Guidelines 2012 Part 1
Guidelines for Appropriate
Prescribing
• History
– Obtain and review all records, prior to initiation of
opioid therapy
– Develop a detailed history. Must include any
impairment in function or ADL’s
– Ask specifically if the patient has ever abused or
diverted illicit drugs or prescription medication
– Previous narcotic use
– Caution with self-referred patients
Guidelines for Appropriate Prescribing
Physical Examination
Goal is to establish and document an etiology
reasonably consistent with pain complaints.
Do the findings warrant narcotic analgesia?
Look for warning signs
Establish any functional limitations or deficits
Treatment
Do not start narcotics until detailed history has been
obtained
Document failure of more conservative methods
Determine the minimum dose to maintain function
and ADL’s
Once stable continue to document improvement in
quality of life and compliance
Monthly refills, comprehensive follow-up
Physician remains in control of dosing
Guidelines for Appropriate Prescribing
Create a written narcotics agreement
Informed consent of risks including lack of efficacy
and addiction
Specific office policies, mandatory frequency of
visits
Single source of prescriptions, no changes in
amounts without office visit and rationale
Random DOA screening
Single pharmacy
Delineation of consequences if non-compliant, exit
strategy
Guidelines for Appropriate Prescribing
Summary for Appropriate Prescribing
• Perform and document history and PE, establish diagnosis –prior to initiation of opioids
• Document failure of non-opioid therapy
• Titrate to achieve goals within 6- 8 weeks of initiation of opioid therapy
• Establish and document attainment of goals
• Failure to achieve moderate stable dose warrants re-examination of treatment plan
– Opioid rotation (?)
– Discontinuation
– Surveillance, documentation of 4A’s
Documentation
The “Four A”s
– Analgesia (pain relief, attainment of goals)
– Activities of daily living (ADLs; functional
outcomes)
– Adverse effects (side effects)
– Aberrant drug-related behaviors (appropriate use and
adherence vs misuse or addiction-related outcomes).
Placebo
AVINZA 30 QAM
AVINZA 30 QPM
MSC 15 BID
Double-Blind Study Results: Sleep Measures
Osteoarthritic (OA) Pain
Improved Overall Quality of Sleep
Ch
ang
e fr
om
Bas
elin
e (m
m)
Week 1 Week 40
5
10
15
20* †
*
* †
*
Quality of sleep assessed on a 100 mm scale and duration of sleep each night assessed on a 12-pt scale.Positive changes are improvements from baseline. ANOVA (P<0.05); *Significant difference from placebo (P0.05); †Significant difference from MS Contin®.
16. Caldwell JR, Rapoport RJ, Davis JC, et al. Efficacy and safety of a once-daily morphine formulation in chronic, moderate-to-severe osteoarthritis pain; results from a randomized placebo-controlled, double-blind trial and an open-label extension trial. J Pain Symptom Management. 2002;23:278-291.
Opioid Therapy: “Rescue Dosing”
• Long-acting opioid “around-the-clock” plus a
short-acting opioid “rescue” dose “PRN”
– Preferred approach for patients with cancer pain
– Rescue dose may or may not be appropriate for
all patients, depending on syndrome and ability
to use the drug responsibly
– Rescue is 5%-15% of total daily dose
Portenoy RK. Opioid prescribing to patients with and without chemical dependency. Presented at: The International Conference on Pain and Chemical Dependency; June 6-8, 2002: New York, NY.
Intermittent Opioids
• Chronic use of opioids leads to tolerance and
possibly opioid induced hyperalgesia
• Intermittent use may reduce this problem (1)
• Allowing three days or more in between opioid
dosing may avoid dose escalation
• Use opioids only for “rescue” and activity
related pain, especially in the younger age
groups
1. Mao J., Pain (100) 2002 213-217
Intrathecal Opioids
• Intrathecal drug delivery devices are not a
therapy: They are a delivery system for a
therapy.
• Opioids are the therapy (for pain)
• How does the intrathecal route of delivery
compare to systemic in terms of safety, efficacy,
side effects and cost?
Ability to Discontinue Multiple Routes of Delivery
Why use the term“TARGETED DRUG DELIVERY”?
Systemic analgesia
• Distributes drug via blood
stream
• High blood levels of drug
• Brain receives highest
proportion of drug
• High dose of drug required
– High elimination load
• Increase in systemic side
effects
Spinal analgesia
• Intrathecal drug distribution
• Low blood levels of drug
• Most drug binds to
TARGET (spinal cord pain
receptors)
• Low dose of drug is effective
– Low elimination load
• Minimal systemic effect on
brain and gut 59
Diversion—Eliminate Easy Access
Intrathecal Opioids
Advantages:
• Achieves steady-state, around the clock dosing
• Reduced side effects (1), Use of intermittent
dosing to reduce tolerance
• Intrathecal Adjuvants
• Compliance : Eliminate systemic opioids
– Can provide patient activated rescue dosing (PCA)
– Reduction in longitudinal costs
1. Smith, T. J Clin Oncology, 2002
Intrathecal Opioids
Disadvantages:
• More invasive
• More difficult to discontinue therapy
• Acquisition costs
• If positioned as a salvage therapy for patients
who have failed but remain on high dose
systemic opioids outcomes are diminished
Practice of David Caraway, MD. St. Mary’s Regional Medical Center
Huntington, WV.
Redefine Patient Selection
Easy first choices for PUMP
• Cancer pain
• Failed Back Pain and extremity pain - non responsive to SCS
• Elderly axial spinal pain
• Good analgesia with systemic opioids but intolerable side effects
Practice of David Caraway, MD. St. Mary’s Regional Medical Center Huntington, WV.
Kevin W.
Receiving
Medtronic
intrathecal drug
delivery for
chronic pain.
Redefine Patient Selection
Difficult choices for PUMP
• High oral opioid use with minimal perceived benefit
• Minimal baseline pain with intermittent severe pain may need specialized trialing (PTM?)
• Poorly defined etiology
• Poor compliance to previous therapies
• Young age
Practice of David Caraway, MD. St. Mary’s Regional Medical Center Huntington, WV.
Patient Selection for IDD
• Some conditions have not experienced good
outcomes:
– Headache
– Fibromyalgia
– Atypical facial pain
– Non-cancer head-neck pain
– Borderline personality
Typical Dosing
Typical Dosing
Pain Level
Dosing with self administered
PCA
Minimal DosingPain Level
Data Reveals Patient Satisfaction
and Reduction in Oral Opioids
• A prospective registry of 168 patients (92% NMP) using PCA (patient controlled analgesia) found1:
– Patients use device regularly
– Average number of boluses per day = 1.3
– 82% preferred PCA vs their previous method
– 75% more satisfied with PTM compared to their pump alone
– Reduced need for oral opioids
Ilias W, le Polain B, Buchser E, Demartini L; theoPTiMa study group. Patient controlled
analgesia in chronic pain patients: experience with a new device designed to be used with
implanted programmable pumps.Pain Pract. 2008;8(3):164-170.
Requires Same Strategies as
Systemic Delivery • Early titration to achieve
analgesia and therapy goals
• Careful consideration of
dose increases
• Maintain moderate doses
• Monitor for side effects,
efficacy
• Physician remains in control
of dosing
Psychological Evaluation
• Consider recommendations and treat if indicated - prior to trial
• Ability to understand appropriate expectations
• Has patient come to terms with status, expected life span
• Is this someone you are willing to “marry”?
• Major active psychosis, current drug addiction, some personality
disorders, cognitive deficits, progressive organic brain disorders,
suicidal, homicidal behavior
Know
When
To Quit
Dr.
Caraway
And…
When never
to start!
THE END
THANK
YOU