Presentation was originally done at Group Health Cooperative’s National Summit on Opioid Safety: http://www.ghinnovates.org/?p=3502 Presentation by: Jane C. Ballantyne, MD FRCA, with the Department of Anesthesiology and Pain Medicine at UW Medicine.

1. Principles for more cautious and
selective opioid prescribing for
chronic non-cancer pain
JANE C. BALLANTYNE MD FRCA
DEPARTMENT OF ANESTHESIOLOGY AND
PAIN MEDICINE

2. Silas Weir Mitchell in
“Characteristics”, an
autobiographical account of
his experience treating
injured soldiers after the
Civil War, 1866
If any man want to learn sympathetic charity, let him keep pain subdued for six
months by morphia, and then make the experiment of giving up the drug. By
this time he will have become irritable, nervous and cowardly. The nerves,
muffled, so to speak, by narcotics, will have grown to be not less sensitive but
acutely, abnormally capable of feeling pain, and of feeling as pain a multitude
of things not usually competent to cause it.

3. 20th century and a new moral imperative
 Caution persisted throughout most of the century
 Until the 1980s, the teaching was that opioids did
not work well for chronic pain, and addiction risk
was unacceptably high
 Change came about for two reasons:
 Palliative care specialists believed that chronic pain was
equally deserving of treatment with strong analgesics and that
existence of pain somehow protected against addiction
 Pharmaceutical industry developed and aggressively promoted
„designer‟ opioids

4. 2003
 No support in the literature for using high doses
 High doses associated with sensitization (hyperalgesia)
as well as desensitization (tolerance)
 High doses associated with endocrine and immune
consequences

5. Current evidence
Observational Epidemiological
 Clinical case series and open label  For wider population, analgesic
follow up studies support efficacy effectiveness is not substantiated
and safety of opioids
 Function of opioid treated patients seems
poor, opioid treated pain patients are less
 Generally doses are low to likely to work than non-treated matched
moderate and length of treatment cohorts
is 1-2 yrs, pain relief is partial
 Lack of safety of opioids has been
revealed, especially for high doses (death,
 No conclusion on function or fracture, endocrine effects)
quality of life
 Beginning to understand how many dose
escalate (most of those that stay on)
 Many people who are started on
opioids discontinue either because
 Beginning to understand who dose
of adverse effects or inadequate escalates (adverse selection)
pain relief

6. Is the difference a reflection of duration and dose?
Short term effectiveness Longer term effectiveness
 After a reasonable trial of non-opioid
and non-pharmacological treatments,  3 yrs later her dose has been escalated
she is started on opioids multiple times, usually after adverse
life events
 6 months later pain and function have
improved  She no longer has good pain relief, has
stopped working, and no dose is
enough

7. Why populations look worse than published cohorts
Cohort of patients who Population of patients at a
start on opioids given time point
Do well Do well
Unknown Unknown
Do bady Do badly
Come off Come off

8. Charles Alexander Bruce “Report
on the Manufacture of Tea and on
the extent and produce of the tea
plantations in Assam”
Calcutta, 1839. This Scottish
superintendent of tea culture in Assam
pleads for the cessation of poppy culture
and the prohibition of opium imports.
This vile drug has kept, and does now keep down the population: the women
have fewer children than those of other countries, and the children…in
general die at manhood; very few old men being seen in this unfortunate
country in comparison with others. Would it not be the highest of blessings, if
our humane and enlightened Government would stop these evils by a single
dash of the pen, and save Assam, and all those who are about to emigrate into
it as Tea cultivators, from the dreadful results attendant on the habitual use
of Opium? We should in the end be richly rewarded by having a fine healthy
race of men growing up for our plantations, to fell our forests. This can never
be affected by the feeble opium-smokers of Assam, who are more effeminate
than women.

9. Longer duration and higher dose associated with
 Higher rates of overdose and death
 Less likelihood of being able to wean if necessary
 Difficulty controlling acute pain, surgical recovery, terminal pain
 Continued use during pregnancy – neonatal abstinence
 Higher rates of mental health & substance use disorder, less able to
control usage
 Higher rates of falls and fractures in the elderly
 Less likelihood of returning to function or work
 Higher rates of endocrinopathy affecting fertility, libido & drive
 Higher rates of immune dysfunction
1. Dunn KM, Saunders KW, Rutter CM, et al. Ann Intern Med. Jan 19 2010;152(2):85-92.
2. Martin BC, Fan MY, Edlund MJ et al J Gen Intern Med. Dec 2011;26(12):1450-1457.
3. Miller M, Sturmer T, Azrael D et al J Am Geriatr Soc. Mar 2011;59(3):430-438.
4. Darnall BD, Stacey BR. Arch Intern Med. Mar 12 2012;172(5):431-432.
5. Afsharimani B, Cabot P, Parat MO. Cancer Metastasis Rev. Jun 2011;30(2):225-238.
6. Tavare AN, Perry NJ, Benzonana LL, Takata M, Ma D. . Int J Cancer. Mar 15 2012;130(6):1237-1250.

10. Principles for more cautious and
selective opioid prescribing for
chronic non-cancer pain
First major principle
For 90% chronic pain presenting to primary
care physicians, medical approaches are
often unsatisfactory
Second major principle
Opioids do not have proven efficacy or safety
at high doses or for prolonged usage

11. First major principle
Medical approaches are often
unsatisfactory
Recognition of this is the cultural
change needed

13. “The problem of
unrelieved pain remains
as urgent as ever.”
“At least 100 million
Americans suffer from
chronic pain, costing up
to $635 billion annually
in treatment and lost
productivity.”
“In the committee‟s
view, addressing the
nation‟s enormous
burden of pain will
require a cultural
transformation in the
way pain is
understood, assessed, an
Cultural transformation?
d treated.”

14. Cultural transformation needed is demedicalization of the
most common pain conditions
OLD PATHWAY NEW PATHWAY

15. Treating chronic pain
 Chronic pain is never simple
 Use measurement tools as a means of understanding
the scope of the problem
 eg PHQ-9, GAD, ORT
 Primary treatments for chronic pain
i. Motivation/activation/self-help
ii. Counseling
 Secondary treatments for chronic pain
i. Low risk analgesics (eg gabapentin)
ii. Psych meds for depression/anxiety/PTSD

16. Second major principle
Opioids have proven efficacy and (relative)
safety for the treatment of acute pain and
pain at the end of life
Opioids do not have proven efficacy and safety
for the treatment of pain long-term
1.Ballantyne JC, Shin N.S. Clin J Pain. 2008;24(6):469-478.
2.Ballantyne JC. Data review presented to FDA May 30th and 31st 2012. 2012.
3.Noble M, Treadwell JR, Tregear SJ, et al. Cochrane Database Syst Rev. 2010(1):CD006605.
4.Eriksen J, Sjogren P, Bruera E, et al Pain. 2006 2006;125:172-179.
5.Dillie KS, Fleming, M.F., Mundt, M.P., French, M.T. J Am Board Fam Med. 2008;21(2):108-117.
6.Toblin RL, Mack KA, Perveen G, Paulozzi LJ. Pain. Jun 2011;152(6):1249-1255.

17. Lack of supportive evidence for efficacy and safety underlies
the need to reserve opioids for serious pain
What is serious pain?
 Pain with a clear pathoanatomic or disease basis
 Underlying cause is disabling
 Cannot be improved by primary disease treatment or lifestyle
changes (eg elderly, disabled)
 Goal of pain treatment is comfort
 All other treatments (best efforts) have failed
1.Chou R, Fanciullo GJ, Fine PG, et al. Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain.
J Pain. Feb 2009;10(2):113-130.
2.Sullivan MD, Ballantyne JC. What are we treating with chronic opioid therapy? Arch Int Med. 2012;172(5):433-434.

18. 90 days is a key point
 90 days is often used in definitions of chronic pain
 Studies show that after 90 days continuous
use, opioid treatment is more likely to become life-
long
 Studies show that patients who continue opioids >
90 days tend to be high risk patients
1.Turk DC, Okifuji A. Pain terms and taxonomies. In: Bonica's Management of Pain (4th ed).
2.Braden JB, Fan MY, Edlund MJ et al J Pain. Nov 2008;9(11):1026-1035.
3.Korff MV, Saunders K, Thomas Ray G, et al. Clin J Pain. Jul-Aug 2008;24(6):521-527.
4.Martin BC, Fan MY, Edlund MJ et al J Gen Intern Med. Dec 2011;26(12):1450-1457.
5.Volinn E, Fargo JD, Fine PG. Pain. Apr 2009;142(3):194-201.

19. You get to 90 days
Is the patient a suitable candidate for opioids?
BENEFIT RISK
 Intractable pain-  Substance abuse Hx
producing disease  Family Hx sub abuse
 Childhood sexual abuse
 Goal is comfort  PTSD
 Anxiety
1.Sullivan MD, Ballantyne JC. Arch Int Med. 2012;172(5):433-434.  Depression
2.Martin BC, Fan MY, Edlund MJ et al J Gen Intern Med. Dec
2011;26(12):1450-1457.
3.Schwartz AC, Bradley R, Penza KM, et al. Psychosomatics. Mar-  Other MHD
Apr 2006;47(2):136-142.
4.Seal KH, Shi Y, Cohen G et al JAMA. 2012;307(9):940-947.

20. Principles of chronic opioid therapy
Expect it to be time consuming and
resource heavy

21. If the choice is to continue
 Develop clear understanding of risks and benefits (use care
agreement)
 Use single prescriber, single pharmacy
 Regular pick up
 Monitor
 Pain and function
 Psych status
 Prescription monitoring service (if available)
 UDTs
 Continue counseling
1.Chou R, Fanciullo GJ, Fine PG, et al. Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain. J Pain. Feb
2009;10(2):113-130.
2.Source: Agency Medical Directors‟ Group http://www.agencymeddirectors.wa.gov/Files/OpioidGdline.

22. General principles for dosing
 At treatment initiation, establish effective dose
 Start with short-acting, taken as needed
 Dose escalation may be needed to overcome
tolerance, but should be modest
 Doses > 100 mg morphine or morphine equivalence
require close scrutiny because safety is markedly
compromised at this dosing level
 Long-acting opioids are less useful because of
tolerance, may be indicated for „maintenance‟
1.Martin BC, Fan MY, Edlund MJ et al J Gen Intern Med. Dec 2011;26(12):1450-1457.
2.Edlund MJ, Martin BC, Fan MY et al Drug Alcohol Depend. Nov 1 2010;112(1-2):90-98.
3.Saunders KW, Dunn KM, Merrill JO, et al. J Gen Intern Med. Apr 2010;25(4):310-315.
4.Von Korff M, Merrill JO, Rutter CM et al Pain 2011;152:1256-62

23. Doses > 100 mg MED are a red flag
 Pain is not responsive
 Insurmountable tolerance
(no dose is enough)
 Difficulty controlling use
 Misuse 1.Morasco BJ, Duckart JP, Carr TP et al
Pain. Dec 2010;151(3):625-632.
 Addiction 2.Edlund MJ, Martin BC, Fan MY et al
Drug Alcohol Depend. Nov 1 2010;112(1-
2):90-98.
 Diversion 3.Weisner CM, Campbell CI, Ray GT, et
al. Pain. Oct 2009;145(3):287-293.

24. SUMMARY
Basic principles for cautious opioid prescribing
 Opioids do NOT have proven efficacy and safety for
treating chronic pain
 Opioids are powerful drugs and should be reserved
for serious pain
 Chronic pain is never simple – approach holistically
 Measurement based care is the new gold standard
 Chronic opioid therapy is not a simple solution;
expect it to be time and resource heavy
 90 days is a key point for reassessment
 > 100 mg MED is a red flag

25. Tightening the lid on pain prescriptions
Barry Meier, NYT April 8 2012
Few programs are in place to deal with patients now on
high opioid dosages who are not benefiting from them. If
the patients were taken off the medications, many would
experience severe withdrawal or have to take addiction
treatment drugs for years. Even avid believers in the new
direction, like Dr. Ballantyne, suggest that it might be
necessary to keep those patients on the opioids and to
focus instead on preventing new pain patients from getting
caught in the cycle.
“I think we are dealing with a lost generation of patients,”
she said.