pain management and addiction medicine russell k. portenoy, md chairman, department of pain medicine...
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Pain Management and Addiction Medicine
Pain Management and Addiction Medicine
Russell K. Portenoy, MDChairman, Department of Pain Medicine and
Palliative CareGerald J. Friedman Chair in Pain Medicine
and Palliative CareBeth Israel Medical Center
Professor of Neurology and AnesthesiologyAlbert Einstein College of Medicine
New York, New York
Pain Management and Addiction Medicine
Pain Management and Addiction Medicine
Role of opioid therapy in pain management
Risk management during opioid therapy for pain
Other issues– New formulations
33
Opioid Therapy: 2011Opioid Therapy: 2011
Acute pain
– International consensus that opioid therapy is first line for l consensus that opioid therapy is first line for moderate to severe acute painmoderate to severe acute pain
Chronic pain related to Chronic pain related to activeactive cancer or other cancer or other advanced illnessadvanced illness
– International consensus that opioid therapy is first line for l consensus that opioid therapy is first line for moderate to severe painmoderate to severe pain
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Opioid Therapy: 2011Opioid Therapy: 2011
Long-term opioid therapy for so-called chronic non-cancer pain
– Pain specialists agree that long-term opioid therapy is safe and effective for some patients
– Risks are significant and must be understood and managed
– No consensus about the positioning of this therapy, patient selection, or treatment guidelines
Chronic Pain: Immense Public Health Problem
Chronic Pain: Immense Public Health Problem
Persistent pain in primary care: WHO Study
– 5438 primary care patients from 15 sites in 14 countries assessed by interview and questionnaires
– 22% had persistent pain (>6 months + care or disability)• More likely to have anxiety or depressive disorder
(OR=4.14)
– Pain-distress relationships were more consistent across cultures than pain-disability
Gureje et al, JAMA, 1998:280:147
Chronic Pain: Immense Public Health Problem
Chronic Pain: Immense Public Health Problem
Approach to the Patient with Chronic Pain
Approach to the Patient with Chronic Pain
Pain Assessment
Comorbidities
Primary Therapy? Symptomatic Therapies?
Pharmacotherapy Other Approaches Opioids Interventional Nonopioid Rehabilitative
“Adjuvant PsychologicAnalgesics” Neurostimulatory
CAM
Etiology
Key Issue in Positioning Opioid Therapy: Effectiveness
Key Issue in Positioning Opioid Therapy: Effectiveness
Many RCTs and systematic reviews yield mixed findings and provide little help in developing evidence-based therapy
Key Issue in Positioning Opioid Therapy: Effectiveness
Key Issue in Positioning Opioid Therapy: Effectiveness
Opioids for chronic noncancer pain
Meta-analysis of RCTs through May, 2005 41 RCTs (N=6019) of any oral opioid therapy for
any type of pain, with study duration averaging 5 weeks (range 1-16)
Opioids outperformed placebo for pain and functional outcomes in nociceptive and neuropathic pain, and fibromyalgia
“Strong” opioids were superior to naproxen and nortriptyline only for pain relief
Furlan AD et al., CMAJ. 2006 May 23;174(11):1589-94
Key Issue in Positioning Opioid Therapy: Effectiveness
Key Issue in Positioning Opioid Therapy: Effectiveness
Opioids for chronic noncancer pain
Conclusion: There is short-term efficacy for pain and function in all types of pain; opioids are better than other drugs for pain, but not functional outcomes. There are insufficient data to judge long-term outcomes.
Furlan AD et al., CMAJ. 2006 May 23;174(11):1589-94
Key Issue in Positioning Opioid Therapy: Effectiveness
Key Issue in Positioning Opioid Therapy: Effectiveness
Opioid treatment for chronic back pain
Systematic review and meta-analysis through 2005
Studies of oral, topical, or transdermal opioids for chronic back pain, with study duration less than 16 weeks
Meta-analysis of 4 studies of opioids vs. placebo or nonopioid did not show efficacy (p=0.136)
Meta-analysis of 5 studies of different opioids did not show reduced baseline pain (p=0.055)
Abuse behaviors ranged from 5% to 24% Martell BA et al.Ann Intern Med. 2007;146:116-27
Key Issue in Positioning Opioid Therapy: Effectiveness
Key Issue in Positioning Opioid Therapy: Effectiveness
Opioid treatment for chronic back pain
CONCLUSIONS: Opioids have limited, if any, short-term value in chronic low back pain. Evidence about substance abuse is too limited to draw any conclusions. There are insufficient data to judge long-term outcomes.
Martell BA et al.Ann Intern Med. 2007;146:116-27
Opioids for noncancer pain: surveys
Systematic review of open-label prospective studies through April, 2007
17 studies (N=3079) of oral, transdermal or neuraxial opioid, with study duration at least 6 months
Many patients stopped treatment due to AEs or poor response (oral 32.5%, transdermal 17.5%, neuraxial 6.3%)
Signs of addiction in 0.05%; abuse in 0.43% Small but significant pain reduction for oral therapy (mean
1.99 points) and neuraxial therapy (mean 1.33 points); too few data to judge transdermal
Noble M et al., JPSM. 2008;35:214-228
Key Issue in Positioning Opioid Therapy: Effectiveness
Key Issue in Positioning Opioid Therapy: Effectiveness
Opioids for noncancer pain: surveys
Conclusion: Many patients stop therapy but there is weak evidence that those who continue have pain relief over time. There are insufficient data to judge other long-term outcomes, including function and drug abuse.
Noble M et al., JPSM. 2008;35:214-228
Key Issue in Positioning Opioid Therapy: Effectiveness
Key Issue in Positioning Opioid Therapy: Effectiveness
Key Issue in Positioning Opioid Therapy: Effectiveness
Key Issue in Positioning Opioid Therapy: Effectiveness
Conclusions– RCTs suggest efficacy but have very limited
relevance to long-term therapy – Observational studies provide weak evidence
that many patients stop therapy due to side effects or poor response, but those who continue may benefit
– Other outcomes, including those related to risk, are poorly characterized
Positioning Opioid TherapyPositioning Opioid Therapy
Despite limited evidence, APS-AAPM evidence-based guidelines: – Support consideration of an opioid trial for all
patients with severe pain, but case-by-case decision based on an analysis:
• What is conventional practice?• Are there reasonable alternatives?• Is there relatively high risk of adverse effects?• Is the patient likely to be a responsible drug-taker?
Chou R et al. J Pain 2009;10:113-130
Positioning Opioid TherapyPositioning Opioid Therapy
Trends over two decades– Rapid increase in opioid use by pain
specialists and primary care physicians– Rapid increase in adverse outcomes
• Abuse, addiction and diversion• Unintentional overdose
– Evolving responses by the• Clinical community• Regulatory and law enforcement communities
Trends in Long-Term Opioid Use
Trends in Long-Term Opioid Use
Study of health care claims data– From 1997 to 2005, age-gender groups had an
increased • incidence of long-term opioid use by 16% to 87% • prevalence of long-term opioid use by 61% to 135%
– Women used more opioids than men and older women had the highest prevalence (8%-9%)
– Sedative-hypnotics commonly used with opioids
Campbell CI et al.Am J Public Health 2010;100:2541-7
Trends in Opioid Use: Patients with SUD
Trends in Opioid Use: Patients with SUD
Study of health care claims data – From 1997 to 2005, prevalence of long-term opioid use
• Increased from 7.6% to 18.6% in patients with SUD• Increased from 2.7% to 4.2% in those w/o SUD• Dx of opioid disorder among those treated increased from
15.7% to 52.4%• Those with prior SUD received higher doses, more Schedule
II and long-acting opioids, and more sedative-hypnotics
Weisner, et al. Pain 2009;145:287-93.
Trends in Opioid Use: Commercial vs M’CaidTrends in Opioid Use: Commercial vs M’Caid
Study of health care claims data in a MCO and a Medicaid population – In 2000, chronic opioid therapy
• MCO population: 8% in those with mental health disorder (MHD) or SUD vs 3% w/o MHD or SUD
• Medicaid: 20% with MHD or SUD vs 13% w/o MHD or SUD
– From 2000 to 2005, chronic opioid therapy• MCO population: increased 34.9% in those with MHD or SUD vs. 27.8%
w/o MHD or SUD• Medicaid: increased 55.4% in those with MHD or SUD vs. 39.8% w/o
MHD or SUD
Edlund MJ, et al. Clin J Pain. 2010;26(1):1-8
Trends in Risk: Increasing Prescription Drug Abuse Trends in Risk: Increasing Prescription Drug Abuse
National HouseholdSurvey
On Drug Use and Health
Drug Abuse Warning Network
New Illicit Drug Use in the United States: 2005
New Illicit Drug Use in the United States: 2005
SAMHSA. Results From the 2005 National Survey on Drug Use and Health. DHHS Publication No. SMA 06-4194, 2006.
*526,000 new nonmedical users of OxyContin®.
Pain Relievers*
Tranquilizers Cocaine Ecstasy LSD PCP
Marijuana Inhalants Stimulants Sedatives Heroin
77108243247
615647
872877
1286
21142193
0
500
1000
1500
2000
2500
Nu
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ers
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Source of Opioids for Nonmedical Use Reported by Users
Source of Opioids for Nonmedical Use Reported by Users
*Source of drugs for the most recent nonmedical use of pain relievers reported by persons aged 12 or older in the United States 2005.SAMHSA. Results From the 2005 National Survey on Drug Use and Health. DHHS Publication No. SMA 06-4194, 2006.
59.8
16.8
4.30.8
0
10
20
30
40
50
60
70
Friend/Relative One Doctor Dealer/Stranger Internet
Pe
rce
nt
Management of Risk Is a “Package Deal”
Management of Risk Is a “Package Deal”
Best practice requires – Skills to optimize pharmacological outcomes– Skills to minimize risk
Risk is defined– Side effects– Abuse, addiction and diversion– Unintentional overdose
Management of Risk Is a “Package Deal”
Management of Risk Is a “Package Deal”
Understanding laws and regulations Screening & risk stratification: “Universal
Precautions’ Compliance monitoring commensurate with
risk stratum Dealing with problems over time Education about drug storage & sharing
Risk: Laws and RegulationRisk: Laws and Regulation
Federal: Controlled Substances Act– Prescribing is legal if it is consistent with
• Usual professional practice• Legitimate medical purpose
– Must stop prescribing if diversion occurs State criminal statutes concerned with diversion:
role for prescription monitoring programs State civil laws/regulations concerned with
physician practice
Prescription Monitoring Programs
Prescription Monitoring Programs
Practical Considerations in Risk Management
Practical Considerations in Risk Management
Patient selection based on assessment Distinguishing a trial from long-term therapy Stratifying risk Structuring therapy commensurate with risk Educating Assessing appropriate outcomes Adjusting over time Document and communicate
Stratify RiskStratify Risk
Gourlay DL, et al. Pain Med. 2005;6:107-112.
♦No past/current history of substance abuse
♦Noncontributory family history of substance abuse
♦No major or untreated psychological disorder
♦History of treated substance abuse
♦Significant family history of substance abuse
♦Past/comorbid psychological disorder
♦Active substance
abuse
♦Active addiction
♦Major untreated psychological disorder
♦Significant risk to self and practitioner
Low Risk Moderate Risk High Risk
Measures for ScreeningMeasures for Screening
CAGE AID Opioid Risk Tool SOAPP Many others
Structuring Therapy Based on Risk
Structuring Therapy Based on Risk
May include– Written agreement – Frequent visits– Prescribing small quantities– Long-acting drugs with no rescue doses
– One pharmacy
– Pill counts, no replacements or early scripts
– Urine toxicology screening
– Coordination with addiction medicine specialist, psychotherapist, others
Structuring Therapy: Role of Urine Drug Screening
Structuring Therapy: Role of Urine Drug Screening Low threshold for urine drug screening
Urine Toxicology Aberrant Behaviors
Yes No Total
Positive 10 (8%) 26 (21%) 36 (29%)
Negative 17 (14%) 69 (57%) 86 (71%)
Total 27 (22%) 95 (78%) 122
Katz N, Fanciullo GJ. Clin J Pain. 2002;18:S76-S82.
Opioid Therapy: Monitoring Outcomes
Opioid Therapy: Monitoring Outcomes
Critical outcomes: The 4 A’s– Analgesia– Adverse effects– Activities– Aberrant drug-related behaviors
Monitoring Aberrant Drug-taking Behaviors
Monitoring Aberrant Drug-taking Behaviors
Probably more predictive
– Selling prescription drugs– Prescription forgery– Stealing or borrowing another
patient’s drugs– Injecting oral formulation– Obtaining prescription drugs from
non-medical sources– Concurrent abuse of related illicit
drugs– Multiple unsanctioned dose
escalations– Recurrent prescription losses
Probably less predictive
– Aggressive complaining about need for higher doses
– Drug hoarding during periods of reduced symptoms
– Requesting specific drugs– Acquisition of similar drugs from
other medical sources– Unsanctioned dose escalation
1–2 times– Unapproved use of the drug to
treat another symptom– Reporting psychic effects not
intended by the clinician
Passik and Portenoy, 1998.
Aberrant Behaviors (n = 388)Aberrant Behaviors (n = 388)
55.4
25.3
8.5 6.74.1
0
10
20
30
40
50
60
0 2 to 3 3 to 4 5 to 7 8+
(n = 215)
(n = 98)
(n = 33) (n = 26)(n = 16)
Number of Behaviors Reported
Patie
nts
Exhi
bitin
g B
ehav
iors
(%)
(Passik, Kirsh et al, 2005)(Passik, Kirsh et al, 2005)
Unintentional OverdoseUnintentional Overdose
Factors poorly understood Methadone for pain significantly contributes Probably multifactorial
– Prescribing to patients at risk • Axis I and Axis II: impulsivity and suicidality• Predisposed to opioid-induced sleep-disordered breathing• Predisposed to methadone-induced QTc prolongation
– Lacking knowledge of drug-specific risks
Deaths with Mention of Methadone by Intent 1999-2003
Deaths with Mention of Methadone by Intent 1999-2003
Minino AM, et al. Deaths: Injuries, 2002. NVSR 54:10. NCHS. 2006. Accessed April 19, 2007 at:http://www.cdc.gov/nchs/data/nvsr/nvsr54/nvsr54_10.pdf.Anderson RN, et al. Deaths: Injuries, 2001. NVSR 52:21. NCHS. 2004. Accessed April 19, 2007 at:http://www.cdc.gov/nchs/data/nvsr/nvsr52/nvsr52_21acc.pdf . Accessed April 19, 2007.
*Includes intent categories homicide and legal intervention
0
500
1,000
1,500
2,000
2,500
3,000
3,500
1999 2000 2001 2002 2003
Year
Met
ha
do
ne
Men
tio
ns
All injury* Unintentional Suicide Undetermined
Opioid-Induced Sleep Disordered BreathingOpioid-Induced Sleep Disordered Breathing
Events per Hour
Per
cen
t o
f P
atie
nts
*
*Bars indicate hi/lo of 95% CI; AHI = apnea-hypopnea index; CAI = central apnea index; OMAI = obstructive and mixed apnea index
Webster LR, et al. Pain Med, 2009
0
10
20
30
40
50
60
70
80
90
AHI > 5AHI > 15AHI > 30CAI > 5CAI > 15
CAI > 30OMAI > 5OMAI > 15OMAI > 30
Obstructive sleep apnea
Central sleep apneaBoth central and obstructive sleep apnea
Sleep apnea: type indeterminate
n = 140
Formulations and RiskFormulations and Risk
Risk of abuse may vary with drug and formulation– Higher concern: Short-acting drugs, including the
rapid onset fentanyl drugs for breakthrough pain– Higher concern: Higher street value drugs, e.g.
oxycodone, hydromorphone– Lower concern: Transdermal fentanyl and
methadone
Formulations and RiskFormulations and Risk
Emergence of abuse deterrent formulations– May reduce unintentional overdose during
recreational or impulsive use– May reduce diversion if less attractive to
those with addiction– Benefits not yet demonstrated and will be
difficult to track
Formulations and RiskFormulations and Risk
Mechanical abuse deterrent formulations– Oxycontin ™ and Remoxy™
• Deters dose dumping: as gelatin capsule dissolves, SR oxycodone released via GI tract
• Difficult to crush, break, dissolve• Cannot inject or snort
Formulations and RiskFormulations and Risk
Chemical abuse deterrent formulations– EMBEDA™
ConclusionConclusion
Despite lack of consensus, there is growing use of opioid therapy for chronic pain– Some is good
– Some does harm
Reducing harm requires education and balanced policies based on best practice approaches