Pain Management and Addiction Medicine Russell K. Portenoy, MD Chairman, Department of Pain 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



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

44

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


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

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


Many RCTs and systematic reviews yield mixed findings and provide little help in developing evidence-based therapy



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



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



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



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



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





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

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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.

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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



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

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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

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1999 2000 2001 2002 2003

Year

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Opioid-Induced Sleep Disordered BreathingOpioid-Induced Sleep Disordered Breathing

Events per Hour

Per

cen

t o

f P

atie

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*

*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


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


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


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

Pain Management and Addiction Medicine Russell K. Portenoy, MD Chairman, Department of Pain Medicine...

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