Addressing the Barriers to Effective Pain Management and

Issues of Opioid Misuse and Abuse

Sponsored by The France FoundationSupported by an educational grant from King Pharmaceuticals

Earl Quijada, MDAssistant Professor, Physical Medicine and Rehab

Linda Loma UniversityLinda Loma, California

Faculty DisclosureIt is the policy of The France Foundation to ensure balance, independence, objectivity, and scientific rigor in all its sponsored educational activities. All faculty, activity planners, content reviewers, and staff participating in this activity will disclose to the participants any significant financial interest or other relationship with manufacturer(s) of any commercial product(s)/device(s) and/or provider(s) of commercial services included in this educational activity. The intent of this disclosure is not to prevent a person with a relevant financial or other relationship from participating in the activity, but rather to provide participants with information on which they can base their own judgments. The France Foundation has identified and resolved any and all conflicts of interest prior to the release of this activity.

The following faculty have indicated they have no relationships with industry to disclose relative to the content of this CME activity:• Dr. Earl Quijada has nothing to disclose.

• Identify the negative impact of persistent pain on health and quality of life, methods to assess pain levels, appropriate use of opioid medications, and documentation required for compliance with regulatory policies

• Integrate appropriate risk assessment strategies for patient abuse, misuse, and diversion of opioids into an overall management approach for acute and chronic pain

• Describe the specific elements of new abuse deterrent technologies associated with opioid therapy, and assess their implications for clinical practice

Educational Learning Objectives

Prevalence of Recurrent and Persistent Pain in the US

• 1 in 4 Americans suffer from recurrent pain (day-long bout of pain/month)

• 1 in 10 Americans report having persistent pain of at least one year’s duration

• 1 in 5 individuals over the age of 65 report pain persisting for more than 24 hours in the preceding month

– 6 in 10 report pain persisting > 1 year

• 2 out of 3 US armed forces veterans report having persistent pain attributable to military service

– 1 in 10 take prescription medicine to manage pain

American Pain Foundation. http://www.painfoundation.org. Accessed March 2010.

A. Nociceptive

B. Inflammatory

C. Neuropathic

D. Noninflammatory/ Nonneuropathic

Noxious Peripheral

Stimuli

Peripheral Nerve Damage

No Known Tissue or Nerve DamageAbnormal Central Processing

Multiple Mechanisms

Inflammation

Multiple Types of Pain

Adapted from Woolf CJ. Ann Intern Med. 2004;140:441-451.1. Chong MS, Bajwa ZH. J Pain Symptom Manage. 2003;25:S4-S11.

• Patients may experience multiple pain states simultaneously1

Examples

• Strains and sprains

• Bone fractures

• Postoperative

• Osteoarthritis

• Rheumatoid arthritis

• Tendonitis

• Diabetic peripheral neuropathy

• Post-herpetic neuralgia

• HIV-related polyneuropathy

• Fibromyalgia

• Irritable bowel syndrome

Sustainedcurrents

PeripheralNociceptive

Fibers

Transient Activation

ACUTEPAIN

Woolf CJ, et al. Ann Intern Med. 2004;140:441-451; Petersen-Felix S, et al. Swiss Med Weekly. 2002;132:273-278; Woolf CJ. Nature.1983;306:686-688; Woolf CJ, et al. Nature. 1992;355:75-78.

Surgeryor

injurycauses

inflammation

Long-Term Consequences of Acute Pain: Potential for Progression to Chronic Pain

SustainedActivation

PeripheralNociceptive

Fibers

Sensitization

CHRONIC PAIN

CNSNeuroplasticity

Hyperactivity

Structural Remodeling

Neuroplasticity in Pain Processing

1.Woolf CJ, Salter MW. Science. 2000;288:1765-1768. 2.Basbaum AI, Jessell TM. The perception of pain. In: Kandel ER, Schwartz JH, et al. eds. Principles of Neural

Science. 4th ed. New York, NY: McGraw-Hill; 2000:479.3.Cervero F, Laird JMA. Pain. 1996;68:13-23.

Stimulus Intensity

100

Injury Normal ResponseTo Painful Stimulus

Allodynia

pain resulting from normally painless stimuli

Hyperalgesia3

heightened sense of pain to noxious stimuli

80

60

40

20

0innocuous noxious

Pa

in S

ens

ati

on

Vicious Cycle of Uncontrolled Pain

Pain

Altered Functional

Status

Decreased Mobility

AvoidanceBehaviors

Social Limitations Diminished

Self-Efficacy

1. Gottschalk A, Smith DS. Am Fam Physician. 2001;63:1979-1984; 2. Iyengar S, et al. J Pharmacol Exp Ther. 2004;311:576-584; 3. Morgan V, et al. Gut. 2005;54:601-607; 4. Reimann W, et al. Anesth Analg. 1999;88:141-145. Vanegas H, Schaible HG. Prog Neurobiol. 2001;64:327-363; 6. Malmberg AB, Yaksh TL. J Pharmacol Exp Ther. 1992;263:136-146; 7. Stein C, et al. J Pharmacol Exp Ther. 1989;248:1269-1275.

Breaking the Chain of Pain Transmission

5-HT = serotonin; NE = norepinephrine; TCA = tricyclic antidepressant

Fine PG, et al. J Support Oncol. 2004;2(suppl 4):5-22. Portenoy RK, et al. In: Lowinson JH, et al, eds. Substance Abuse: A Comprehensive Textbook. 4th ed. Philadelphia, PA: Lippincott, Williams & Wilkins; 2005:863-903.

Multimodal Treatment

Lifestyle ChangeExercise, weight loss

Strategies for Pain and

Associated Disability

PharmacotherapyOpioids, nonopioids, adjuvant analgesics

Interventional Approaches

Injections, neurostimulation

Physical Medicine and Rehabilitation

Assistive devices, electrotherapy

Psychological Support

Psychotherapy, group support

Complementary and Alternative

MedicineMassage, supplements

Components of Chronic Pain

• Chronic pain– Baseline persistent pain– Breakthrough pain (BTP)

• Each component of chronic pain needs to be independently assessed and managed

Portenoy RK, et al. Pain. 1999;81:129-134; Svendsen K, et al. Eur J Pain. 2005;9:195-206.

0

2

4

6

8

10

6 A

M 7 8 9 10

11

12

PM 1 2 3 4 5

6 P

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11

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Time, h

Baseline Pain

BTP

Positioning Opioid Therapyfor Chronic Pain

• Chronic non-cancer pain: evolving perspective– Consider for all patients with severe chronic pain, but

weigh the influences What is conventional practice?

Are there reasonable alternatives?

What is the risk of adverse events?

Is the patient likely to be a responsible drug-taker?

Fine PG, Portenoy RK. Clinical Guide to Opioid Analgesia, 2nd edition, 2007.Jovey RD, et al. Pain Res Manag. 2003;8(Suppl A):3A-28A.Eisenberg E, et al. JAMA. 2005;293:3043-3052.Gilron I, et al. N Engl J Med. 2005;352:1324-1334.

Chronic Opioid Therapy Guidelines and Treatment Principles

Patient Selection

Patient Selection and Risk Stratification (1.1-1.3)

Initial Patient Assessment

Informed Consent and Opioid Management Plans (2.1-2.2)

High-Risk Patients (6.1-6.2)

Alternatives to Opioid Therapy

Use of Psycho-therapeutic

Cointerventions (9.1)

Comprehensive Pain Management Plan

Driving and Work Safety (10.1)

Identifying a Medical Home* and When to Obtain Consultation (11.1-11.2)

Chou R, et al. J Pain. 2009;10:113-130. *Clinician accepting primary responsibility for a patient’s overall medical care.

Chronic Opioid Therapy Guidelines and Treatment Principles (cont)

Trial of Opioid Therapy

Initiation and Titration of Chronic Opioid Therapy (3.1-3.2)

Methadone (4.1)

Opioids and Pregnancy (13.1)

Patient Reassessment

Monitoring (5.1-5.3)

Dose Escalations, High-Dose Opioid Therapy, Opioid Rotation, Indications for Discontinuation of Therapy (7.1-7.4)

Opioid Policies (14.1)

Implement Exit Strategy

Opioid-Related Adverse Effects (8.1)

Continue Opioid Therapy

Monitoring (5.1-5.3)

Breakthrough Pain (12.1)Chou R, et al. J Pain. 2009;10:113-130. *Clinician accepting primary responsibility for a patient’s overall medical care.

Opioid Formulations

Type of Drug Examples

Pure -opioid receptor agonists Morphine, hydromorphone, fentanyl, oxycodone

Dual mechanism opioids Tramadol, tapentadol

Rapid onset (transmucosal) Fentanyl, alfentanil, sufentanil, diamorphine

Immediate release Tramadol, oxycodone

Modified release (long acting) Morphine, methadone, oxycodone

Available with co-analgesic Oxycodone, tramadol, codeine

Only available with co-analgesic Hydrocodone

Formulation Points to Consider

• Dose-limiting issues and toxicity with co-analgesics– 4 g/day acetaminophen limit

• Importance of titration– Risk of overdose, challenges of dose conversion during rotation

• Pharmacokinetics versus temporal patterns of pain• Adherence• Cost• Convenience• Caregiving issues

Domains for Pain Management Outcome: The 4 A’s

• Analgesia

• Activities of Daily Living

• Adverse Events

• Aberrant Drug-Taking Behaviors

Passik SD, Weinreb HJ. Adv Ther. 2000;17:70-83.Passik SD, et al. Clin Ther. 2004;26:552-561.

Model Policy for the Use of Controlled Substances for the Treatment of Pain

Federation of State Medical Boards House of Delegates, May 2004. http://fsmb.org. Accessed March 2010.

Federation of State Medical Boardsof the United States, Inc

FSMB Model PolicyBasic Tenets

• Pain management is important and integral to the practice of medicine

• Use of opioids may be necessary for pain relief• Use of opioids for other than a legitimate medical purpose

poses a threat to the individual and society• Physicians have a responsibility to minimize the potential for

abuse and diversion• Physicians may deviate from the recommended treatment

steps based on good cause• Not meant to constrain or dictate medical decision-making

FSMB, Federation of State Medical Boards

New Illicit Drug Use United States, 2006

PCP†Pain Relievers*

Tranquilizers

Cocaine

Ecstasy LSD†

Marijuana

Inhalants

Stimulants Sedatives Heroin

6991264267

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Substance Abuse and Mental Health Services Administration, Office of Applied Studies. 2006 National Survey on Drug Use and Health. Department of Health and Human Services Publication No. SMA 07-4293; 2007.

*533,000 new nonmedical users of oxycodone aged ≥ 12 years. Past year initiates for specific illicit drugs among people aged ≥ 12 years.†LSD, lysergic acid diethylamide; PCP, phencyclidine.

Definition of Terms

Katz NP, et al. Clin J Pain. 2007;23:648-660.

Misuse• Use of a medication (for a medical purpose) other than as directed or as

indicated, whether willful or unintentional, and whether harm results or not

Abuse• Any use of an illegal drug• The intentional self administration of a medication for a nonmedical

purpose such as altering one’s state of consciousness, eg, getting high

Diversion• The intentional removal of a medication from legitimate and dispensing

channels

Addiction

• A primary, chronic, neurobiological disease, with genetic, psychosocial, and environmental factors influencing its development and manifestations

• Behavioral characteristics include one or more of the following: impaired control over drug use, compulsive use, continued use despite harm, craving

Pseudoaddiction

• Syndrome of abnormal behavior resulting from undertreatment of pain that is misidentified by the clinician as inappropriate drug-seeking behavior

• Behavior ceases when adequate pain relief is provided• Not a diagnosis; rather, a description of the clinical intention

Webster LR, Webster RM. Pain Med. 2005;6(6):432-442.

Prevalence of Misuse, Abuse, and Addiction

Misuse 40%

Abuse: 20%

Total PainPopulationAddiction: 2% to 5%

Medical Use• Pain patients

seeking more pain relief

• Pain patients escaping emotional pain

Who Misuses/Abuses Opioids and Why?

Nonmedical Use

• Recreational abusers

• Patients with disease of addiction

Rx Opioid Users Are Heterogeneous

“Addicted”

(SUD)

“Substance

abusers”

“Recreational

users”“Adherent”

“Chemical copers”

“Addicted”

(SUD)

“Substance abusers”

Nonmedical Users Pain Patients

“Self-Treaters”

Passik SD, Kirsch KL. Exp Clin Psychopharmacol. 2008;16(5):400-404.

Katz NP, et al. Clin J Pain. 2007;23:103-118; Manchikanti L, et al. J Opioid Manag. 2007;3:89-100. Webster LR, Webster RM. Pain Med. 2005;6:432-442.

• Age ≤ 45 years

• Gender

• Family history of prescription drug or alcohol abuse

• Cigarette smoking

• Substance use disorder

• Preadolescent sexual abuse (in women)

• Major psychiatric disorder (eg, personality disorder, anxiety or depressive disorder, bipolar disorder)

• Prior legal problems

• History of motor vehicle accidents

• Poor family support

• Involvement in a problematic subculture

Biological Psychiatric Social

Risk Factors for Aberrant Behaviors/Harm

• 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

Stratify Risk

Webster LR, Webster RM. Pain Med. 2005;6:432-442.

10 Principles of Universal Precautions

1. Diagnosis with appropriate differential

2. Psychological assessment including risk of addictive disorders

3. Informed consent (verbal or written/signed)

4. Treatment agreement (verbal or written/signed)

5. Pre-/post-intervention assessment of pain level and function

6. Appropriate trial of opioid therapy adjunctive medication

7. Reassessment of pain score and level of function

8. Regularly assess the “Four A’s” of pain medicine: Analgesia, Activity, Adverse Reactions, and Aberrant Behavior

9. Periodically review pain and comorbidity diagnoses, including addictive disorders

10.Documentation

Gourlay DL, Heit HA. Pain Med. 2009;10 Suppl 2:S115-123. Gourlay DL, et al. Pain Med. 2005;6(2):107-112.

Initial Visits

• Initial comprehensive evaluation• Risk assessment• Prescription monitoring assessment• Urine drug test• Opioid treatment agreement• Opioid consent form• Patient education

McGill Short Form Pain Questionnaire

Results of Short and Long Form tests correlate well for postsurgical pain

r = 0.67 - 0.86, P 0.002

Melzack R. Pain. 1987;30:191-197.

Principles of Responsible Opioid Prescribing

• Patient Evaluation– Pain assessment and history – Directed physical exam– Review of diagnostic studies– Analgesic and other medication history– Personal history of illicit drug use or substance abuse– Personal history of psychiatric issues– Family history of substance abuse/psychiatric

problems– Assessment of comorbidities– Accurate record keeping

Fine PG, Portenoy RK. Clinical Guide to Opioid Analgesia, 2nd edition, 2007.

Principles of Responsible Opioid Prescribing

Treatment Plan

• I have resolved key points before initiating opioid therapy– Diagnosis established and opioid treatment plan developed

– Established level of risk

– I can treat this patient alone/I need to enlist other consultants to co-manage this patient (pain or addiction specialists)

• I have considered nonopioid modalities– Pain rehabilitation program

– Behavioral strategies

– Non-invasive and interventional techniques

Principles of Responsible Opioid Prescribing

Treatment Plan (cont)

• Drug selection, route of administration, dosing/dose titration• Managing adverse effects of opioid therapy• Assessing outcomes• Written agreements in place outlining patient

expectations/responsibilities • Consultation as needed• Periodic review of treatment efficacy, side effects,

aberrant drug-taking behaviors

Algorithm for theManagement of Chronic Pain

Marcus DA. Am Fam Physician. 2000;61(5):1331-1338.

TCA = tricyclic antidepressants: SSRI = selective serotonin reuptake inhibitors

Pain frequency

Frequency flares of constant disturbing painInfrequent flares < 4 days per week

Analgesics Physical therapy Psychology Additional features

PsychologyPhysical therapy Occupational therapy

Ineffective or require excessive doses

Flare management: oscillatory movements, distraction techniques, trigger point massage

Relaxation Stress management

Short-acting opioids

Neuropathic pain, burning quality, nerve injury, neuralgia

Structural pathology with disability and or overuse of analgesics

Reconditioning Stretching exercises

Body mechanics Work simplification Pacing skills

Cognitive restructuring Relaxation Stress management

First line Adjunctive

Long-acting opioids

Capsaicin cream Mexiletine Long-acting opioids

Antidepressants: TCA, SSRI Antiepileptics: gabapentin, lamotrigine

Medical Records

• Maintain accurate, complete, and current records– Medical Hx & PE– Diagnostic, therapeutic, lab results– Evaluations/consultations– Treatment objectives– Discussion of risks/benefits– Tx and medications– Instructions/agreements– Periodic reviews– Discussions with and about patients

Fishman SM. Pain Med. 2006;7:360-362. Federation of State Medical Boards of the United States, Inc. Model Policy for the Use of Controlled Substances for the Treatment of Pain. 2004.

Considerations

• What is conventional practice for this type of pain or pain patient?• Is there an alternative therapy that is likely to have an equivalent or

better therapeutic index for pain control, functional restoration, and improvement in quality of life?

• Does the patient have medical problems that may increase the risk of opioid-related adverse effects?

• Is the patient likely to manage the opioid therapy responsibly?• Who can I treat without help?• Who would I be able to treat with the assistance of a specialist?• Who should I not treat, but rather refer, if opioid therapy is a

consideration?

Fine PG, Portenoy RK. Clinical Guide to Opioid Analgesia. Vendome Group, New York, 2007.

Marcus DA. Am Fam Physician. 2000;61(5):1331-1338.

Initiation of Therapy for

Chronic Pain

Monitoring Chronic Pain

Review of Efficacy of Therapy

Marcus DA. Am Fam Physician. 2000;61(5):1331-1338.

Opioid Treatment Agreement

http://www.lni.wa.gov/ClaimsIns/Files/OMD/agreement.pdf. Accessed March 2010.

Differential Diagnosis of Aberrant Drug-Taking Attitudes and Behavior

• Addiction (out-of-control, compulsive drug use)• Pseudoaddiction (inadequate analgesia)• Other psychiatric diagnosis

– Organic mental syndrome (confused, stereotyped drug-taking)

– Personality disorder (impulsive, entitled, chemical-coping behavior)

– Chemical coping (drug overly central)– Depression/anxiety/situational stressors

(self-medication)

• Criminal intent (diversion)

Passik SD, Kirsh KL. Curr Pain Headache Rep. 2004;8:289-294.

Identifying Who Is at Risk for Opioid Abuse and Diversion

• Predictive tools • Aberrant behaviors• Urine drug testing• Prescription monitoring

programs• Severity and duration of pain• Pharmacist communication• Family and friends• Patients

Signs of Potential Abuse and Diversion

• Request appointment toward end-of-office hours• Arrive without appointment• Telephone/arrive after office hours when staff are anxious

to leave• Reluctant to have thorough physical exam, diagnostic

tests, or referrals• Fail to keep appointments• Unwilling to provide past medical records or names of

HCPs• Unusual stories

However, emergencies happen: not every person in a hurry is an abuser/diverter

Drug Enforcement Administration. Don't be Scammed by a Drug Abuser. 1999. Cole BE. Fam Pract Manage. 2001;8:37-41.

Risk Assessment Tools

• Addiction Behaviors Checklist (ABC) – Evaluate and monitor behaviors indicative of

addiction related to prescription opioids in patients

with chronic pain

• Addiction Severity Index (ASI)– Assess current and lifetime substance-use

problems and prior treatment

• Current Opioid Misuse Measure (COMM)– Periodically monitor aberrant medication-related

behaviors in patients with chronic pain currently on

opioid therapy

Passik SD, Squire P. Pain Med. 2009;10 Suppl 2:S101-14.

Risk Assessment Tools (cont)

• Drug Abuse Screening Test (DAST-10)– Screen for probably drug abuse or dependence

• Pain Medication Questionnaire (PMQ)– Assess risk for opioid medication misuse in patients with

chronic pain

• Screening Instrument for Substance Abuse Potential (SISAP)

– Identify individuals with possible substance-abuse history

• Opioid Risk Tool (ORT)– Predict which patients might develop aberrant behavior when

prescribed opioids for chronic pain

Passik SD, Squire P. Pain Med. 2009;10 Suppl 2:S101-14.

Risk Assessment Tools (cont)

• Diagnosis, Intractability, Risk, Efficacy (DIRE)– Predict the analgesic efficacy of, and patient compliance to,

long-term opioid treatment in the primary care setting

• Screener and Opioid Assessment for Patients with Pain-Revised (SOAPP-R)

– Predict aberrant medication-related behaviors in patients with chronic pain considered for long-term opioid therapy

» Empirically-derived, 24-item self-report questionnaire

» Reliable and valid

» Less susceptible to overt deception than past version

» Scoring: 18 identifies 90% of high-risk patients

Passik SD, Squire P. Pain Med. 2009;10 Suppl 2:S101-14. Butler SF, et al. J Pain. 2008;9:360-372.

Mark each box that applies Female Male

1. Family history of substance abuse

– Alcohol

– Illegal drugs

– Prescription drugs

1

2

4

3

3

4

2. Personal history of substance abuse

– Alcohol

– Illegal drugs

– Prescription drugs

3

4

5

3

4

5

3. Age (mark box if 16-45 years) 1 1

4. History of preadolescent sexual abuse 3 0

5. Psychological disease

– ADD, OCD, bipolar, schizophrenia

– Depression

2

1

2

1

ORT Validation

• Exhibits high degree of sensitivity and specificity

• 94% of low-risk patients did not display an aberrant behavior

• 91% of high-risk patients did display an aberrant behavior

N = 185ADD, attention deficit disorder; OCD, obsessive-compulsive disorder.Webster LR, Webster RM. Pain Med. 2005;6:432-442.

SOAPP

Mr. Jackson’s Score = 3

To score the SOAPP, add ratings of all questions.

A score of 4 or higher is considered positive

Sum of Questions

SOAPP Indication

4 +

< 4 -

Name:_________________ Date:___________

The following survey is given to all patients who are on or being considered for opioids for their pain. Please answer each question as honestly as possible. This information is for our records and will remain confidential. Your answers will not determine your treatment. Thank you.

Please answer the questions below using the following scale:

0 = Never, 1 = Seldom, 2 = Sometimes, 3 = Often, 4 = Very Often

1. How often do you have mood swings?

2. How often do you smoke a cigarette within an hour after you wake up?

3. How often have you taken medication other than the way that it was prescribed?

4. How often have you used illegal drugs (for example, marijuana, cocaine, etc.) in the past five years?

5. How often in your lifetime have you had legal problems or been arrested?

Please include any additional information you wish about the above answers. Thank you

0 1 2 3 4

0 1 2 3 4

0 1 2 3 4

0 1 2 3 4

0 1 2 3 4

Chris Jackson 9/16/09

О

О

Risk Assessment Tools Highlights

• ORT, SOAPP & DIRE– Best assess abuse potential among those being

considered for long-term opioid therapy

• COMM & PMQ– Characterize degree of medication misuse or

aberrant behavior once opioids are started

• DAST-10 & PMQ– More suitable for assessing current alcohol and/or

drug abuse than potential for such abuse

Passik SD, et al. Pain Med. 2008;10 Suppl 2:S145-166.

Urine Drug Testing

• When to test?– Randomly, annually, PRN

• What type of testing?– POC, GS/MS

• How to interpret– Metabolism of opioids– False positive and negative results

• What to do about the results– Consult, refer, change therapy, discharge

The Role of UDT

• UDT in clinical practice may– Provide objective documentation of

compliance with treatment plan by detecting presence of a particular drug or its metabolites

– Assist in recognition of addiction or drug misuse if results abnormal

• Results are only as reliable as testing laboratory’s ability to detect substance in question

Heit HA, Gourlay DL. J Pain Symptom Manage. 2004;27:260-267.Dove B, Webster LR. Avoiding Opioid Abuse while Managing Pain: a Guide for Practitioners. North Branch, MN: Sunrise River Press; 2007.

• Positive forensic testing– Legally prescribed

medications– Over-the-counter

medications– Illicit drugs or unprescribed

medications– Substances that produce

the same metabolite as that of a prescribed or illegal substance

– Errors in laboratory analysis

• Negative compliance testing– Medication bingeing– Diversion– Insufficient test sensitivity– Failure of laboratory to test for

desired substances

Heit HA, Gourlay DL. J Pain Symptom Manage. 2004;27:260-267.

Positive and Negative Urine Toxicology Results

Urine Drug Testing

• Initial testing done with class-specific immunoassay drug panels– Typically do not identify individual drugs within a class

Heit HA, Gourlay D. J Pain Sympt Manage. 2004:27:260-267.

• Followed by a technique such as GC/MS– To identify or confirm the

presence or absence of a specific drug and/or its metabolites

UDT Immunoassay Screening

• Lab Testing or POCT– Drug class– High sensitivity,

low specificity– Rapid results– Not quantitative

POCT, point-of-care testing

Hammett-Stabler CA, Webster LR. A Clinical Guide to Urine Drug Testing. Stamford, CT: PharmaCom Group Inc; 2008.

Detection of Opioids

• Opiate immunoassays detect morphine and codeine– Do not detect synthetic opioids

Methadone Fentanyl

– Do not reliably detect semisynthetic opioids Oxycodone Hydrocodone Buprenorphine Hydromorphone

• GC/MS will identify these medications

Heit HA, Gourlay D. J Pain Sympt Manage. 2004:27:260-267.

UDT Laboratory-Based Tests

• GC/MS, LC/ MS, ELISA– High sensitivity,

high specificity– Expensive– Quantitative– 1-3 days for

results

ELISA, enzyme-linked immunosorbent assay; GC, gas chromatography; LC, liquid chromatography; MS, mass spectrometry.

Hammett-Stabler CA, Webster LR. A Clinical Guide to Urine Drug Testing. Stamford, CT: PharmaCom Group Inc; 2008.

RESULTS OF CONTROLLED SUBSTANCE UDT: WORKPLACE

Donor Name: Jack Donor ID #: 1897221 Specimen ID #: 1897221-112

Accession #: None assigned Reason for test: RandomDate collected: 04/11/2008 Time collected: 1648Date received: 04/15/2008 Date reported: 04/15/2008

Class or Analyte Result Screen Cut-OffAMPHETAMINES NEGATIVE 1,000 ng/mlBARBITUATES NEGATIVE 200 ng/mlBENZODIAZEPINES NEGATIVE 200 ng/mlCANNABINOIDS NEGATIVE 50 ng/mlCOCAINE NEGATIVE 300 ng/mlMETHADONE NEGATIVE 150 ng/mlOPIATES POSITIVE 100 ng/ml

Validity Test Result Normal RangeCREATININE NORMAL at 33.4 mg/dL ≥ 20 mg/dLSPECIFIC GRAVITY NORMAL ≥ 1.003pH NORMAL 4.6-8.0

Dihydromorphone

Opioid Metabolism

Dihydrocodeine

Minor Minor

Gourlay D, et al. http://www.familydocs.org/assets/171_UDT%202006.pdf. Accessed March 2010;Cone EJ, et al. J Anal Toxicol. 2006;30:1-5; Heit HA, Gourlay D. Personal Communication. 2008.

Not comprehensive pathways, but may explain presence

of apparently unprescribed drugs

Detection Times of Common Drugs of MisuseDrug Approximate Retention Time

Amphetamines • 48 hours

Barbiturates• Short-acting (eg, secobarbital), 24 hours

• Long-acting (eg, phenobarbital), 2–3 weeks

Benzodiazepines• 3 days if therapeutic dose is ingested

• Up to 4–6 weeks after extended dosage (≥ 1 year)

Cannabinoids

• Moderate smoker (4 times/week), 5 days

• Heavy smoker (daily), 10 days

• Retention time for chronic smokers may be 20–28 days

Cocaine • 2–4 days, metabolized

Ethanol • 2–4 hours

Methadone • Approximately 30 days

Opiates • 2 days

Phencyclidine• Approximately 8 days

• Up to 30 days in chronic users (mean value = 14 days)

Propoxyphene • 6–48 hours

Gourlay DL, Heit HA. Pain Med. 2009;10 Suppl 2:S115-123.

Risk Evaluation and Mitigation Strategies

Position of the FDA• The current strategies for intervening with [the problem of

prescription opioid addiction, misuse, abuse, overdose and death] are inadequate

• New authorities granted under FDAAA: [FDA] will now be implementing Risk Evaluation and Mitigation Strategies (REMS) for a number of opioid products

• [FDA expects] all companies marketing these products to [cooperate] to get this done expeditiously

• If not, [FDA] cannot guarantee that these products will remain on the market

Rappaport BA. REMS for Opioid Analgesics: How Did We Get Here? Where are We Going? FDA meeting of manufacturers of ER opioids, FDA White Oak Campus, Silver Spring, MD. March 3, 2009.

States with PMPs

Operational PMP:32 Start-up phase: 6 In legislative process: 11 No action: 1

Office of Diversion Control. http://www.deadiversion.usdoj.gov/faq/rx_monitor.htm#1. Accessed March 2010.

Identifying and Managing Abuse and Diversion

• Assessing risk and aberrant behaviors• Performing scheduled and random UDTs• Utilization of PMPs• Assessing stress and adequacy of pain control• Developing good communication with pharmacists• Receiving input from family, friends, and other patients

Case Study: Opioid Renewal Clinic What is the impact of a structured opioid renewal program?

• Primary goal: reduce oxycodone SA use to 3% of opioids • Setting

– Primary care – Managed by nurse practitioner and clinical pharmacist – Philadelphia VA pain clinic

• Structured program– Electronic referral by PCP

• Signed Opioid Treatment Agreement• UDT

– Support from multidisciplinary pain team: addiction psychiatrist, rheumatologist, orthopedist, neurologist, and physiatrist

– Multimodal management • Opioids • NSAIDs and acetaminophen for osteoarthritis• Transcutaneous electrical stimulation (TENS) units• Antidepressants and anticonvulsants for neuropathic pain• Reconditioning exercises

Wiedemer NL, et al. Pain Med. 2007;8(7):573-584.

Opioid Renewal Clinic: Results

• OTAs increased: 63 214

• Monthly UDTs increased: 80 200

• Oxycodone SA use decreased

– Quarterly costs: $130,000 $5,000

– Percent of opioids: 22.5% 0.4%

• ER visits reduced 73%

• Unscheduled PCP visits reduced 60%

• PCPs satisfied (questionnaire)

• 171/335 patients referred had aberrant drug-taking behaviors

– 45% adhered to OTA (resolved aberrant behaviors)

– 38% self-discharged from ORC

– 13% referred for addiction treatment

– 4% consistently negative UDT

Wiedemer NL, et al. Pain Med. 2007;8(7):573-584.

Pharmacologic • Sequestered antagonist• Bio-available antagonist• Pro-drug

Combination Mechanisms

Physical• Difficult to crush• Difficult to extract

Aversive Component• Capsaicin – burning sensation• Ipecac – emetic• Denatonium – bitter taste

Deterrent Packaging• RFID – Protection• Tamper-proof bottles

Incr

easi

ng

Dir

ect

Ab

use

Det

erre

nce

Opioid Abuse-Deterrent Strategies Hierarchy

Prescription Monitoring

Electronic Track and Trace RFID

• Secures integrity of drug supply chain by providing accurate drug "pedigree" – A record documenting that the drug was manufactured and

distributed under secure conditions. We particularly advocated for the implementation of and noted that radio-frequency identification (RFID) is the most promising

• RFID technology – Tiny radio frequency chip containing essential data in the form of an

electronic product code (EPC) – Each discrete product unit has a unique electronic serial number– Product can be tracked electronically through every step of the

supply chain

RFID, radiofrequency identification

Physical Deterrent: Viscous Gel Base• SR oxycodone formulation: Remoxy™

– Deters dose dumping Accessing entire 12-h dose of CR medication at 1 time

– Difficult to crush, break, freeze, heat, dissolve The viscous gel-cap base of PTI-821 cannot be injected Resists crushing and dissolution in alcohol or water

Aversive Component

• Capsaicin– Burning sensation

• Ipecac – Emetic

• Denatonium– Bitter taste

• Niacin – Flushing, irritation

Pharmacologic Deterrent: Antagonist

• Sequestered antagonist• Bioavailable antagonist• Antagonists are released

only when agent is crushed for extraction– Oral-formulation

sequestered antagonist becomes bioavailable only when sequestering technology is disrupted; targeted to prevent intravenous abuse

Webster LR, Dove B. Avoiding Opioid Abuse While Managing Pain: A Guide for Practitioners. 1st ed. North Branch, MN: Sunrise River Press; 2007.

Remaining Questions

• How much does the barrier approach deter the determined abuser?

• How much do agonist/antagonist compounds retain efficacy?

• How much do agonist/antagonist compounds pose serious adversity?

Patient Case Studies

Case Study 1

• A 56-year-old healthy male with acute back pain

• Conservative therapy ineffective

• Dx with acute thoracic compression fractures

• Persistent pain 6/10 and activity related pain 10/10

• ORT 5

• UDT consistent therapy

• PMP: no opioids

• Rx started with hydrocodone 10 mg/APAP q 4 hours

• Titrated to 50 mg CR morphine/naltrexone BID

• Monitoring– Weekly visits until stable– Prescribe only enough medication until next visit

• RX– Short acting for BTP– CR formulation (with less street attractiveness)– Vertebroplasty partially effective

• Six month follow-up– Much improved; pain 2/10, => tapered of opioids by 70%– No aberrant behaviors– PMP showed no aberrant behavior– Monthly UDT consistent with therapy

Case Study 1 (cont)

Case Study 2

• 38-year-old female actress with ovarian cancer and peripheral neuropathy from therapy

• ORT score was 9• Urine drug test: THC, amphetamines• History of oxycodone addiction, ADD, sexual abuse• Smokes 1 pack per day since the age of 12• Consumes 20 drinks per week• PMP: several opioid prescriptions from different providers

• RX – Instructed to D/C THC– OTA– Pregabalin 600 mg/day– Methadone was slowly titrated to 10 mg qid, Education for Safe Use

• Two weeks later– Patient said she couldn’t tolerate methadone – Asked for oxycodone– Pregabalin is causing confusion and severe memory impairment,

can’t remember her lines in performance

Case Study 2 (cont)

• High risk determines what type of monitoring/therapy– Can oxycodone be safely prescribed?

• Abnormal PMP suggest substance abuse or diversion– UDT and PMP role in monitoring? Frequency?

• What to do about THC?– What if it is medical marijuana?

• Positive UDT amphetamine due to ADD treatment?– Can UDTs differentiate methamphetamine from Adderall?

• What multi-therapeutic approaches should be taken?• Should opioids be prescribed?

Case Study 2 (cont)

Conclusion

• Use of opioids may be necessary for pain relief• Balanced multimodal care

– Use of opioids as part of complete pain care– Anticipation and management of side effects– Judicious use of short and long acting agents– Focus on persistent and breakthrough pain– Maintain standard of care

H&P, F/U, PRN referral, functional outcomes, documentation

• Treatment goals– Improved level of independent function– Increase in activities of daily living– Decreased pain

• Pharmacovigilance– Functional outcomes– Standard medical practice– FSMB policy

• Certain– It is required

• Uncertain– What is meant by pain management?– Who needs what treatment?– Do universal approaches work?– Does it improve outcomes?

For patients For regulators

Conclusion (cont)

Online ResourcesResource Web Address

American Academy of Pain Medicine

http://www.painmed.org/clinical_info/guidelines.html

American Pain Societyhttp://www.ampainsoc.org/pub/cp_guidelines.htm

http://www.ampainsoc.org/links/clinician1.htm

Federation of State Medical Boards

http://www.fsmb.org/RE/PAIN/resource.html

American Academy of Pain Management

http://www.aapainmanage.org/literature/Publications.php

PMQhttp://www.permanente.net/homepage/kaiser/pdf/59761.pdf

McGill Pain Questionnaire (Melzack R. Pain.1987;30:191-197)

Opioid Management Plan http://www.aafp.org/afp/20000301/1331.html

Opioid Treatment Agreement http://www.lni.wa.gov/ClaimsIns/Files/OMD/agreement.pdf.