Opioid Analgesics Risk Evaluation and Mitigation Strategy ...

Opioid AnalgesicsRisk Evaluation and Mitigation Strategy (REMS)

© 2019 Rockpointe

Jointly provided by

This activity is supported by an independent educational grant from the Opioid Analgesic REMS Program Companies. Please see https://ce.opioidanalgesicrems.com/RpcCEUI/rems/pdf/resources/List_of_RPC_Companies.pdf for a listing of REMS Program Companies. This activity is intended to be fully compliant with the Opioid Analgesic REMS education requirements issued by the US Food and Drug Administration.

In collaboration with

Christopher Gharibo, MDAssociate ProfessorDepartments of Anesthesiology and Pain MedicineDepartment of OrthopedicsNYU School of Medicine;Medical Director of Pain MedicineNYU Langone HealthNew York, NY

Aaron Williams, MA Senior Director of Training and TA for Substance UseNational Council for Behavioral HealthWashington, DC

Program FacultyProgram FacultyTimothy J. Atkinson, PharmD, BCPS, CPEClinical Pharmacy Specialist, Pain ManagementDirector, PGY2 Pain Management & Palliative CareVA Tennessee Valley Healthcare SystemNashville, TN

NCBH SpeakerNCBH Speaker

Christopher Gharibo, MDAssociate ProfessorDepartments of Anesthesiology and Pain MedicineDepartment of OrthopedicsNYU School of Medicine;Medical Director of Pain MedicineNYU Langone HealthNew York, NY

Timothy J. Atkinson, PharmD, BCPS, CPEClinical Pharmacy Specialist, Pain ManagementDirector, PGY2 Pain Management & Palliative CareVA Tennessee Valley Healthcare SystemNashville, TN

Steering CommitteeSteering CommitteeCharles E. Argoff, MDProfessor of NeurologyAlbany Medical CollegeDirector, Comprehensive Pain CenterDirector, Pain Management FellowshipAlbany Medical CenterAlbany, NY

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DisclosuresDisclosuresFaculty and Steering Committee Disclosures

The faculty and steering committee reported the following relevant financial relationships that they or their spouse/partner have with commercial interests:

Charles E. Argoff, MD: Speakers’ Bureau: Allergan, Daiichi Sankyo, Teva, Amgen, Novartis, Lilly, Assertio, Tercera; Advisory Board: BioDelivery Sciences, Collegium, Pfizer, Lilly, Regeneron, Scilex, Flowonix, US WorldMeds, Novartis, Teva, Vertex, Kaleo, Shionoghi; Grants/Research Support: Jazz Pharma, Gruenthal, Allergan; Royalty: Elsevier; Stock/Shareholder: Assertio, Pfizer

Timothy J. Atkinson, PharmD, BCPS, CPE: Advisory Board: Daiichi Sankyo, Purdue Pharma; Consultant: Axial Healthcare Inc.

Christopher Gharibo, MD: Advisory Board: Pernix, Daiichi Sankyo, AstraZeneca, Nuven, Kaleo; Speakers’ Bureau: Daiichi Sankyo, AstraZeneca, Nuven, Kaleo

Aaron Williams, MA: Nothing to disclose

Non-faculty DisclosuresNon-faculty content contributors and/or reviewers reported the following relevant financial relationships that they or their spouse/partner have with commercial interests:

Rebecca Jimenez-Sanders, MD: Speaker’s Bureau: Amgen, Teva; Kathy Merlo; Blair St. Amand; Martin Myers, MD; Ashley Marostica RN, MSN, CCM; Brian Jack, MD; USF Health CPD staff: Nothing to disclose

Keypad NumberKeypad Number

• The FDA requires reporting of de-identified findings from this program; however, the provider needs your personal information for accreditation reporting. Your keypad number will be used in place of personal information for the FDA report.

• Your evaluation is stuffed into the syllabus, please take a minute to write in your keypad number at the top of the form

Educational ObjectivesEducational ObjectivesAt the conclusion of this activity, participants should be able to:

• Identify risk factors and vulnerabilities associated with addiction to opioid analgesics and provide patient/caregiver counselling when necessary

• Discuss the components of an effective treatment plan, including patient interactions, treatment goals, and collaboration within the healthcare team

• Analyze the specific benefits and risks to initiating non-medication therapies before utilizing long-term medications

• Recognize patients who are candidates for treatment with nonopioid pharmacologic analgesics

• Explain the decision to initiate long-term opioid analgesics, including ER/LA opioids, with consideration to providing in-home naloxone

• Determine when referral to a pain specialist is appropriate for a patient with chronic pain

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Please rate your confidence in your ability to develop a treatment plan for a patient with chronic pain:

1. Not confident

2. Slightly confident

3. Confident

4. Highly confident

5. Expert

Polling Question 1Polling Question 1

The Prevalence of Chronic Pain in the US Is HighThe Prevalence of Chronic Pain in the US Is High

• Approximately 100 million US adults experience chronic pain (33%)

• Consider appropriate nonpharmacologic, nonopioid options before starting opioids

• If an opioid is chosen consider benefit vs risk

IOM (Institute of Medicine). Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research. 2011; www.painpolicy.wisc.edu.

Ensure availability of opioids

for patients with pain

Establish systems of control

to prevent abuseAND

Adapted

Physical Social

Anger/Fear

Anger/Fear

• Relationships

• Ability to show affection/sexual function

• Isolation

• Function

• Activities of daily living

• Sleep/rest

Chronic Pain Affects Many Dimensions of Patient LifeChronic Pain Affects Many Dimensions of Patient Life

Borneman T, et al. Oncol Nurs Forum. 2003;30(6):997-1005.

Psychological

Anxiety/Depression

Anxiety/Depression

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Chronic Pain Landscape and ChallengesChronic Pain Landscape and Challenges

• Partial efficacy of all therapies

• Bothersome and dangerous adverse event profile

• Lack of potential cure

• Treatment focuses on palliative care, not prevention or coping

• Similar to approach taken with other chronic conditions (e.g. diabetes)

• Overriding goal is to help patients learn how to live with pain and improve quality of life

Barriers to Effective Pain ManagementBarriers to Effective Pain Management

• Political– Attitudes, behaviors, expectations– Prescribing guidelines

• Insurance– Step therapy– Denials

• Legal– Fear of sanctions

• Lack of access to interdisciplinary pain management

Opioid Morbidity and Mortality2017/2016 By the NumbersOpioid Morbidity and Mortality2017/2016 By the Numbers

• 72,300 drug overdose deaths

• 49,000 opioid overdose deaths

• 29,400 fentanyl overdose deaths

• 15,900 heroin overdose deaths

1. National Center for Health Statistics, CDC Wonder. 2. Volkow ND, McLellan AT. N Engl J Med. 2016;374:1253-1263.3. https://www.nytimes.com/interactive/2017/09/02/upshot/fentanyl-drug-overdose-deaths.html.

• 19,300 prescription opioid overdose deaths

• 3,280 methadone overdose deaths

• 52 million non-medical use all drugs

• 2.2 million non-medical use prescription opioids

• 1-8% become addicted

• 4% advance to heroin

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The Need for Comprehensive Pain EducationThe Need for Comprehensive Pain Education• Two competing public health concerns

1. The large number of Americans with acute and chronic pain

2. The epidemic of prescription opioid abuse

• Healthcare providers need to understand1. All options to treat pain – nonpharmacologic, nonopioids

2. Only use opioids when other treatments fail and benefits exceed risks

• With better understanding of treatment options, healthcare providers can counsel patients about options and provide strategies to reduce risk

Definitions and Mechanisms of Pain

Definitions and Mechanisms of Pain

IASP Definition of PainIASP Definition of Pain

“An unpleasant sensory and emotional experience associated

with actual or potential tissue damage, or described in terms of

such damage.”

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SustainedCurrents

PeripheralNociceptive

Fibers

Transient Activation

ACUTEPAIN

Woolf CJ. Ann Intern Med. 2004;140:441-451; Petersen-Felix S, Curatolo M. Swiss Med Weekly. 2002;132:273-278; Woolf CJ, Wall PD. 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 PainLong-Term Consequences of Acute Pain Potential for Progression to Chronic Pain

SustainedActivation

PeripheralNociceptive

Fibers

Sensitization

CHRONIC PAIN

CNSNeuroplasticity

Hyperactivity

Structural Remodeling

Examples of nociceptive pain include which of the following?

1. Irritable bowel syndrome, pelvic pain syndrome, interstitial cystitis

2. Rheumatoid arthritis, gout, neck and back pain with structural pathology

3. Acute herpes zoster, postoperative pain, radiculopathy

4. All of the above


Chronic Pain Conditions Can Be ClassifiedBased on Type of Pain PathophysiologyChronic Pain Conditions Can Be ClassifiedBased on Type of Pain Pathophysiology

Three Main Types of Pain PathophysiologyThree Main Types of Pain Pathophysiology

Nociceptive Neuropathic

Pain without identifiable nerve or tissue damage; thought to result from

persistent neuronal dysregulation, affective system disorder

EXAMPLES:Any pain

Pain without identifiable nerve or tissue damage; thought to result from

persistent neuronal dysregulation, affective system disorder

EXAMPLES:Any pain

Pain related to damage of somaticor visceral tissue, due to trauma

or inflammation

EXAMPLES:rheumatoid arthritis, osteoarthritis, gout

Pain related to damage of somaticor visceral tissue, due to trauma

or inflammation

EXAMPLES:rheumatoid arthritis, osteoarthritis, gout

Pain related to damage ofperipheral or central nerves

EXAMPLES:painful diabetic peripheral

neuropathy (pDPN), postherpetic neuralgia

Pain related to damage ofperipheral or central nerves

EXAMPLES:painful diabetic peripheral

neuropathy (pDPN), postherpetic neuralgia

SensoryHypersensitivity

Phillips K, Clauw DF. Best Pract Res Clin Rheumatol. 2011;25(2):141-154. Adapted from Stanos S, et al. Postgrad Med. 128:502-515.

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The Three Types of Pain, Separately or Together, Give Rise to Various Chronic Pain ConditionsThe Three Types of Pain, Separately or Together, Give Rise to Various Chronic Pain Conditions

Adapted from Stanos S, et al. Postgrad Med. 128:502-515.

SensoryHypersensitivity

• Fibromyalgia• Irritable bowel syndrome• Functional dyspepsia• Interstitial cystitis

• Neck and back pain withoutstructural pathology

• Myofascial pain / Temporo-mandibular joint (TMJ) disorder

• Pelvic pain syndrome• Some headaches• Chronic fatigue syndrome

• Gout• Osteoarthritis• Rheumatoid arthritis• Tendonitis, bursitis• Ankylosing spondylitis• Tumor-related

nociceptive pain• Neck and back pain with structural pathology• Sickle-cell disease• Inflammatory bowel disease

Nociceptive

• Postherpetic neuralgia• Painful diabetic peripheral neuropathy• Sciatica/stenosis• Spinal cord injury pain• Tumor-related neuropathy• Chemotherapy-induced neuropathy• Small-fiber neuropathy• Post-stroke pain• Multiple sclerosis pain• Persistent postoperative pain

Neuropathic

Chronic low back painhas been acknowledged to have multiple potential mechanisms and is often viewed as a prototypical “mixed-pain state”

Which Person Has Pain?Which Person Has Pain?

Acute Postoperative Pain Has Been Associated With Chronic Pain After Common ProceduresAcute Postoperative Pain Has Been Associated With Chronic Pain After Common Procedures

Procedure Incidence of ChronicPostsurgical Pain

US Surgical Volumes(1000s)1

Amputation 57-62%2 159

Breast surgery 27-48%3,4 479

Thoracotomy 52-61%5,6 Unknown

Inguinal hernia repair 19-40%7,8 609

Coronary artery bypass 23-39%9-11 598

Caesarean section 12%12 220

1. Kehlet et al. Lancet. 2006;367:1618-1625; 2. Hanley et al. J Pain. 2007;8:102-10; 3. Carpenter et al. Cancer Prac. 1999;7:66-70; 4. Poleschuk et al. J Pain. 2006;7:626-634; 5. Katz et al. Clin J Pain. 1996;12:50-55; 6. Perttunen et al. Acta Anaesthesiol Scand. 1999;43:563-567; 7.Massaron et al. Hernia. 2007;11:517-525; 8. O’Dwyer et al. Br J Surg. 2005;92:166-170; 9. Steegers et al. J Pain. 2007;8:667-673; 10. Taillefer et al. J Thorac Cardiovasc Surg. 2006;131:1274-1280; 11. Bruce et al. Pain. 2003;104:265-273; 12. Nikolajsen et al. Acta Anaesthesiol Scand. 2004;48:111-116.

Factors correlated with the development of postsurgical chronic pain1:

1. Nerve injury2. Inflammation3. Intense acute

postoperative pain

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Bio-Psycho-Social ModelBio-Psycho-Social Model

Of all approaches to the treatment of pain, none has a stronger evidence basis for efficacy, cost-effectiveness than

interdisciplinary care

Establishing Pain Relief GoalsEstablishing Pain Relief Goals

• Goals for pain management should be specific, measurable, and patient-centered

• Goals focused solely on numeric pain ratings can be problematic• Clinical trials suggest that a 33% to 50% decrease in pain intensity

is meaningful • Goal setting

– Collaborative, focus on functional improvement• Be realistic

– Eliminating pain is often not realistic

http://prc.coh.org/pdf/Goals-FF%205-10.pdf.

Access to Interdisciplinary CareAccess to Interdisciplinary CareNation

No. Citizens / Clinic

Change in No. Clinics in Past Decade

Australia 255,555Belgium 1,222,222 Canada 172,413 Denmark 560,000 England and Wales 405,797 France 802,469 Israel 727,000 Netherlands 2,438,571 New Zealand 440,000 Spain 7,666,666 Sweden 339,285 United States (non-VHA*) 3,244,444 United States (VHA*) 369,491

Study results showed that a precipitous decrease in the number of interdisciplinary programs occurred in U.S. between 1999 and 2012, except among the Veteran’s Health Administration. During this same time period, the number of interdisciplinary programs in industrialized nations with National Health Services increased dramatically.

Study results showed that a precipitous decrease in the number of interdisciplinary programs occurred in U.S. between 1999 and 2012, except among the Veteran’s Health Administration. During this same time period, the number of interdisciplinary programs in industrialized nations with National Health Services increased dramatically.

Schatman ME. J Pain Res. 2015;8:885-887.

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Assessing Patients in Pain Assessing Patients in Pain

When assessing patients in pain, the main focus should be on:

1. Eliminating side effects of pain medications

2. Reducing dosages of pain medications

3. Restoring the patient’s functional status

4. Looking for signs of medication misuse/abuse/diversion


Pain AssessmentPain Assessment• Self report is the most reliable or unreliable measure of pain intensity

as there are no biological markers of pain

• Simply worded questions and tools, which can be easily understood, are the most effective

• Most widely used pain intensity scales:– Numeric Rating Scale (NRS)– Verbal Descriptor Scale (VDS)– Faces Pain Scale-Revised (FPS-R)

• We must treat the patient, not a number!• Focus is on functional restoration

Flaherty E. Try This: Best Practices in Nursing Care to Older Adults. 2007;7.

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Elements of a Comprehensive AssessmentUse Appropriate ToolsElements of a Comprehensive AssessmentUse Appropriate Tools

• History/physical examination/ diagnostic testing

• Be aware of risk of acute pain transitioning to chronic pain

• Psychosocial evaluation• Risk identification

– State prescription monitoring programs

• Special populations: pediatric, elderly, pregnancy

• State medical boards may have specific regulations, e.g., Medical Board of California:– History/Physical Examination

• “A medical history and physical examination must be accomplished. This includes an assessment of the pain, physical and psychological function; a substance abuse history; history of prior pain treatment; an assessment of underlying or coexisting diseases or conditions; and documentation of the presence of a recognized medical indication for the use of a controlled substance.”

Seek objective confirmatory data

Order diagnostic tests (appropriate to complaint)

General: vital signs, appearance, posture, gait, & pain behaviors

Neurologic exam

Musculoskeletal Exam• Inspection

• Palpation• Percussion• Auscultation

• Provocative maneuvers

Cutaneous or trophic findings

Components of patient evaluation for pain

Lalani I, Argoff CE. History and Physical Examination of the Pain Patient. In: Raj's Practical Management of Pain. 4th ed. 2008;177-88. Chou R, et al. J Pain. 2009;10:113-30.

Perform Thorough Evaluation and Assessment of PainPerform Thorough Evaluation and Assessment of Pain

Pain DescriptorsPain DescriptorsTen Components Questions to Ask

1. History of onset How/when did your pain begin? What was the last time you were pain free?

2. Location Where exactly is your pain?

3. Quality What does it feel like (e.g., sharp, dull, burning, cramping)?

4. IntensityHow would you rate your pain now? When is pain the least? At the worst? On average? Use an intensity scale appropriate to patient’s language, development and cognitive level.

5. Temporal patternIs your pain constant or intermittent? If intermittent, frequency and duration of episodes; variability according to time of day, etc.

6. Aggravating factors What factors make you pain worse?

7. Alleviating factors What factors decrease your pain?

8. Associated symptomsWhat other sensations are associated with your pain (e.g., nausea, vomiting, dizziness, weakness, incontinence, itching, vasomotor changes)?

9. Previous methods of treatmentWhat treatments have you tried for your pain, e.g., medications, behavioral strategies or alternative therapies such as acupuncture, massage, herbal therapies? How effective have they been?

10. Impact of pain on quality of lifeWhat effect has your pain had on your quality of life? This information many not be feasible to gather on the initial evaluation, due to time or pain intensity, but should be gathered on subsequent patient contact. Areas to assess include mood, sleep, appetite, functional status/activities of daily living.

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Pain Assessment ToolsPain Assessment Tools

• Universal Pain Assessment Tool

– Visual / analog / linguistic pain scoring

– Self-report or interview

http://www.partnersagainstpain.com/hcp/pain-assessment/tools.aspx. Used for educational purposes only.

Pain and Function Assessment ToolsPain and Function Assessment Tools

• Graded Chronic Pain Scale– Pain and function

assessment

Von Korff M. Chronic Pain Assessment in Epidemiologic and Health Services Research: Empirical Bases and New Directions. Handbook of Pain Assessment: Third Edition. Dennis C. Turk and Ronald Melzack, Editors. Guilford Press, New York., In presshttp://www.agencymeddirectors.wa.gov/Files/OpioidGdline.pdf. Used for educational purposes only.

Primary Care StrategiesPrimary Care Strategies

• If not already using pain assessment tools, then start with

– Chronic Pain Scale

– Assess pain and function at start and during therapy

• Consider having patients complete the Brief Pain Inventory at each visit while in the waiting room

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Paradigm Shift from Reducing Pain to Increasing FunctionParadigm Shift from Reducing Pain to Increasing Function

• Pain relief should improve function

• Lack of functional improvement always indicates treatment failure or other problems, e.g., misuse, diversion, addiction, mood disorders, side effects, etc.

FSMB | Responsible Opioid PrescribingTM: A Clinician’s Guide. Available at: http://www.fsmb.org/book/.

Outcomes to AssessOutcomes to Assess

• Progress towards therapeutic goals

• Changes in functional status

• Presence of opioid-related adverse effects

• Changes in underlying pain condition

• Changes in medical or psychological comorbidities

• Opioid tolerance

• Aberrant behaviors, addiction, diversion

The Goal of treatment in chronic pain is

to Improve Function

and Control the Pain

with minimal

side effects

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A Depiction of How Therapeutic Choices May Affect Pain PathwaysA Depiction of How Therapeutic Choices May Affect Pain Pathways

Multiple Pathways of Pain Transmission Provide Multiple Targets for Pain ReliefMultiple Pathways of Pain Transmission Provide Multiple Targets for Pain Relief

Inhibiting ascending pathways1-4,6

• Opioids†

• Local anesthetics• Antiepileptics7

• NSAIDs/acetaminophen

*Theoretical mechanisms of action†It is well established that opioids inhibit the ascending trans-mission of nociceptive signals. Additional mechanisms have been reported in the literature, including the activation of descending inhibitory pathways and modulation of limbic system activity.1,3,4,6

1. National Pharmaceutical Council, Joint Commission on Accreditation of Healthcare Organizations. Pain: current understanding of assessment, management, and treatments. http://www.npcnow.org/resources/PDFs/painmonograph.pdf. December 2001. Accessed March 7, 2008.. 2.Pyati S, Gan TJ. Perioperative pain management. CNS Drugs.2007;21(3):185-211. 3. Vanderah TW. Pathophysiology of pain. Med Clin N Am. 2007;91:1-12. 4. Woolf CJ. Pain: moving from symptom control toward mechanism-specific pharmacologic management. Ann Intern Med. 2004;140(6):441-451. 5. Pertovaara A, Almeida A. Descending inhibitory systems. In: Cervero F, Jensen TS, eds. Pain: Handbook of Clinical Neurology. Vol 81. 3rd series. New York, NY: Elsevier; 2006:179-192. 6. Gutstein HB, Akil H. Opioid analgesics. In: Bruntin LL, ed. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 11th ed. New York, NY: McGraw-Hill; 2006. 7. Knotkova H, Pappagallo M. Adjuvant analgesics. Med Clin N Am. 2007;91:113-124.

Enhancing descending pathways1,3-5

• Norepinephrine reuptake inhibitors• Serotonin reuptake inhibitors• Tricyclic antidepressants• Opioids†

Undertreatment of Pain May Involve Multiple FactorsUndertreatment of Pain May Involve Multiple Factors

Combination of factors

Physician factors

Patient factors

Fear of disciplinary action or prosecution1-3

Potential for abuse2,9

Lack of training in opioid titration8

Fear of addiction, tolerance & side effects10

Socioeconomic and psychological factors1-7,10

Poor patientknowledge10

Communication between physician and patient10

Governmental and public policy on payment for opioid analgesics5,10

Undertreatment of chronic pain

1. Richard J. Reidenberg MM. J Pain Symptom Manag. 2005;29:206-212.2. Gilson AM et al. J Pain. 2007;8:682-691.3. Jung B. Reidenberg MM. Pain Med. 2006;7:353-357.4. McCracken LM, et al. J Pain. 2006; 7:726-734.5. Primm BJ, et al. J Natl Med Assoc. 2004;96:1152-1161.

6. Edwards CL, et al. Pain. 2001;94:133-137.7. Green CR, et al. J Pain. 2005;6:689-699.8. Mercadante S. Eur J Pain. 2007;11:823-830.9. Manchikanti L. Pain Phys. 2006;9:287-321.10. Glachen M. J Am Board Fam Pract. 2001;14:211-218.

Special Considerations: Pregnant WomenManaging Chronic Pain in Pregnant Women is Challenging,and Affects Both Mother and Fetus

Special Considerations: Pregnant WomenManaging Chronic Pain in Pregnant Women is Challenging,and Affects Both Mother and Fetus

• Potential risks of opioid therapy to the newborn include:– Low birth weight– Premature birth– Hypoxic-ischemic brain injury

• Given these potential risks, clinicians should:– Counsel women of childbearing potential about risks & benefits of opioid therapy during

pregnancy & after delivery– Encourage minimal/no opioid use during pregnancy unless potential benefits outweigh risks

• If chronic opioid therapy is used during pregnancy, anticipate and manage risks to the patient and newborns

Chou R, et al. J Pain. 2009;10:113-130.

– Neonatal death– Prolonged QT syndrome– Neonatal opioid withdrawal syndrome

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Special Considerations: Children (<18 years)Special Considerations: Children (<18 years)• Safety and effectiveness of most ER/LA opioids unestablished

– Pediatric analgesic trials pose challenges– Transdermal fentanyl approved in children aged ≥2 yrs

• Most opioid studies focus on inpatient safety– Opioids are common sources of drug error

• Opioid indications are primarily life-limiting conditions– Few children with chronic pain due to non-life-limiting conditions should receive

opioids

• When prescribing opioids to children:– Consult pediatric palliative care team or pediatric pain specialist or refer to a

specialized multidisciplinary pain clinicBerde CB, et al. Pediatrics. 2012;129:354-64. Gregoire MC, et al. Pain Res Manag 2013;18:47-50. Mc Donnell C. Pain Res Manag. 2011;16:93-8. Slater ME, et al. Pain Med. 2010;11:207-14.

American Geriatrics Society Panel on the Pharmacological Management of Persistent Pain in Older Persons. J Am Geriatr Soc. 2009;57:1331-46. Chou R, et al. J Pain. 2009;10:113-130.

• Respiratory depression more likely in elderly, cachectic, or debilitated patients– Altered pharmacokinetics due to poor fat stores, muscle wasting, or altered clearance

– Monitor closely, particularly when

• Initiating & titrating ER/LA opioids

• Given concomitantly w/ other drugs that depress respiration

– Reduce starting dose to 1/3 to 1/2 the usual dosage in debilitated, non-opioid-tolerant patients

– Titrate dose cautiously

• Older adults more likely to develop constipation– Routinely initiate a bowel regimen before it develops

• Is patient/caregiver likely to manage opioid therapy responsibly?

Special Considerations: Elderly PatientsDoes Patient Have Medical Problems That Increase Riskof Opioid-related AEs?

“Nothing is intrinsically good or evil but its manner of usage may make it so”

Thomas Aquinas

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Opioid Risk Tool (ORT) Opioid Risk Tool (ORT) Category Risk Factor Score if

FemaleScore if

Male

Family History of Substance AbuseAlcoholIllegal DrugsPrescription Drugs

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334

Personal History of Substance AbuseAlcoholIllegal DrugsPrescription Drugs

345

345

Age Age 16-45 years 1 1

History of Preadolescent Sexual Abuse 3 0

Psychological DiseaseADD, OCD, Bipolar Disorder, SchizophreniaDepression

2

1

2

1

Total Risk Score

OCD, obsessive compulsive disorder.

Total Score Risk Category• Low Risk 0–3• Moderate Risk 4–7 • High Risk ≥8

Webster LR, et al. Pain Med. 2005;6(6):432-442. Opioid Risk Tool. www.partnersagainstpain.com/printouts/Opioid_Risk_Tool.pdf. Accessed January 8, 2013. Reprinted with permission: Lynn Webster, MD.

SOAPP — Sample QuestionsSOAPP — Sample Questions

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? 0 1 2 3 4

2. How often do you smoke a cigarette within an hour after you wake up? 0 1 2 3 4

3. How often have you taken medication other than the way that it was prescribed? 0 1 2 3 4

4. How often have you used illegal drugs (for example, marijuana, cocaine, etc)in the past five years? 0 1 2 3 4

5. How often, in your lifetime, have you had legal problems or been arrested? 0 1 2 3 4

Used for educational purposes only.

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; Chang Y-P, Compton P. Addict Sci Clin Pract. 2013;8:21; Boscarino JA, et al. Addiction. 2010;105(10):1776–1782.

BIOLOGICAL

• Age ≤45 years

• Gender

• Family history of prescription drug or alcohol abuse

• Cigarette smoking

• Sleep disorder

PSYCHIATRIC

• Substance use disorder

• Preadolescent sexual abuse (in women)

• Major psychiatric disorder (e.g., personality disorder, anxiety or depressive disorder, bipolar disorder)

SOCIAL

• Prior legal problems

• History of motor vehicle accidents

• Poor family support

• Involvement in a problematic subculture

Risk Factors for Aberrant Behaviors/HarmRisk Factors for Aberrant Behaviors/Harm

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• History of treated substance abuse

• Significant family history of substance abuse

• Past/Comorbid psychological disorder

• History of treated substance abuse

• Significant family history of substance abuse

• Past/Comorbid psychological disorder

Moderate Risk

Stratify RiskStratify Risk

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

Consider referring high-risk patients or any patient you have concerns about to a pain specialist

Primary Care StrategiesPrimary Care Strategies• If not using any risk assessment tools, then start with

– ORT to screen for potential for ADRBs

– PHQ-9 to screen for depression

– CAGE-AID to screen for alcohol and/or drug problems

– PEG for pain, function, and quality of life

• For monitoring at follow-up visits, start with– 2-4 weeks determined by risk

• Check state prescription monitoring program at first visit and continuously monitor during treatment (interval often stipulated by medical board)

• Comply with local regulations and laws

Know the Risk Factors for Respiratory DepressionKnow the Risk Factors for Respiratory Depression• Generally preceded by sedation and decreased respiratory rate

• Risk factors for respiratory depression include:

The Joint Commission. Sentinel Event Alert. August 8, 2012;49. www.jointcommission.org.

Sleep apnea or a sleep disorder diagnosis

Morbid obesity with a high risk of sleep apnea Snoring

Risk increases with age (>60) No recent opioid usePost-surgery

(particularly upper abdominal or thoracic)

Use of other sedating agents (CNS depressants), such as

benzodiazepines and alcohol

Preexisting pulmonary or cardiac disease or dysfunction

or major organ failureSmoking

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Post-activity Survey - Part 1Post-activity Survey - Part 1

Examples of nociceptive pain include which of the following?

1. Irritable bowel syndrome, pelvic pain syndrome, interstitial cystitis

2. Rheumatoid arthritis, gout, neck and back pain with structural pathology

3. Acute herpes zoster, postoperative pain, radiculopathy

4. All of the above


When assessing patients in pain, the main focus should be on:

1. Eliminating side effects of pain medications

2. Reducing dosages of pain medications

3. Restoring the patient’s functional status

4. Looking for signs of medication misuse/abuse/diversion


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BreakBreak• The onsite evaluation form can be found in your syllabus and must be

completed to receive credit – please feel free to take it out and start this during the break

• If you have not done so already - please be sure to include your 3-digit keypad number on the evaluation form

Components to an Effective Treatment Plan and General Principals of

Nonpharmacologic Approaches

Components to an Effective Treatment Plan and General Principals of

Nonpharmacologic Approaches

Principles of Responsible Opioid PrescribingTreatment Plan Principles of Responsible Opioid PrescribingTreatment 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

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Principles of Pain Therapy SelectionPrinciples of Pain Therapy Selection

• Standard of care for particular pain conditions and pain patients

• Consider therapies that may provide a better risk-benefit profile

• Patient comorbidities

• Ability of patient to adhere to the rules of therapy

Side effectsRisk of abuse,

misuse, diversionLack of pain relief Pain relief

Improved functionDecreased use of

healthcare resources

Maximal Benefit

Minimal Risk

Fine PG, Portenoy RK. A clinical guide to opioid analgesia. United States of America: Vendome Group, LLC; 2007.

The treatment goals associated with acute pain include:

1. Facilitate recovery from the underlying injury, surgery, or disease

2. Control and reduce pain to acceptable level

3. Restore physical, emotional, and social function

4. Improve quality of life

5. 1 and 2

6. 2 and 4


Treatment GoalsTreatment Goals

• Facilitate recovery from the underlying injury, surgery, or disease – Reduce neuroendocrine stress – Minimize impact of pain on recovery

• Control and reduction of pain to acceptable level

• Minimize pharmacologic side effects • Prevent chronic pain

• Restore function – Physical, emotional, social

• Improve quality of life• Decrease pain

– Treat underlying cause where possible – Minimize medication use

• Correct secondary consequences of pain– Postural deficits, weakness, overuse – Maladaptive behavior, poor coping

http://prc.coh.org/pdf/Goals-FF%205-10.pdf.

ACUTE PAINACUTE PAIN CHRONIC PAINCHRONIC PAIN

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Multimodal Therapeutic

Strategies for Pain and Associated

Disability

Pharmacotherapy

Opioids, nonopioids, adjuvant analgesics

Interventional Approaches

Injections, neurostimulation

Psychological Support

Psychotherapy, group support

Lifestyle Change

Exercise, weight loss

Complementary and Alternative Medicine

Massage, supplements

Physical Medicine and Rehabilitation

Assistive devices, electrotherapy

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 Therapeutic Pain StrategiesMultimodal Therapeutic Pain Strategies

Definition of Integrative Pain TreatmentDefinition of Integrative Pain Treatment

“Integrative pain treatment is the practice of caring for individuals with pain that focuses on the whole person, reaffirms the importance of the relationship between practitioner and patient, uses the least invasive treatments whenever possible, is informed by evidence, and makes use of all appropriate therapeutic approaches, healthcare professionals and disciplines to achieve optimal health and healing.”

– Martha Menard, PhDPAINS, 2013

Interventional Non-interventional

Physical Rehab

Non-pharmacologic OptionsNon-pharmacologic Options

Injections CBT

Comp/Alternative

Neuro-augmentation*

*Exception is Intrathecal Medications

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Pain Treatment Options Non-pharmacologic ApproachPain Treatment Options Non-pharmacologic Approach

• Mind-body therapy

• Heat/cold therapy

• Massage

• Acupuncture

• Tai-chi

• PT/OT

• Transcutaneous electrical nerve stimulator (TENS)

Interventional Therapies for PainInterventional Therapies for Pain

• Epidural Steroid Injection

• Sacroiliac Joint Injection and RFA

• Facet Joint Injection and RFA

• Sympathetic Block

• Celiac and Hypogastric Plexus Block

• Spinal Cord Stimulation

• Spinal Drug Delivery

Therapeutic ConsiderationsSetting PrioritiesTherapeutic ConsiderationsSetting Priorities• Efficacy

– Clinical trial data– Clinical experience

• Safety/tolerability• Ease of use

– Frequency– Patient acceptability

• Cost

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Nonpharmacologic therapies for pain:

1. Have greater efficacy than pharmacologic therapies

2. May include interventional approaches

3. Does not include exercise because exercise stimulates the endorphin chemicals

4. Is best provided in the thousands of interdisciplinary programs in the U.S.


Mind Body Manipulative

Acupuncture

Complementary/AlternativeComplementary/Alternative

Mindfulness Massage/Yoga

Herbals

CBT

Cochrane Reviews (CAM)Cochrane Reviews (CAM)• Touch Therapy: Areas of the body where energy field is weak or congested are assessed,

and practitioner uses his/her hands to direct energy into the field to balance it, thereby relieving pain1

• Music Therapy: Music may have beneficial effects on anxiety, fatigue, depression, pain, and quality of life for patients with cancer; reduces the need for pain medication after surgery2

• P6 Therapy for Post-op Nausea: P6 acupoint stimulation is comparable to antiemetics in preventing postoperative nausea and vomiting after anesthesia and surgery3

• Aromatherapy: Essential oils are massaged into the skin, inhaled, or placed in baths to relieve stress, anxiety, and other ailments, such as pain2

• Caffeine: Use of an analgesic plus caffeine resulted in a higher number of patients with good pain relief compared with use of an analgesic alone4

1.https://cam.cochrane.org/glossary-cam-terms; 2. https://www.cochrane.org/news/music-therapy-strikes-chord; 3. https://www.cochrane.org/CD003281/ANAESTH_wrist-pc6-acupuncture-point-stimulation-prevent-nausea-and-vomiting-after-surgery; 4. https://www.cochrane.org/CD009281/SYMPT_caffeine-analgesic-adjuvant-acute-pain-adults.

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Osteoarthritis Treatment Options Considered Before OpioidsOsteoarthritis Treatment Options Considered Before Opioids• Exercise

– Aquatic/aerobic strengthening• Self-management• Education• Braces• Patellar tape• TENS/acupuncture• Orthopedic consult

• NSAIDs + PPI• NSAIDs + misoprostol• COX-2 inhibitors• Glucosamine• Chondroitin• Topical NSAIDs• Topical capsaicin• IA corticosteroids

COX-2, cyclooxygenase-2; IA, intra-articular; PPI, proton-pump inhibitor; NSAID, nonsteroidal anti-inflammatory drugs; TENS, transcutaneous electrical nerve stimulation.Zhang W, et al. Osteoarthritis Cartilage. 2007;15(9):981-1000.

Spinal Pain Treatment Options Considered Before OpioidsSpinal Pain Treatment Options Considered Before Opioids

• Exercise

• TENS/acupuncture

• Osteopathy

• Facet joint injections

• Root sleeve injections

• Acetaminophen

• NSAIDs

• Antidepressants

• Pregabalin/gabapentin

• Other anticonvulsants

Neuropathic Pain Treatment Options Considered Before OpioidsNeuropathic Pain Treatment Options Considered Before Opioids• Non-drug therapy

– Education– TENS– Spinal cord simulation– Entrapment release

• Pharmacotherapy– TCAs– SNRIs– Pregabalin/gabapentin– Topical lidocaine– Topical capsaicin– NMDA antagonists

NMDA, N-methyl-D-aspartate; SNRI, serotonin norepinephrine reuptake inhibitor; TCA, tricyclic antidepressant.Attal N, et al. Eur J Neurol. 2006;13(11):1153-1169; Cruccu G, et al. Eur J Neurol. 2007;14(9):952-970; Dworkin RH, et al. Pain. 2007;132(3):237-251.

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EFNS, European Federation of Neurological Societies; IASP, International Association for the Study of Pain; NeuPSIG, Neuropathic Pain Special Interest Group

OpioidTramadol

First line

Second line

Third line

TCAGBP/PGB

Lidocaine 5% plaster

SNRI(Opioid)

OpioidLamotrigineCapsaicin

Canadian Pain Society

TCAGBP/PGB

SNRILidocaine 5%

Opioid (except methadone)

TCA, SNRIGBP/PGB

Lidocaine 5%Opioid

(specific circumstances)

EFNS, Europe Neurology IASP NeuPSIG

ParoxetineBupropion

NMDAantagonist

Fourth line Methadone

Neuropathic PainRecommendations of Various SocietiesNeuropathic PainRecommendations of Various Societies

Pharmacotherapeutics IGeneral Principles of Pharmacologic

Analgesic Therapy

Pharmacotherapeutics IGeneral Principles of Pharmacologic

Analgesic Therapy

The most effective and safe way to manage pain with medication is:

1. NSAIDs and antidepressants

2. Anticonvulsants

3. Immediate-release opioids

4. As part of multimodal plan of care


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Selecting Correct Drug for Corresponding Pain TypeSelecting Correct Drug for Corresponding Pain Type

Adapted from: Woolf CJ. Ann Intern Med. 2004;140:441-451.*Chong MS, Bajwa ZH. J Pain Symptom Manage. 2003;25:S4-S11.Used for educational purposes only.

A. Nociceptive Pain

B. Neuropathic Pain

C. Sensory Hypersensitivity

Noxious peripheral

stimuli

Peripheral nerve damage

No known tissue or nerve damage

Abnormal central processing

Multiple mechanisms

Brain

Brain

Brain

Patients may experience multiple pain states simultaneously*

EXAMPLES

• APAP, NSAIDS, antidepressants, opioids

• Antidepressants, anticonvulsants, antiarrhythmic opioids(?)

• Antidepressants (SNRIs), NSAIDs, APAP, opioids

Multimodal TherapyMultimodal Therapy

Although formal pain management treatment protocols are lacking, most experts propose conservative nonpharmacological modalities as primary and adjunctive treatment, with opioids reserved for those patients who fail to respond to other therapies

Used for educational purposes only.

Rational PolypharmacyRational Polypharmacy

Advantages• Multimechanistic effect

• Improved efficacy

• Reduction in end organ toxicity

• Reduction in side effects

• Functional improvement

Disadvantages

• Requires knowledge of drugs, PK data, and pharmacodynamics

• Every analgesic has its own unique adverse event profile

• May increase drug-drug interactions

1. Sinatra RS. Ann Meeting Cleveland Soc of Anesthesiology. Nov 2010.2. Kehlet H, Wilmore DW. Am J Surg. 2002;183:630-41.

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Non-opioids Limited by Efficacy and AEsNon-opioids Limited by Efficacy and AEs

Devries F, et al. Br J Clin Pharm. 2010;70:429-438. Solomon SD, et al. N Engl J Med. 2005;352:1071-1080.Roumie CL, et al. Stroke. 2008;39:2037-2045. Used for educational purposes only.

Considerations for AntidepressantsConsiderations for Antidepressants

• TCAs vs Beer’s Criteria*

• Pharmacology– TCAs

– SNRIs

• See http://www.paindr.com/antidepressant%20chart.pdf

• Drug Interactions to consider– 2D6, 3A4, others

*Beer’s Criteria: guidelines for healthcare professionals to help improve the safety of prescribing medications for older adults.

– SARIs

– Atypicals

AnticonvulsantsAvailable in US, Excluding BenzodiazepinesAnticonvulsantsAvailable in US, Excluding Benzodiazepines

1st Generation Anticonvulsants 2nd / 3rd Generation Anticonvulsants

Carbamazepine (Tegretol, others)Ethosuximide (Zarontin)

PhenobarbitalPhenytoin / Fosphenytoin (Dilantin)

Primidone (Mysoline)Valproic Acid (Depakote, others)

Eslicarbazepine (Aptiom)Ezogabine (Potiga)

Felbamate (Felbatol)Gabapentin (Neurontin)Lacosamide (Vimpat) Lamotrigine (Lamictal)

Levetiracetam (Keppra)Oxcarbazepine (Trileptal, others)

Perampanel (Fycompa)Pregabalin (Lyrica)

Rufinamide (Banzel)Tiagabine (Gabitril)

Topiramate (Topamax, others)Vigabatrin (Sabril)

Zonisamide (Zonegran)

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Inflammation Ongoing Chemical Activation of Pain Sensors

Inflammation Ongoing Chemical Activation of Pain Sensors

Sensitize, activate

NSAIDsCoxibs COX1/2

H+5HTNa+, K+,

Ca2+

channels

C-fiber

NGF

cytokines

Nerve Growth FactorNerve Growth FactorDirect Peripheral, Direct and Indirect Gene Effects Conditions of Tissue Damage, Deep Inputs, NeuromasDirect Peripheral, Direct and Indirect Gene Effects Conditions of Tissue Damage, Deep Inputs, Neuromas

Sensory nerve fiber-sprouting and neuroma-like structures2

Potential functions and mechanisms of action of NGF in development of post-injury pain1

1. Xian CJ, Zhou XF. Nat Clin Pract Rheumatol.. 2009;5:92-98; 2. Jiminez-Andrade JM, Mantyh PW. Arthritis Res Ther. 2012;14:R101..

NGF In Lower Back PainNGF In Lower Back Pain

Takahashi K, et al. Eur Spine J. 2008;17:S428-S431.

Fusion surgery

Sensitization

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Pharmacotherapeutics IIManaging Patients on Opioid Analgesics

Considerations for In-home Naloxone

Pharmacotherapeutics IIManaging Patients on Opioid Analgesics

Considerations for In-home Naloxone

When chronic opioid therapy is initiated:

1. Alternative analgesics should be discontinued

2. An ER/LA formulation should be used

3. A treatment agreement, consent, and urine drug test is required

4. Low doses of immediate release formulations are preferable


Individual Response to TreatmentIndividual Response to Treatment

Argoff CE. Clin J Pain. 2010;26(1):S16-S20.Belle DJ, Singh H. Am Fam Physician. 2008;77(11):1553-1560.

Pharmacogenetics

How the drug affects the body

How the body alters the drug

The science of how genetic variability impactsindividual responses to medications

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4A’s As a Template4A’s As a Template

Patient Response VariabilityPatient Response Variability

Same DiagnosisSame Medications

No Efficacy and Toxicity

Efficacy and No Toxicity

No Efficacy and No Toxicity

Efficacy, but Toxicity

Patient Group

American Medical Association, Arizona Center for Education and Research on Therapeutics, Critical Path Institute. Pharmacogenomics: increasing the safety and effectiveness of drug therapy. Chicago, IL: American Medical Association; 2011. Report 10-0290:5/11:jt. https://crediblemeds.org/files/3913/6973/9557/pgx-brochure2011.pdf.

Looking at pharmacogenetic variability and response, what percentage of the general population has phenotype variability:

1. 5-8%

2. 10-15%

3. 25-35%

4. 40-60%


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Pharmacogenetic Variability and ResponsePharmacogenetic Variability and Response

• General population has 40-60% phenotype variability

• CYP450 enzymes most frequently involved – CYP2D6, CYP2C19, CYP2C9, CYP3A4, CYP1A2,

CYP2E1

• Genetic differences impact 25% of all drugs

Cavallari LH, Limdi NA. Curr Opin Mol Ther. 2009;11(3):243-251. Lynch T, Price A. Am Fam Physician. 2007;76:391-396.Ma JD et al. J Pharm Pract. 2012;25:417-427..

http://www.arupconsult.com/assets/graphics/OpiatesAndOpiodMetabolism.jpg. Used for educational purposes only.

Opiates and Opioid MetabolismOpiates and Opioid Metabolism

How would you proceed if you inherited a patient prescribed both a benzodiazepine for sleep and high-dose opioids after 9 spinal surgeries?

1. Continue both as prescribed2. Reduce the dosages of both medications3. Discontinue the opioid or benzodiazepine therapy 4. Consider an alternative medication, such as an

anticonvulsant or low-dose trazodone


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Benzodiazepines and Chronic Pain PatientsBenzodiazepines and Chronic Pain Patients• Enhance the respiratory depressant effects of opioids

– Frequently co-prescribed with opioids (up to 50% of patients)• In 1 population, 80% of patients prescribed high-dose opioids were co-prescribed

benzodiazepines

• More common in chronic pain patients with substance use disorders

• Consider an alternative– For anxiety disorders

– When a sleep aid is indicated, e.g., an anticonvulsant or low-dose trazodone• For patients with neuropathic pain, low-dose trazodone at bedtime may be dually

beneficial

Webster LR. Pain Med. 2013;14:959-961. Webster LR, et al. Postgraduate Med. 2015;127:27-32. Deyo RA, et al. J Am Board Fam Med. 2011;24:717-727. King SA, Strain JJ. Clin J Pain. 1990;6:143-147. Manchikanti L, et al. Pain Physician. 2009;12:259-267. Braden JB, et al. Arch Intern Med. 2010;170:1425-1432. Dasgupta N. Opioid analgesic prescribing and overdose mortality in North Carolina [dissertation]. Chapel Hill, NC: University of North Carolina at Chapel Hill; 2013. Weisner CM, et al. Pain. 2009;145:287-293.

Opioids for Chronic PainOpioids for Chronic Pain

• Short-acting (immediate release)– Higher peaks, higher toxicity profiles

– Intermittent effect on hypoadrenal axis

– Possible lower overall 24 hour dose

– Consider toxicity if combo w/ ASA, IBU, or APAP

• Long-acting (ER-LA)– Generally have lower Cmax

– Sleep through night, but greater effect on REM sleep

– Continuous effect at hypoadrenal axis

Managing Opioid Side EffectsManaging Opioid Side EffectsSide Effect Treatment

Constipation Increase fluid intake; use of cathartics, stool softeners, PAMORAs, and nonopioid analgesics

Nausea and vomiting Switch opioid v. use antiemetic / Lower dose

Itching Switch opioid; antihistamines

Edema and sweating Switch opioid

Dizziness Anti vertiginous agents

Confusion Titrate dose; switch opioid; add neuroleptic

Endocrine dysfunction Endocrine monitoring; testosterone replacement

Urinary retention Switch opioid

Risk of falling for the elderly Lower dose; use nonopioid analgesics

Respiratory depression Reduce dose or discontinue

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Select Opioid FormulationsSelect Opioid Formulations

• Available with co-analgesic– Oxycodone, tramadol, codeine,

hydrocodone• Pure m-opioid receptor agonists

– Morphine, hydromorphone, fentanyl, oxycodone, hydrocodone

• Two or more mechanisms– Methadone, levorphanol

• Rapid onset (transmucosal)– Fentanyl

• Immediate release without co-analgesic– Tramadol, oxycodone, tapentadol,

hydrocodone, hydromorphone, oxymorphone, others

• Modified release (long acting)– Morphine, methadone, oxycodone,

hydromorphone, hydrocodone, others• Partial agonists

– Tramadol, pentazocine, butorphanol• Partial agonists/antagonists

– Buprenorphine

Opioid Formulations: Points to ConsiderOpioid Formulations: 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 vs temporal patterns of pain• Issues that influence the opioid selection

– Pain pattern– Genetic factors that can influence metabolism– Comorbid medical conditions that may alter drug metabolism or clearance– Past history with opioid therapy and route of administration issues

• Adherence and care-giving issues• Cost and convenience

• Full impact cannot be realized until all opioids are abuse-deterrent

• FDA’s goal: ADFs for all major opioids

Abuse-deterrent formulations (ADFs) One Component to Address Prescription Opioid EpidemicAbuse-deterrent formulations (ADFs) One Component to Address Prescription Opioid Epidemic

Prescribing Guidelines

Insurance Reform

Physician & Patient Education

Research New Safer Therapies

Prescription Drug

MonitoringAbuse-Deterrent

FormulationsApproach to

Address Opioid Epidemic

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Speed of CNS Entry and Concentration Determines Liking

The “abuse potential” of a drug increases as the value of the AQ increases

Opi

oid

Con

cent

ratio

n

Time

Tmax

Cmax

Webster LR. Drug Discovery and Development. July, 30. 2009.

Cmax / TmaxIn this ratio, as Cmax INCREASES and as Tmax DECREASES, the ratio becomes relatively larger, signaling potentially increased attractiveness as a drug of abuse


In converting patients from one extended release opioid to another extended release opioid:

1. Use conversion tables to determine the exact starting dose of the new opioid

2. Adjust dose of new opioid every 24 hours3. Start the new ER opioid at a lower dose or dose as if the patient

is opioid naïve4. Never use IR opioids during an opioid rotation

Eight Opioid Prescribing Principles for Providers©

Help Minimize Harm Prescribing Opioids and Other PsychotherapeuticsEight Opioid Prescribing Principles for Providers©

Help Minimize Harm Prescribing Opioids and Other Psychotherapeutics

1. Assess patients for risk of abuse before starting opioid therapy and manage accordingly2. Watch for and treat comorbid mental disease if present3. Conventional conversion tables can cause harm and should be used cautiously when rotating

(switching) from one opioid to another4. Avoid combining benzodiazepines with opioids, especially during sleep hours5. Start methadone at a very low dose and titrate slowly regardless of whether your patient is

opioid tolerant or not6. Assess for sleep apnea in patients on high daily doses of methadone or other opioids and in

patients with a predisposition7. Tell patients on long-term opioid therapy to reduce opioid dose during upper respiratory

infections or asthmatic episodes8. Avoid using long-acting opioid formulations for acute, post-operative, or trauma-related pain

Webster LR. Pain Med. 2013;14:959-961.

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Issues with Morphine Equivalent Daily Dose and Opioid ConversionIssues with Morphine Equivalent Daily Dose and Opioid Conversion

• Body weight

• Pharmacogenetic variability

• Drug interactions

• Lack of universal morphine equivalence

Fudin J et al. J Pain Res. 2016;9:153-156.Fudin J et al. Practical Pain Management. Sept. 2012. 46-51.Donner B et al. Pain. 1996;64:527–534.Breitbart W et al. Oncology. 2000;14:695-705.Shaw K, Fudin J. Practical Pain Management. 2013;13(7):61-66.

• Specific opioids that should never have an MEDD

– Methadone

– Buprenorphine

– Tapentadol

– Tramadol

Challenge of Equianalgesic ConversionChallenge of Equianalgesic Conversion

• Tables use for risk stratification and should not be used to establish equianalgesic conversion

• Subjects with limited opioid exposure

• Do not reflect clinical realities of chronic opioidadministration

Pereira J et al. J Pain Symptom Manage. 2001;22:672-687.

Risks for Opioid OverdoseRisks for Opioid Overdose

Substance abuse

High daily morphine

equivalent dose (MED)

Age Gender

Concomitant use of benzodiazepines and/or alcohol with or without

other sedative-hypnotics

Chronic lung disease

Chronic kidney and/or liver impairment

Sleep apnea

Accidental exposure to

young children in the home

Opioid Overdose Risk Assessment Checklist. Kaleo, Inc. May 2014. http://www.evzio.com/pdfs/Evzio-Opioid-Overdose-Risk-Assessment-Checklist.pdf. Evzio [package insert]. Richmond, VA: Kaleo, Inc.; 2014.Substance Abuse and Mental Health Services Administration. SAMHSA Opioid Overdose Prevention Toolkit. HHS Publication No. (SMA) 14-4742. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2014.

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Discussing Continued Lack of BenefitDiscussing Continued Lack of Benefit

• Stress how much you believe / empathize with patient’s pain severity and impact

• Express frustration re: lack of good pill to fix it

• Focus on patient’s strengths

• Encourage therapies for “coping with” pain

• Show commitment to continue caring about patient and pain, even without opioids i.e., you are abandoning the treatment, not the patient

• Schedule close follow-ups during and after taper

Patient unable or unwilling to cooperate

with outpatient taper

Provide sufficient opioid for 1-month taper

or maint until admission

Refer to inpatient or outpatient program or similar service, as

available

CBT, cognitive behavioral therapy; PT, physical therapy.Katz N. Patient Level Opioid Risk Management: A Supplement to the PainEDU.org Manual. Newton, MA: Inflexxion, Inc.; 2007.

Opioid Exit Strategy: Possible PathsOpioid Exit Strategy: Possible Paths

Patient’s behavior consistent with drug

addiction

Refer for addiction management or comanagement

No apparent addiction problem

Patient able to cooperate with office-based taper

Taper gradually over 1 month (Longer tx duration longer taper)

Implement nonopioid pain management (psychosocial support, CBT, PT, nonopioid analgesics)


Co-prescribing of take-home naloxone should be considered for patients:

1. Taking high doses of opioids (≥MME per day)

2. With a legitimate medical need for analgesia, coupled with suspected/confirmed substance abuse

3. Undergoing opioid rotation

4. Discharged from emergency medical care following opioid intoxication/poisoning

5. All of the above

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Consider Take-home NaloxoneConsider Take-home Naloxone• Candidates for a naloxone prescription to use in the event of a

suspected opioid overdose include those:– Taking high doses of opioids

– Taking opioid preparations that may increase risk for overdose; e.g., ER/LA opioids, including methadone

– Undergoing opioid rotation

– Discharged from emergency medical care following opioid intoxication/poisoning

– With a legitimate medical need for analgesia, coupled with suspected/confirmed substance abuse

ER/LA=extended-release/long-actingSubstance Abuse and Mental Health Services Administration. SAMHSA Opioid Overdose Prevention Toolkit. HHS Publication No. (SMA) 14-4742. Rockville, MD. 2014.

Neurobiology of AddictionNeurobiology of Addiction

Definition of TermsDefinition 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, e.g., getting high

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

Dependency• Physical neuroadaptation to an exogenous substance or • Associated Abstinence Syndrome

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

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Which of the following is true?1. All aberrant behaviors are signs of addiction

2. All aberrant behaviors are signs of abuse

3. All patients on opioids eventually show signs of aberrant behaviors

4. All people with an opioid addiction misuse/abuse opioids

5. All people who misuse/abuse opioids are also opioid addicts

Opioid Use Disorder (OUD)Opioid Use Disorder (OUD)• DSM-I (1952-1968) – “Addiction” is usually symptomatic of a personality disorder.

• DSM-II (1968-1980) – “Addiction” requires evidence of habitual use ... withdrawal symptoms are not the only evidence of dependence.

• DSM-III (1980-1994) – Essential feature of “Opioid Abuse” ... pattern of pathological use for at least one month ... impairment in social or occupational functioning ... “Opioid Dependence” essential feature is tolerance or withdrawal.

• DSM-IV (1994-2000) – “Opioid Dependence” includes ... compulsive, prolonged self-administration of opioid substances ... for no legitimate medical purpose ... doses that are greatly in excess of the amount needed for pain relief.

• DSM-V (2013-Present) – Categories of substance abuse and substance dependence have been eliminated and replaced with an overarching new category of “substance use disorders” with the specific substance defining the disorder.– Tolerance and withdrawal that previously defined dependence are normal responses.

Triangle of the Disease of Abuse/AddictionTriangle of the Disease of Abuse/Addiction

Genetics

Social /Environment

Drug Properties

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Vulnerability Factor: Drug PropertiesVulnerability Factor: Drug Properties

• Drug-induced effect

• On/Off; frequency

• Rate and quantity of dopamine release

Drug Properties

Kreek MJ. Update on the Neurobiological Linkages between Pain and Chemical Dependency. Pain Management and Clinical Dependency. December 7-9, 2000.Gardner E. Neurophysiology of Chemical Dependence. Pain Management and Clinical Dependency. December 7-9, 2000.

Adapted with permission. Webster publication pending

Vulnerability Factor: EnvironmentVulnerability Factor: Environment

• Set, setting• Cuing• Peer pressure• Stress, stressors• Home


Adapted with permission Webster publication pending

Environment

Vulnerability Factor: GeneticsVulnerability Factor: Genetics

• Approximately 50%• Many polymorphisms• Comorbidity with

mental disorders

Genetics


Adapted with permission Webster publication pending

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Outpatient Treatment Program (OTP) Example: Methadone ClinicOutpatient Treatment Program (OTP) Example: Methadone Clinic

• Most common approach used worldwide

• Intensive treatment program

• Recommended for high-risk patients

• Required evaluations with psychiatrist/counseling

• Patients present daily for observed medication administration• OTP’s can offer both methadone and buprenorphine

• Cash ONLY ($12/day)

• May earn right to “carry” or take home medication for a few days

www.samhsa.gov/medication-assisted-treatment/treatment.

Buprenorphine Methadone NaltrexonePharmacology

Opioid agonist activity μ, Partial agonist μ N/A

Opioid antagonist activity κ, ƍ N/A μ, κ, ƍ

NE reuptake blockade N/A N/A

NMDA inhibition N/A N/A

Pharmacokinetics

Half-life 32-36 hours 15-60 hours 5-10 days

Metabolic pathway3A4 medicated N-dealkylation to

norbuprenorphine and glucuronidation

3A4, 2B6, 2C19 mediated N-demethylation to 2-ethylidene-1,5-

dimethyl-3,3-diphenylpyrrolidene (EDDP)

6β-naltrexol mediated by dihydrodiol dehydrogenase to glucuronidation

Excretion Urine (30%); Feces (69%) Urine (30-50%); Feces (20-70%) Urine (50-80%); Feces (20%)

Opioid chemistry Dehydroxylated phenanthrene Diphenylheptane Dehydroxylated phenanthrene

Dosing SL, Buccal PO IMPO equivalent dose to 30 mg/day of PO morphine 1 mg SL 7.5 mg PO N/A

Starting Dose Up to 8 mg 40 mg 380 mg

Usual Maintenance Dose 8-16 mg 80-120 mg 380 mg

Atkinson T, et al. Clin Ther. 2013;35:1669-1689.

MAT Pharmacology/Pharmacokinetics

Office-Based Opioid Treatment (OBOT) Example: Suboxone ClinicOffice-Based Opioid Treatment (OBOT) Example: Suboxone Clinic• DATA 2000 allows physicians to prescribe buprenorphine for OUD in office

practice– 24 hours of training, submit waiver notification form, DEA assigns X license #

– 1st year 30 patients

– NOI-Request increase to 100 patients

• Comprehensive Addiction Recovery Act (CARA) Effective 7/22/2016 – Section 303 – authorizes NPs and PAs to obtain waiver for DEA X license

• 42 CFR Part A (RIN 0930-AA22)-HHS Rule Effective 8/6/2016– Increase to 275 patients

www.samhsa.gov/medication-assisted-treatment/treatment.

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Buprenorphine Prescribing Is IncreasingBuprenorphine Prescribing Is Increasing• Traditional opioid

prescribing is declining

• DEA announced mandatory 25% reduction in production of opioids from pharmaceutical companies

• Result of decreased prescribing

• Buprenorphine prescribing is increasing– Opioid Use Disorder (OUD)

Probuphine® (5/26/16) Bunavail® (6/6/2014) Zubsolv® (7/3/2013) Suboxone®

• Sublingual tablet (10/8/2002)• Buccal Film (8/30/2010)

– Chronic Pain Belbuca ® (10/13/2015) Butrans ® (6/30/2010)

www.dea.gov/press-releases/2018/08/16/justice-department-dea-propose-significant-opioid-manufacturing-reduction.

Patient/provider counseling strategies include all of the following except:

1. Cognitive Behavioral Therapy

2. Motivational Interviewing

3. CAP Counseling

4. Individual Counseling

5. Community Reinforcement Approach

Polling Question 13

Provider/Patient Counseling StrategiesProvider/Patient Counseling Strategies• Contingency Management (CM)

– Employs stimulus control and positive reinforcement to change behavior

• Cognitive Behavioral Therapy (CBT)– Problem-solving approach to modify dysfunctional emotions, behaviors, and thoughts

• Community Reinforcement Approach (CRA)– Aims to eliminate positive reinforcement (PR) for substance use, and promote PR for

abstinence

• Motivational Interviewing (MI)– Helps solve ambivalent feelings and insecurities to find internal motivation needed

• Individual Counseling• 12-Step Facilitation (AA, NA)

– Guidelines inconsistent in value assessment of 12-step facilitation

www.drugabuse.gov/publications/effective-treatments-opioid-addiction/effective-treatments-opioid-addiction.

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Big Tent - Mental health; addictions; children to older adults; not for profits, government, and peer run; housing, and school and employment services; hospital and community based; prevention, treatment, and recovery supports.

The National Council for Behavioral Health The National Council for Behavioral Health

• Serving 10 million + adults, children and families with mental illnesses and/or addictions.

• Drive mental health and addictions policy, practice, and education initiatives that improve access to effective care

The National Council for Behavioral Health Who Are WeThe National Council for Behavioral Health Who Are We• Over 3,000 Members providing or supporting treatment for Mental

Illnesses and Addiction

• Services– Mental Health First Aid – over 1 million trained

– Center for Integrated Health Solutions (HHS)

– CDC National Networks

– Improving Business & Clinical Practices

– Advocacy and Policy

– Medical Director Institute

National Council Resources National Council Resources

• Dedicated Webpages

• Infographics

• Assessment Tools

• Training and consultation services

• Online Training

• Medical Directors Institutehttps://www.thenationalcouncil.org/opioid-use-disorders/

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Dedicated Website Dedicated Website

• Interactive map of drug use trends

• State sponsored programs

• Infographics

https://www.thenationalcouncil.org/opioid-use-disorders/

Resources: Infographics Resources: Infographics

https://www.thenationalcouncil.org/opioid-use-disorders/

Medical Director Institute Medical Director Institute

• Psychiatric Shortage: Causes and Solutions

• Medication Matters: Causes and Solutions to Medical Non-Adherence

Publications

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Strategic Partnerships Strategic Partnerships

• American Academy of Addiction Psychiatry (AAAP)

• Opioid Response Network

• Physician’s Clinical Support System (PCSS)

• National Association of Recovery Residences (NARR)

• Addiction Technology Transfer Centers (ATTC)

Physician’s Clinical Support System (PCSS)Physician’s Clinical Support System (PCSS)

https://pcssnow.org/

Opioid Response NetworkOpioid Response Network

https://opioidresponsenetwork.org/

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General Resources General Resources • CDC guidelines for prescribing opioids for chronic pain

https://www.cdc.gov/drugoverdose/pdf/Guidelines_Factsheet-a.pdf

• CDC Recommendations for Nonopioid Treatments in the Management of Chronic Painhttps://emergency.cdc.gov/coca/calls/2016/callinfo_072716.asp

• SAMHSA’s Center for Integrated Health Solutionshttps://www.integration.samhsa.gov/clinical-practice/pain-management

Thank You Thank You

CONTACT INFORMATION

Aaron M. Williams, [email protected]

202-684-7462

SummarySummary• Chronic pain is a high prevalence/low priority disease state that

requires comprehensive HCP education to improve

• Chronic pain assessment and treatment is function and goal-oriented

• Effective treatment employs multimodal therapy potentially including interventional, nonpharmacologic, and nonopioid options

• Pain pharmacotherapy emphasizes nonopioid adjunct medications through evidence-based targeting of pain mechanism

• Opioid therapy is reserved for severe refractory pain, emphasizing risk mitigation and individualized therapy as part of multimodal treatment

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Post-activity Survey – Part 2Post-activity Survey – Part 2

The treatment goals associated with acute pain include:

1. Facilitate recovery from the underlying injury, surgery, or disease

2. Control and reduce pain to acceptable level3. Restore physical, emotional, and social function4. Improve quality of life5. 1 and 26. 2 and 4


Nonpharmacologic therapies for pain:

1. Have greater efficacy than pharmacologic therapies

2. May include interventional approaches

3. Does not include exercise because exercise stimulates the endorphin chemicals

4. Is best provided in the thousands of interdisciplinary programs in the U.S.


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The most effective and safe way to manage pain with medication is:

1. NSAIDs and antidepressants

2. Anticonvulsants

3. Immediate-release opioids

4. As part of multimodal plan of care


When chronic opioid therapy is initiated:

1. Alternative analgesics should be discontinued

2. An ER/LA formulation should be used

3. A treatment agreement, consent, and urine drug test is required

4. Low doses of immediate release formulations are preferable


Looking at pharmacogenetic variability and response, what percentage of the general population has phenotype variability:

1. 5-8%

2. 10-15%

3. 25-35%

4. 40-60%


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How would you proceed if you inherited a patient prescribed a benzodiazepine for sleep and high-dose opioids after 9 spinal surgeries?

1. Continue both as prescribed2. Reduce the dosages of both medications3. Discontinue the opioid or benzodiazepine therapy 4. Consider an alternative medication, such as an

anticonvulsant or low-dose trazodone



In converting patients from one extended release opioid to another extended release opioid:

1. Use conversion tables to determine the exact starting dose of the new opioid

2. Adjust dose of new opioid every 24 hours3. Start the new ER opioid at a lower dose or dose as if the patient

is opioid naïve4. Never use IR opioids during an opioid rotation


Co-prescribing of take-home naloxone should be considered for patients:

1. Taking high doses of opioids (≥MME per day)

2. With a legitimate medical need for analgesia, coupled with suspected/confirmed substance abuse

3. Undergoing opioid rotation

4. Discharged from emergency medical care following opioid intoxication/poisoning

5. All of the above

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Which of the following is true?1. All aberrant behaviors are signs of addiction

2. All aberrant behaviors are signs of abuse

3. All patients on opioids eventually show signs of aberrant behaviors

4. All people with an opioid addiction misuse/abuse opioids

5. All people who misuse/abuse opioids are also opioid addicts

Patient/provider counseling strategies include all of the following except:

1. Cognitive Behavioral Therapy

2. Motivational Interviewing

3. CAP Counseling

4. Individual Counseling

5. Community Reinforcement Approach

Polling Question 12

Evaluation RemindersEvaluation Reminders• The onsite evaluation form must be completed to receive credit

• If seeking MOC credit, in addition to completing the onsite evaluation form, please visit www.rockpointe.com/remsmoc (this link is also provided on page 4 of your syllabus)

• You must include your 3-digit keypad number on the evaluation form

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Thank you for joining us today!

Please remember to turn in your completed

EVALUATION FORM.

Your participation will help shape future CME/CE activities.

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