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TAPERING OPIOIDS, BUPRENORPHINE and the ROLE of the PATIENT’S PHARMACIST

Ann LaPolla, DNP, JD, MPH , Legal Counsel NADDI Opioid Task ForceDean Healey, RN DOPL Investigator

Co-chairs Utah NADDI Opioid Task Force

What is pain?

  In 1968, McCaffery defined pain as “whatever the experiencing person says it is, existing whenever s/he says it does”.

  Pain is a subjective experience with no objective measures.

  The patient, not clinician, is the authority on the pain and that his or her self-report is the most reliable indicator of pain.

  In 1979, the International Association for the Study of Pain (IASP) definition of pain: an “unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.’’

  Pain is a complex experience with multiple dimensions.

Pathophysiology of injury

  Injury to tissue causes cells to break down and release various tissue byproducts and mediators of inflammation (e.g., prostaglandins, substance P, bradykinin, histamine, serotonin, cytokines).

Acute Pain

  Complex, unpleasant experience with emotional and cognitive, as well as sensory, features that occur in response to tissue trauma

  Associated with pathology

  Usually resolves with healing of the underlying injury

  Usually nociceptive, but may be neuropathic

  Examples: trauma, surgery, labor, medical procedures, and acute disease states

Chronic Pain

  Pain that extends beyond the period of healing

  Levels of identified pathology are often low and insufficient to explain the presence and/or extent of the pain

  Disrupts sleep and normal living

  Ceases to serve a protective function

  Degrades health and functional capability

  Chronic pain serves no adaptive purpose

Chronic pain

  May be nociceptive, neuropathic, or both

  Caused by injury (trauma or surgery), malignant conditions, or chronic non-life-threatening conditions (arthritis, fibromyalgia, neuropathy)

  May exist de novo with no apparent cause

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Neuropathic pain

  Caused by aberrant signal processing in the peripheral or central nervous system

  May be peripheral or central

  Reflects nervous system injury or impairment

  Pathologic pain because it serves no purpose

Pathophysiology of chronic NP  Occurs when pathophysiologic changes become

independent of the inciting event

  Sensitization plays an important role in this process

  Nerve injury triggers changes in the CNS that can persist indefinitely

  Central sensitization explains why NP is often disproportionate to the stimulus or occurs when no identifiable stimulus exists

Central Sensitization

  State of spinal neuron hyperexcitability (may be caused by opioids)

  May be caused by tissue injury, nerve injury or both

  Ongoing nociceptive input from the periphery is needed to maintain it

  “Wind-up”: repeated stimulation of C- nociceptors initially causes a gradual increase in the frequency of DH neuron firing

  Activation of N-methyl D-aspartate (NMDA) receptors

Importance of peripheral sensitization

  Role in central sensitization

  Role in clinical pain states:

  Hyperalgesia: increased response to a painful stimulus (may be caused by opioids)

  Allodynia: pain caused by a normally innocuous stimulus (air, clothing in Complex Regional Pain Syndrome “CRPS”)

Characteristics of NP

  Continuous or episodic

  Burning, tingling, prickling, shooting, electric shock-like, jabbing, squeezing, deep aching, spasm, or cold

Categories of neuropathic pain

  Painful peripheral mononeuropathy and polyneuropathy (diabetic neuropathy, carpal tunnel)

  Deafferentation pain (postmastectomy pain, phantom limb pain)

  Sympathetically maintained pain (CRPS, postherpetic neuralgia)

  Central pain (post-stroke pain, cancer pain, MS pain)

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Causes

  Metabolic disorders (e.g., diabetes)

  Toxins (e.g., alcohol chemotherapy agents)

  Infection (e.g., HIV, herpes zoster)

  Trauma

  Compressive (nerve entrapment)

  Autoimmune and hereditary diseases

Clinical states

  Diabetic neuropathy

  Alcoholic neuropathy

  Post-herpetic neuralgia

  Carpal tunnel syndrome

Deafferentation Pain

  Pain that is due to a loss of afferent input

  Quality: burning, cramping, crushing, aching, stabbing or shooting

  Hyperpathia/Hyperalgesia : exaggerated response to painful stimuli

  Dysesthesia: MS, altered, uncomfortable sensation that may not be painful

  Other abnormal sensations

Causes

  Damage to a peripheral nerve, ganglion, or plexus

  CNS disease or injury (occasional)

Clinical states

  Phantom limb pain

  Post-mastectomy pain

Sympathetically Maintained Pain

  Quality: burning, throbbing, pressing, or shooting

  Allodynia

  Hyperalgesia

  Associated ANS (automatic nervous system) dysregulation and trophic changes (changes in skin, tissue, muscles, bones, i.e. wasting, thinning, thickening)

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Causes

  Peripheral nerve damage: CRPS

  Sympathetic efferent (motor) innervation

  Stimulation of nerves by circulating catecholamines

Clinical states

  CRPS

  Phantom limb pain

  Post herpetic neuralgia

  Some metabolic neuropathies

Central Pain

  Quality: burning, numbing, tingling, shooting

  Spontaneous and steady or evoked

  +/- sensory loss

  Allodynia

  Hyperalgesia

Causes

  Ischemia (e.g., stroke)

  Tumors

  Trauma: spinal cord injury

  Demyelination

Clinical states

  Post-stroke pain

  Some cancer pain

  Pain associated with multiple sclerosis

Prevalence of pain

  Pain is the most common reason why patients seek medical care

  An estimated 100 million Americans suffer from chronic pain

  Most common types of chronic pain are neck and low back pain, myofascial/FM pain, HA, arthritis and neuropathic pain

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Pain is a public health problem

  Chronic pain is a chronic illness

  Affects at least 100 million American adults

  Costs society $560–$635 billion annually

  Federal and state costs almost $100 billion annually

Consequences of untreated pain

  Endocrine/metabolic: altered release of multiple hormones leading to metabolic disturbances as evidenced by weight loss, fever, shock, increased RR and HR

  CV: increased HR, vascular resistance, BP, myocardial oxygen demand, hyper coagulation leading to CP, MI and DVT

  Respiratory: decreased air flow 2/2 reflex muscle spasm and splinting that limit respiratory efforts leading to atelectasis and PNA

Consequence of untreated pain

  GI: decreased gastric motility leading to delayed gastric emptying, constipation, anorexia, ileus

  Musculoskeletal: muscle spasms, impaired muscle mobility and function leading to immobility, weakness and fatigue

  Immune: impaired immune system leading to infection

  GU: abnormal release of hormones that affect UO, fluid volume and electrolyte balance leading to decreased UO, HTN and electrolyte imbalances

Prevention of chronic pain

  Poorly controlled acute pain may lead to chronic pain

  Chronic neuropathic pain (post-mastectomy pain, post-thoracotomy pain, phantom limb pain) may be caused by lack of appropriate pain management and/or failure of early rehabilitation

  The risk of post herpetic neuralgia may be increased with inadequate pain control of acute herpes zoster

Importance of prevention of chronic pain

  Patient: quality of life 2/2 decreased risk of a chronic disease

  Society: decreased lost dollars in productivity

  Health care system: decreased cost

  Insurance companies: decreased expenditures

Inadequate control of pain interferes with quality of life

  Ability to carry out activities of daily living, i.e. work, relationships, hobbies

  Adverse psychological consequences, i.e. anxiety, fear, anger, depression, or cognitive dysfunction

  Suicidal ideation

  Family members report varying levels of helplessness, frustration, fatigue

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Financial consequences of under treated pain

  Patients, families, health care organizations, and society bear the financial burden

  Patients with chronic pain are five times as likely as those without chronic pain to use health care services

  Lost productivity and income; patients are often unemployed or underemployed

  Leading cause of medically related work absenteeism; results in more than 50 million lost work days per year in the United States

Misconceptions about pain

  Physical or behavioral signs of pain (e.g., abnormal vital signs, grimacing, limping) are more reliable indicators of pain than patient self-report.

  Elderly or cognitively impaired patients cannot use pain intensity rating scales.

  Pain does not exist in the absence of physical or behavioral signs or detectable tissue damage.

  Pain without an obvious physical cause, or that is more severe than expected based on findings, is usually psychogenic.

  Comparable stimuli produce the same level of pain in all individuals (i.e., a uniform pain threshold exists).

  Prior experience with pain teaches a person to be more tolerant of pain.

Misconceptions about pain II

  Analgesics should be withheld until the cause of the pain is established.

  Non-cancer pain is not as severe as cancer pain.

  Patients who are knowledgeable about pain medications, are frequent emergency department patrons, or have been taking opioids for a long time are necessarily addicts or “drug seekers.”

  Use of opioids in patients with pain will cause them to become addicted.

  Patients who respond to a placebo drug are malingering.

  Neonates, infants, and young children have decreased pain sensation.

2019 HHS DRAFT REPORT

  “Draft Report on Pain Management Best Practices: Updates, Gaps, Inconsistencies, and Recommendations” hhs.gov

  Comments closed 04/2019

  Pain Management Best Practices Inter-Agency Task Force: 29 experts

  Comprehensive Addiction and Recovery Act (CARA) 2016

HHS Task Force: Concepts

  Balanced pain management: biopsychosocial model of care

  Individualized patient-centered care

  Appropriate risk assessment

  Multidisciplinary

  Stigma

  Education

HHS Best Clinical Practices

  Medications

  Buprenorphine

  FDA approved for pain

  partial agonist at mu opioid receptor

  decreased risk for respiratory depression

  safer than full agonists

  antagonist at the kappa receptor decreasing anxiety and depression

  problems with insurance prior-auth

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Chronic Pain Assessment

  Use Non-pharmacologic and Non-opioid Pharmacologic Therapies as Alternative Treatments to Opioids

  Opioid medications are not the appropriate first line of treatment for most patients with chronic pain

  Other non-pharmacologic and non-opioid pharmacologic therapies, should be tried and the outcomes of those therapies documented first

  Opioid therapy should be considered only when other potentially safer and more effective therapies are proven inadequate

  Combination therapies with opioids

  Assure that use of opioid pain treatment does not interfere with early implementation of functional restoration programs, such as exercise and physical therapy

Identify if Benefits Outweigh the Risks

  Consider initial and ongoing risks associated with opioid exposure based on:

  age of the patient

  history of substance use disorder

  psychiatric, physical, or medical co-morbidities.

  Only consider opioid therapy when expected benefits of pain improvement, function, and quality of life are anticipated to outweigh the risks

Definitions

  Tolerance: a state of adaptation in which exposure to a drug induces changes that result in a diminution of one or more of the drug’s effects over time

  Physical dependence: a state of adaptation that often includes tolerance and is manifested by a drug class specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing blood level of the drug, and/or administration of an antagonist

Addiction (SUD)

  A primary, chronic, neurobiological disease, with genetic (40-60%), psychosocial, and environmental factors influencing its development and manifestations

  Characterized by behaviors that include one or more of the following: impaired control over drug use, compulsive use, continued use despite harm, and craving

Triaging patients

  Is the patient taking opioids?

  No: use other modalities, avoid starting opioids, assess and treat co-morbidities: obesity, diabetes, PVD, PAD, heart failure, HTN

  Yes: assess for underlying qualifying medical conditions, calculate MME, assess for hyperalgesia, assess for addiction, assess for risk (ORT), assess for misuse, assess for sleep apnea, OIC, adverse effects of opioids, review and verify medical records and imaging, talk to treating physicians

Triaging patients: medical conditions

  Low back pain, headaches/migraines, FM: opioids are not recommended, not effective and may increase pain, multiple modalities

  Acute pain: assess dose, fix what can be fixed, multiple treatment modalities, establish taper plan or plan to transition to buprenorphine, opioids should be used only 3-10 days depending on surgical procedure, SLVAMC discharges all surgical patients on BUP

  Chronic pain: identify type (s) (NP, AP, CS, PS), fix what can be fixed, re-image and re-evaluate, taper plan, transition to buprenorphine, multiple modalities, chronic pain patients can taper off opioids

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Palliative Care and Hospice

  Palliative Care: life-limiting condition, goals are comfort and maintenance of function, establish taper plan, lowest effective dose to maintain function and quality of life, buprenorphine trial-well tolerated

  Hospice: < 6 months to live, only a 6 month benefit, patients transition to palliative care to requalify for hospice benefit, patients are now graduating from hospice, taper plan, buprenorphine is well-tolerated

Education and Counseling

  Crucial at every interaction

  Assess reading level of individual patient

  Identify barriers to learning

  Individualized learning plans

  Mandatory classes:

  Opioid overdose recognition and Narcan administration class 2 x year

  Opioid class 2 x year: safety, medications, adverse effects, choices

  Healthy Lifestyles Class: nutrition, physical activity, motivation, pain management skills

  Substance Use Disorder Class every month

Support Groups

  Opioid Taper Support Group

  Buprenorphine Support Group

  SUD Support Group

Patient Shaming (Stigma)

  Don’t do it: vulnerable fragile patients with co-existing psychiatric issues

  risk of self harm (abandonment of Suboxone Rx and return to heroin) and suicide

  patients feel worthless, embarrassed, loss of motivation to continue taper and/or treatment

  Risk to HCP, patients and 3rd parties

  Use techniques to de-escalate the situation

  Call the prescriber, if prescriber won’t cooperate call DOPL or DEA

  Refuse the prescription

  don’t personalize it

  safety reasons

  call for help

Tapering Opioids

  Dignity and Respect

  Identify underlying medical, psychological and social issues

  Fix what can be fixed: use multi-modal approach

  Rapid tapers do not work

  Slow process, may take 2-4 years for LTHD opioids

  Must develop trust

  Listen to the patient

Reasons to Taper Opioids

  Patient safety issues: aberrant behaviors, SUD, OD, self harm, harm to others

  Opioids no longer control patient’s pain

  Patient desires to stop opioid therapy

  Opioids were never medically necessary

  Opioids are no longer medically necessary

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The conundrum of opioid tapering in long-term opioid therapy for chronic pain: A commentary Ajay Manhapra, MD, Albert J. Arias, MD and Jane C. Ballantyne, MD

https://doi.org/10.1080/08897077.2017.1381663

Complex Persistent Dependence in LTOT: grey area between dependence and addictionManifested by desire to continue or increase opioids despite provider’s recommendations to taper and discontinueSigns and symptoms: worsening pain, worsening function, sleep disturbances, protracted withdrawals with taperBuprenorphine recommended: long half-life, ceiling on adverse effects, breaks reward cycle, allows safer and more comfortable taper

Rapid tapers

  Inpatient detox: OD, self harm, harm to others, aberrant behaviors, physician abandonment of practice

  Buprenorphine transition stops withdrawals and provides pain relief

  Must evaluate continued treatment with MAT for long term success

  Must continue therapy and psychological support for best outcome

Tapering Opioids

  Part of tapering is holding the taper

  Encourage alternative modalities and skills for pain control

  Therapy and counseling are crucial

  Written Taper Plan

  Continual reassessment of patient’s tolerance of taper

  Realistic goals

Example Opioid Taper PlanInsurance: University of Utah MedicaidRestricted Medicaid: YCase Worker: XXXXRestricted pharmacies: Y University of Utah UNIPalliative Care: consult completed with U PalliativeTransfer from hospice: NDiagnoses: 60% 3rd degree burn, necrotic LLE, failed fem-fem bypassAffiliated providers: vascular surgery, PCP, U of U psychiatry, OP Burn Clinic, U of Utah anesthesiaFailed therapies: PT, fem-fem bypass, multiple failed graftsFuture therapy: skin grafting scheduled in one weekCurrent therapies: Xarelto, high dose oxycodone and methadoneEstimated length of opioid therapy: unknownCurrent MME: patient stopped opioids 40 hours agoTaper plan: transition to buprenorphine for pain management, Buprenorphine Induction today: tolerated fair; notified patient that I will not prescribe high dose >90 MME to patient; he should be through withdrawals; if he returns to high dose opioids, he is at risk for overdose and deathGoal MME: 0Patient has been counseled regarding the need to taper for health and safety reasons. CDC and American Pain Academy Guidelines reviewed with patient. Risks of long term opioid therapy discussed with patient. Please do not fill opioids, benzodiazepines or Soma for patient written by other providers. Patient is restricted to: Ann E. LaPolla, APRNOpioid Therapy Contract Requested by Pharmacy: YOpioid Therapy Contract faxed to pharmacy: Y

Benefits of multi-disciplinary teams

  Members: multiple providers (PCP and specialists), pharmacist, psych, social worker, chaplain

  Essential in complex patients with co-morbidities

  Effective and efficient care for patients, rapid response to patient needs

  Continuity of care

  Ease of transition between levels of care: acute inpatient to palliative to hospice to palliative

Multidisciplinary Teams: Managing and tapering opioids

  Risk-benefit analysis of opioids

  Probable length of opioid therapy

  Lowest effective dose

  Alternatives to opioid therapy

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NADDI OPIOID TASK FORCE

  Multidisciplinary Teams

  Composed of members from DOPL, DEA, FBI, AG Office, local law enforcement, case management teams from insurance providers and hospitals, ED physicians, Pain Management physicians, Addiction and Recovery HCP, Psychiatrists, Pharmacists

  Non-disciplinary approach, prevention

  Team 1: intervention, triage and placement of patients when providers are removed from practice or abandon practice

  Team 2: support for providers caring for LTHD patients

  Benefit: Regulatory support for taper and transition plans, health and safety of patients, health and safety of providers

Acute on chronic pain case study

  38-year-old female s/p pancreatic transplant, end-stage renal disease on HD, heart failure, pulmonary HTN, osteoporosis, tube feeds for low albumin, recent MVC cervical spine pain, MRI confirms severe central stenosis 2/2 multiple herniated discs and vertebral displacement, scheduled for immediate cervical fusion

  Chronic pain issues: severe pain during and following HD 2/2 noncompliance with fluid restriction

  Current opioid therapy: Oxycodone 5 mg po bid following HD, #24 for 30 days

  Goal of current opioid therapy: increase compliance with HD, hx of missing HD 2/2 pain

Case study

  Team members: PCP, pain management, nephrology, cardiology, pulmonology, GI, transplant, neurosurgery, anesthesiology psych, nutrition, pharmacy, social work

  Medication issues: on transplant meds, immunosuppressed, no steroids, no NSAIDs

  Allergies: NKMA

  Current issue: post-operative pain management for multi-level fusion

Case study

  Desired outcome: effective intra- and post-operative pain management, taper back to baseline MME of < 10

  Effective pain management: allows appropriate progress in rehabilitation and return to prior level of functioning

  Remember goal: compliance with HD

Communication between team members

  Notes faxed to all team members

  One pharmacist for all medications

  Opioid and taper plan faxed to all team members for comments

  Who will manage immediate post-operative pain? pain at discharge? Communicate with pharmacist

  Phone calls between team members for rapid changes

Specific issues with HD patients

  AKF: all patients on HD are palliative

  Patients can choose not to go to HD and die quickly

  Patients require close surveillance for early interventions

  Patients on HD become frustrated and fatigued; more likely to give up

  Not enough evidence to support safety of buprenorphine in HD patients

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BRAVO METHOD OF TAPERING  Anna Lembke, MD Stanford University 2018

  Broaching the subject: empathy, time and addressing fears

  Risk-benefit calculator: function, safety, risks of continuing on opioid therapy

  Addiction happens: difference between dependence and addiction

  Velocity and validation: go slow, engage patients, never go backwards

  Other strategies for controlling pain

Long term high dose opioid taper case study

  2016: 37-year-old male with low back pain presented to clinic on the following medications: Oxycontin 80 mg po qid, Oxycontin 20 mg po qid, Oxycodone 30 mg (11 per day, # 330 per 30 days), Soma 350 mg po qid, clonazepam 1 mg po tid

  No imaging, No PT, No records, MD arrested and clinic closed, patient had been on this dose since age 18, paid cash $300.00 per visit

  MME 1095

Concerns

  No underlying qualifying medical condition, no evaluation

  BZO, Soma, and High MME

  Assessment: accompanied by wife who describes him as a “zombie”, awake, O x 4 occasionally falls asleep during visit, speech is not clear, unable to participate and engage in conversation

Plan

  Lumbar spine films ordered

  MRI ordered + SLR LLE, Strength 3/5 LLE, decreased sensation

  PT

  Interventional Pain

  Surgical evaluation post-MRI

Taper Plan

  Is patient willing to taper?

  Is the patient medically stable to taper? Co-morbidities? IP or OP?

  Family support

  Soma: taper over 2 months

  Clonazepam: psychiatry consult; start taper when off Soma, plan 4-6 month taper

  Discontinue Oxycontin 20 mg qid on first visit MME 120 decrease

  Oxycodone: weekly prescriptions

  COWS every week, clonidine prn

2017 One year assessment

  Oxycodone: 20 mg po 5 x day MME 150

  Oxycontin: 60 mg po bid MME 180

  Dropped 765 MME in one year

  Clonazepam: managed by psychiatry, current dose 0.5 mg po bid and tapering

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2018 Two year assessment

  Oxycodone 15 mg po bid prn MME 45

  Oxycontin 60 mg po bid MME 180

  Decrease of 870 MME over 2 years

  Clonazepam 0.5 (#15 tabs per month)

10/2018 Assessment

  Tapered to Oxycontin 40 mg po bid MME 120

  Unable to taper further, increased pain, anxiety

  Transitioned to buprenorphine 8 mg sl tid; 7 day prescriptions until stable

  2016 MRI large disc herniation with nerve root impingement

  2016 He declined surgery and injections, terrified of needles

2019 Current Assessment

  Buprenorphine 8 mg sl tid, wants to taper after surgery

  Currently receiving injections in preparation for surgery

  Goal is to taper off everything

What role did his pharmacists play?

  Did not fill prescriptions on many occasions 2/2 to safety concerns

  Contacted his previous provider on many occasions

  Counseled him to taper at every encounter

  During the tapering process, supported him with every decrease

  Willing and available to contribute and consult on taper plan

  Entire pharmacy congratulated him when he tapered off opioids

  Pharmacists have been instrumental in tapering 3 additional LTHD to off over the past 2 years

Buprenorphine for Pain

  Use in chronic pain management in US is fairly recent (FDA approved 02/2002); Europe has a 25 year history

  CPG are being developed

  Frequent review of the literature

  HHS support for use for chronic pain

  Be aware of dosing in chronic pain; many patients need microdosing (Butrans patch; Belbuca)

  In office induction; RTC in 2-7 days

  Methadone dose needs to be 40 mg or less, need to bridge with Butrans or microdose buprenorphine

  May use as LA, while tapering SA opioids

  May experience nausea and slight withdrawals (anti-emetic and clonidine for 3-5 days)

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Benefits

  Better long acting control of chronic pain

  Do not wake up with pain

  Eliminates “pill anxiety”

  Improved sleep

  Improved clarity

  Improves anxiety and depression

  Improved quality of life for patients

Issues

  Med review for serotonin syndrome issues

  Partial mu agonist: avoid BZO, Soma; No alcohol

  Still has a street value, be aware of diversion

  Many heroin addicts first use of buprenorphine products is on the street

  Georgia, former USSR, buprenorphine crisis because heroin was inaccessible, IV use

  Recent buprenorphine MD case SLC

  Higher safety profile than full mu agonists but may be lethal in opiate naive patients, children, pets

  May require multiple naloxone doses to reverse 2/2 to high affinity to receptor

Questions

  Questions???