Objectives 1. Describe the prescribing guidelines created by the CDC and the impact on treatment of pain. Chronic Pain Management Jill Duffy, ARNP 2. Explain the importance of establishing a clear diagnosis prior to prescribing opioids for chronic pain. 3. Describe the pain treatment ladder for patients with chronic pain. 4. Describe patient-provider shared responsibility while prescribing medications for chronic pain. 5. Describe the classes of medications that are utilized in the treatment of chronic pain. History of Pain I have no disclosures to make. Derived from Greek POINE goddess of revenge and Roman POENA spirit of punishment Definition of Pain An unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage. (International Association for the Study of Pain, Merskey, 1986) Pain is whatever the experiencing person says it is, existing whenever he says it does. (McCaffery, 1968) CDC Guideline for Prescribing Opioids for Chronic Pain United States, 2016 Centers for Disease Control and Prevention Morbidity and Motality Weekly Report, March 15, 2016 1
Guideline #1 DETERMINING WHEN TO INITIATE OR CONTINUE OPIOIDS FOR CHRONIC PAIN Nonpharmacological therapy and nonopioid pharmacologic therapy are preferred for chronic pain. Clinicians should consider opioid therapy only if expected benefits for both pain and function are anticipated to outweigh risks to the patient. If opioids are used, they should be combined with nonpharmacological therapy and nonopioid pharmacologic therapy as appropriate. No drug should be prescribed for any disorder without weighing the risk versus benefit. Guideline #2 Before starting opioid therapy for chronic pain, clinicians should establish treatment goals with all patients, including realistic goals for pain and function, and should consider how therapy will be discontinued if benefits do not outweigh risks. Clinicians should continue opioid therapy only if there is clinically meaningful improvement in pain and function that outweighs risks to patient safety. Sometimes the goal is comfort care and delayed dysfunction (Spinal cord injury, Parkinson s disease, etc.) Guideline #3 Before starting and periodically during opioid therapy, clinicians should discuss with patients known risks and realistic benefits of opioid therapy and patient and clinician responsibilities for managing therapy. Guideline #4 When starting opioid therapy for chronic pain, clinicians should prescribe immediate-release opioids instead of extended-release/longacting (ER/LA) opioids. OPIOID SELECTION, DOSAGE, DURATION, FOLLOW-UP, AND DISCONTINUATION 2
Guideline #5 When opioids are started, clinicians should prescribe the lowest effective dosage. Clinicians should use caution when prescribing opioids at any dosage, should carefully reassess evidence of individual benefits and risks when increasing dosage to > 50 morphine milligram equivalents (MME)/day, and should avoid increasing dosage to >90 MME/day or carefully justify a decision to titrate dosage to >90 MME/day. The daily dosing is important, but also individual There is no universally accepted MME Schatman M, Fudin J. The Myth of Morphine Equivalent Daily Dosage. Medscape. 2016 May. http://www.medscape.com/viewarticle/863477 Shaw K, Fudin J. Evaluation and Comparison of Online Equianalgesic Opioid Dose Conversion Calculators. Practical Pain Management. 2013 August: 13(7):61-66 Rennick A, Atkinson T, Cimino, NM, Strassels, SA, McPherson ML, Fudin J. Variability in Opioid Equivalence Calculations. Pain Medicine 2016:17:892-898. Guideline #6 Long-term opioid use often begins with treatment of acute pain. When opioids are used for acute pain, clinicians should prescribe the lowest effective dose of immediaterelease opioids and should prescribe no greater quantity than needed for the expected duration of pain severe enough to require opioids. Three days of less will often be sufficient; more than seven days will rarely be needed. Guideline #7 Clinicians should evaluate benefits and harms with patients within 1-4 weeks of starting opioid therapy for chronic pain or of dose escalation. Clinicians should evaluate benefits and harms of continued therapy with patients every 3 months or more frequently. If benefits do not outweigh harms of continued opioid therapy, clinicians should optimize other therapies and work with patients to taper opioids to lower dosages or to taper and discontinue opioids. Some times one opioid doesn t work or is not well tolerated, or both, and there may be another opioid that is a better option. ASSESSING RISK AND ADDRESSING HARMS OF OPIOID USE 3
Guideline #8 Before starting and periodically during continuation of opioid therapy, clinicians should evaluate risk factors for opioid-related harms. Clinicians should incorporate into the management plan strategies to mitigate risk, including considering offering naloxone wen factors that increase risk for opioid overdose, such as history of overdose, history of substance abuse disorder, higher opioid dosages (>50 MME/day), or concurrent benzodiazepine use, are present. Guideline #9 Clinicians should review the patient s history of controlled substance prescriptions using state prescription drug monitoring program (PDMP) data to determine whether the patient is receiving opioid dosages or dangerous combinations that put him or her at high risk for overdose. Clinicians should review PDMP data when starting opioid therapy for chronic pain and periodically during opioid therapy for chronic pain, ranging from every prescription to every three months. Guideline #10 When prescribing opioids for chronic pain, clinicians should used urine drug testing before starting opioid therapy and consider urine drug testing at least annually to assess for prescribed medications as well as other controlled prescription drugs and illicit drugs. Guideline #11 Clinicians should avoid prescribing opioid pain medications and benzodiazepines concurrently whenever possible. Alcohol Guideline #12 Approximately 20-30% of opioid related deaths involved alcohol. Alcohol may cause some ER/LA formulations to release the drug all at once. Combination of alcohol and single drug class in ER visits Opioid pain relievers, 26,446 (13.8%) Oxycodone/combinations: 10,160 Hydrocodone/combinations: 7,251 Benzodiazepines, 38,244 (34.1%) Alprazolam: 13,063 Clonazepam: 7,734 Combination of benzos, opioids, alcohol Of 3883 opioid related deaths, 860 (22.1%) involved alcohol Of 1512 benzo related deaths, 324 (21.4%) involved alcohol. Clinicians should offer or arrange evidencebased treatment (usually medication-assisted treatment with buprenorphine or methadone in combination with behavioral therapies) for patients with opioid use disorder. Jones C, Paulozzi LJ, Mack KA. Alcohol Involvement in Opioid Pain Reliever and Benzodiazepine Drug Abuse- Related Emergency Department Related Deaths United States, 2010. Morbidity and Mortality Weekly Report. October 10, 2014:63(40); 881-885. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6340a1.htm 4
Types of Pain: Nocioceptive Pain that is related to an unpleasant stimulus or one that would be unpleasant if prolonged. Stubbing your toe Hand in ice water Somatic Originates in skin, muscles, bone, or soft tissue Closely aligned to type and extent of injury Visceral Activation of specialized fibers: organs and viscera Pain due to damaged or dysfunctional nerves Burning Stabbing Shooting Types of Pain: Neuropathic Peripheral neuropathy Central neuropathic pain Spinal cord injury Post-stroke pain Cancer Pain Tumor related Pain syndromes Treatment related Inflammatory Pain Chemical buildup of irritants Tissue damage Inflammation Other types of Pain Sympathetically Maintained Pain Abnormal connections between pain fibers and sympathetic nerve fibers Edema Temperature Blood flow regulation Pain Treatment Ladder Pain Treatment Ladder Interventional Pain NSAIDS OTC Medications Physical Therapy Manipulation TENS Muscle Relaxants Nerve Blocks Behavioral Programs Corrective Surgery Long Term Oral Opioids Implantable therapy spinal cord stimulation Implantable therapy interspinal drug infusion Neuroablation (chemical or surgical) 5
Surgery or injury causes inflammation Pain: Acute to Chronic Sensitization with sustained activation of the PNF Peripheral Nociceptive Fibers Activated Structural remodeling with CNS neuroplasticity and hyperactivty Transient Activation with sustained currents Central Sensitization Syndrome Multiple and complex mechanisms Temporal summation or windup Long-term potentiation Heterosynaptic potentiation Amplification from one set of nociceptive fibers to other sets not stimulated Dysfunctional descending pain inhibition Activations of descending facilitatory pathway Medications Acute pain can respond best to analgesic pharmacotherapy Chronic pain responds better to multimodal therapy Bony pain = NSAID with opioid Neuropathic pain = TCAs, anticonvulsants, local anesthetics, topical capsaicin, nerve blocks Infections damage = incision and drainage, anti-infectives GI spasm = anticholinergic agents Constipation = stimulating laxatives Lymphedema = physical therapy, compression Use of Every Medication is an EXPERIMENT Potential benefit outweighs the potential harm Consider initiation a trial to determine the outcome Continue only if benefits outweigh the risks Lessen adverse outcomes Set patient expectations about their therapy Cost to benefit issues considered by clinicians Patient Preference Inquire about patient belief and preferences Prior experience Other s response to opioids Misconceptions Medication does not cure pain Variability in response to analgesics Counsel on the need to adjust medication and dosing to optimize response Treat the Cause Misconception to increase the dose Until pain is relieved adequately Until unacceptable side effects Myofascial pain = physical therapy 6
Synergy and Potentiation Combinations can increase response with synergy and potentiation Bone pain = NSAID and opioid Neuropathic pain = tricyclic antidepressants or anticonvulsant medications with opioid Two drugs act together to produce enhanced action NSAID provides peripheral antiinflammatory activity Opioid acts largely centally One drug enhances the effect of the other Acetaminophen acts at the serotonergic system in the brain Analgesics Acetaminophen Caution above 2 grams/day Modulates COX-1, COX-2, COX-3 enzymes in the brain Impacts neurogenic inflammation or serotonergic mechanisms Can boost the endocannabinoid system No to NSAIDs NSAIDS Most widely prescribed medications in the world with over 2 dozen commercially available in the US Action Inhibit prostaglandin synthesis Analgesic, anti-inflammatory, antipyretic Caution Renal failure Hepatic disease Try at full dose for 3 weeks then rotate if no response Classes Salicylates Aspirin Choline magnesium trisaliclate (Trilisate, Tricosal) Diflunisal (Dolobid) Salsalate (Disalcid) Propionic Acid derivatives Fenoprofen (Nalfon Fluribiprofen (Ansaid) Ibuprofen (Advil, Motrin, others) Ketoprofen (Orudis) Naproxen (Naprosyn, others) Naproxen Sodium (Aleve, Anaprox) Oxaprozin (Daypro) Fenamates Diclofenac (Voltaren) Tolmetin (Tolectin) Ketoralac (Toradol) Mefanamic acid (Ponstel) Meclofenamate (Meclomen) Enolic acid derivatives (oxicams) Meloxicam (Mobic) Piroxicam (Feldene) Nabumetone (Relefen) Acetic acid derivatives Etodolac (Lodine) Indomethacin (Indocin) Sulindac (Clinoril) COX-2 selective NSAID (coxib) Celecoxib (Celebrex) 7
Skeletal Muscle Relaxants Sedative Carisoprodol (Soma) Chlorzoxazone (Parafon Forte) Metaxalone (Skelaxin) Methocaramal (Robaxin) TCA-like Cyclobenzaprine (Flexaril) Antihistamine Orphenadrine (Norflex) GABA-type Diazepam (Valium) Baclofen (Lioresal) Central Alpha-2 Agonist Tizanidine (Zanaflex) Antidepressants Selective Serotonin Receptor Inhibitors (SSRIs) Citalopram Escitalopram Fluoxetine Fluvoxamine Paroxetine HCL Paroxetine mesylate Sertraline Serotonin and norepinephrine reuptake inhibitors (SNRIs) Desvenlafaxine Duloxetine Venlafaxine Tricyclic Antidepressants (TCAs) Amitriptyline Clomipramine Desipramine Imipramine Maprotiline Nortriptyline Gabapentin Pregabalin Carbamazepine Oxcarbazepine Lamotrigine Other Valproic acid Sodium valproate Topiramate Levetiracetam Zonisamide Tiagabine Lacosamide Anticonvulsants Capsaicin Lidocaine Ketamine Topical Agents Opioids Opioids 8
Opioids Opioids Tramadol only opioid studied for use in fibromyalgia Positive effect on pain and improved quality of life Serotonin and norepinepherine effects Metabolized by CYP450 isoenzyme 2D6 Codeine 10% of population lack enzyme to convert to morphine (CYP450 isoenzyme 2D6) Ultra-metabolism may result in toxic effects Tapentadol (Nucynta) Noradrenergic receptor effects Metabolized via hepatic glucuronidation with less drug-drug interactions Buprenorphine Partial opioid agonist Indicated for moderate to severe pain in patients requiring a continuous, around the clock opioid analgesic for an extended period of time. Osteoarthritis, low back pain Schedule III Advantages Lower abuse potential Less dangerous in an overdose Causes fewer withdrawal symptoms Buprenorphine Patch Each patch is meant to be worn for 7 days Rotate sites: upper outer arm, upper chest, upper back or side of the chest Initial dose in opioid-naïve patients is always 5 mcg/hr Conversion typically less than 30 MME/day start with 5 mcg/hr and 30-80 MME/day start with 10 mcg/hr. Buprenorphine Patch Available in the following strengths: 5 mcg/hr 7.5 mcg/hr 10 mcg/hr 15 mcg/hr 20 mcg/hr Do not increase for at least 72 hours Buprenorphine Film Buccal film Dosing every 12 hours Available in the following strengths: 75, 150, 300, 450, 600, 750, 900 mcg Opioid naïve start at 75 mcg daily or q12hr. Opioid tolerant Taper down opioid to 30 MME/day or less. 30 MME/day start 75 mcg daily or q12hr 30-89 MME/day start 150 mcg q12hr 90-160 MME/day start 300 mcg q12hr Max dose 900 mcg q12hr Increase dosing after 4 days by 150 mcg every 12 hours 9
Changing Opioids Lack of therapeutic response Development of adverse effects Change in patient status Other considerations Opioid/formulation availability Formulary issues Patient/family heath care beliefs Opioid rotation Explain the Change Improved pain management ER/LA show less troughs/valleys Enhanced adherence to opioid therapy Improved patient outcomes Better analgesic effects Better functional status Fewer adverse effects Opioid Conversion Process 1. Assess pain. 2. Determine the total daily dose of current opioid long acting and short acting 3. Decide which opioid analgesic with be used for the new agent. 4. Consult established conversion table to determine new dose. 5. Individualize dosage based on assessment information. 6. Patient follow-up and reassessment (7-14 days) Abuse-Deterrent Opioid Formulations Deter abuse by potential abusers 70% of illegal users obtain by stealing, purchasing illegally, or receiving from family or friends. Dump effect: acceleration associated with rapid high Higher peak over shorter time National Addictions Vigilance Intervention and Prevention Program (NAVIPPRO) Track drugs of abuse Current popularity Preferred method of abuse Abuse Deterrent Opioids Add pharmaceutical or chemical component Deter ability to physically alter the drug s original form to extract the active ingredient Crushing, chewing, mixing with a solvent Examples Morphine + naltrexone in a sequestered core Oxycodone + hydrophophobic fatty and waxy materials = microspheres Oxymorphone ER with crush resistant properties Aversion technology = add niacin to oxcodone Moorman-Li, R; Motycka, CA; Inge, LD; Congdon, JM; Hobson, S; Pokropski, B. A Review of Abuse- Deterrent Opioids for Chronic Nonmalignant Pain. Pharmacy and Therapeutics, 2012 July 37(7); 412-418 MAKING IT WORK 10
The 15-Minute Office Visit At Each Visit Acute: Identify, diagnose with examination, treat, improvement Chronic: Complete resolution is not likely Ask What do you think I can do to help your pain? Ask about pain and record the level Determine the functional status and if treatment is improving function Modify treatment according to response Use non-pharmacological and pharmacological methods for pain control Explain the available options and foster a positive attitude in the patient toward dealing with the pain Bonica s Management of Pain. 2010. Streamlining the Visit Assessment Tools Substance Abuse Screening The Screener and Opioid Assessment for Patients with Pain (SOAPP) Opioid Risk Tool (ORT) Goal Setting and Plan of Action Symptom management Functional improvement The 4 As of Treatment Sucess Analgesia or pain score Activities of daily living or functional outcome that is meaningful to patient Adverse events Aberrant behavior Thank you. Any questions? 11