Steven Prakken MD Director Medical Pain Service Duke Pain Medicine
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2 Steven Prakken MD Director Medical Pain Service Duke Pain Medicine
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4 Misuse Abuse Addiction Total Pain Population Webster LR, Webster RM. Pain Med. 2005;6(6):
5 DSM IV Abuse defined as 2 elements to meet criteria. Dependence as 3 elements to meet criteria. DSM V (May 2013) Substance Use Disorders, no abuse vs dependence Mild (2-3), Moderate (4-5) Severe (6 and more) Research impact of DSM IV and V criteria SUD increase since 2012?
6 Pharmacological indicators Tolerance withdrawal Impaired control Greater amount and longer use Unable to quit Time to obtain extensive Craving Social impairment Role failure Use with known social harm Social loss due to use Risky use Use in spite of physical danger Use with continued psych/social harm Severity score -Mild (2-3) -Moderate (4-5) -Severe (6 and more)
7 Rate in last year for 2016, SAMHSA 7.5% of population with SUD (20.1million) 75% with ETOH 37%% with illicit drug 12% with both Rate in Pain and Primary Care 8% - 12%. (Systematic review from 38 studies, with 26% primary care settings, 53% pain clinics) 2017 NSDUH Report, Vowles 2015
8 Percent in Past Year Substance Use Disorder Past Year, Aged 12 or Older and Older 12 to to or Older SAMHSA 2017
9 Pain Reliever Use Disorder Past Year, Aged 12 or Older and Older 12 to to or Older SAMHSA 2017
10 SAMHSA 2017
11 Rate in last year for 2016, SAMHSA 4.4% of population (11.8 mil) No change from % say that their misuse is for pain, tension, sleep, or mood 12% say they use to get high or feel good Rate in Pain and Primary Care 21-29% (Systematic review from 38 studies, with 26% primary care settings, 53% pain clinics) Misuse is not SUD 2017 NSDUH Report, Vowles 2015
12 Past research has found that 29% to 60% of people with opioid addiction report chronic pain. Methadone clinic patients with increased sensitivity to pain. (Fishbain) Peles 2008 Fishbain 2012
13 There is no consistent pattern of differences evident when comparing CNCP patients with a history of SUD versus those without on demographic, pain, or psychiatric variables. Multidisciplinary approach along with UDS, CSRS, frequent visits, limited opioid amount, etc. all reduce risk of misuse Benjamin J. Morasco 2011
14 Slightly higher rate in pain clinics No substantial changes in rate for decades Those w/wo SUD are not clearly different pain patients than others. So how do you handle this in the clinic??
15 SUD has to meet criteria Not a gut check diagnosis mild might be considered abuse Document social/role deterioration Craving of medication, not pain control Using with known harm when they know, not you Checking UDS/CSRS consistently for data Collateral information Risk factors by history ORT, family and personal history Misuse is not SUD
16 Hardest distinction Return to criteria SUD Misuse is not SUD Be CURIOUS as to reason for misuse When, why, hoped for what outcome? Authoritarian intervention usually not therapeutic Sudden medication dose changes are high risk Does not mean no limits approach
17 SAMHSA 2016
18 Opioid stim Depressed and need tx ADHD tx Don t give sleep aides if stimulated by opioid Opioid sedation Anxiety relief relative to pain Helping rumination Sleeping aide MRJ Helping pain and anxiety Misuse is a cue about what they feel is needed So replace it Likely not SUD
19 Does it exist? Duke Pain HU study, N=570, top and bottom 100 of the cohort Overall average of 5 opioid trials per patient 48% at least 1 opioid stimulating 62% at least 1 opioid sedating Oxycodone 24% stim vs MS 9% stim What is the etiology Mu receptor Glial cell Unknown Influence on addiction Influence on OIH
20 Patient short on medication, again! Curious as to why, when, how much, etc Most common reasons (decreasing order) Pain control Impulsivity Poor memory Selling Intervention 3 bottle system Reduced availability Partner holding, shorter scripts Fully random UDS/pill count
21 Curious, what is the story Common reasons Short UDS not accurate Selling Intervention Admission of being short? Then back to previous slide UDS at different parts of script cycle UDS not accurate? No meds of any kind Observed UDS in future Make sure UDS test looks for the missing opioid
22 UDS with meds not currently prescribed Curious as to reason Common reasons Misuse, then to previous slide (pain, mood, etc) Impulsivity Have to have SUD vs misuse of other medication Other prescriber Intervention Clarification of med list or prescribing roles Limitation of current meds if dangerous Medication destruction of old scripts House sweeps by others
23 Morphine and/or fentanyl in UDS = heroin Fentanyl in many SUD products now Metabolites not present Just took pill Dipped pill Not tested for P450 issue Pill count accuracy suspect Pills available for count, street contract
24 Send for SUD evaluation Make sure they will apply criteria Carful if abstinence based in SUD eval if pain patient Find someone that understands pain and opioids Choose safer opioid Tramadol Tapentadol Buprenorphine
25 Partial agonist at Mu very high affinity Strong antagonist at Kappa x more potent than morphine Sublingual and transdermal Bioavailable 40% buccal, 30%SL, 15% transdermal QT prolongation X4 less than methadone Site of action spinal > brain Pergolizzi 2010, Khanna 2015
26 No confusion if you just remember Partial Agonist Will activate receptor only partially Is etiology to any w/d, not naloxone Very high affinity for Mu Will dominate at the receptor Potential precipitated withdrawal Incomplete reversal by naloxone Half life hrs
27 Addiction With Naloxone Bunavail Suboxone Zubsolv Without Naloxone Subutex (least expensive) Pain Butrans Belbuca
28 Respiratory Has ceiling effect, safest opioid Full agonists with up to 11% respiratory depression Constipation Much lower incidence (1-5%) No sphincter of Oddi spasm Use in pancreatic pain? Renal failure Bile elimination No increase in blood levels Hemodialysis does not effect levels Stable pain control Dahan 2010, Shipton 2005, Cuer 1989, Boger 2006, Filtz 2006
29 Cognitive Better visual, psychomotor, cognitive function vs morphine or methadone Less impaired driving Depression Less depressogenic, Active antidepressant effect? Both likely due to Kappa antagonist effect Davis 2012, Soyka 2005, Karp 2014, Mello 1985
30 Immunosuppression Does not - reduce NK cell function Increase cortisol Reduce ACTH levels Change cytokine expression Hormonal impact Does not Reduce testosterone Reduce hormone levels Davis 2012, Aloisi 2011, Bleisener 2005, Hallinan 2009,
31 Tolerance Slower than for morphine and fentanyl Antihyperalgesia Effect on antihyperalgesia >analgesia Reduction vs prevention central sensitization? QTc Methadone up to 29% of patients Methadone 4x buprenorphine for cardiac death Koppert 2005, Vandera 2000, Anchersen 2009
32 Pain Review showing efficacy in 25/26 trials No analgesic ceiling effect Some evidence of no antagonistic effect on other Mu opioid agonists Can use full agonists if need Kappa antagonism may reduce euphoria of others Neuropathic pain Effective in review May work through antihyperalgesia Raffa 2014, Davis 2012, Butler 2013, Induru 2009, Benedetti 1998, Hans 2007, Pergolizzi 2010
33 No Waiver needed for any buprenorphine product if using for disease of pain Butrans FDA approve in 2013 Patch technology 5, 7.5, 10, 15 and 20 mcg/hr 7 day patch Belbuca FDA approved 10/2015 Buccal patch, dissolving 75 to 900 mcg patches
34 Transdermal patch MCG doses of 5, 7.5, 10, 15, 20 Starting dose: 5 mcg if <30mg MEQ 10mcg if MEQ
35 Buprenorphine buccal film MCG doses of 75, 150, 300, 450, 600, 750, 900 For bid dosing
36 MSE dose prior to tapering to 30 mg Less than 30 mg oral MSE mg oral MSE mg oral MSE Greater than 160 mg oral MSE Starting dose 75 mcg every 12 hrs 150 mcg every 12 hrs 300 mcg every 12 hrs Consider alternative tx
37 Clinical application Opioid misuse within pain MRJ or other med use Previous potential SUD Active SUD, non-opioid Street opioid use for pain Death rate Cultural safety Mono vs dual product Buprenorphine cost on Good Rx
38 When using Suboxone/Subutex No waiver needed, for disease of pain Decision to begin buprenorphine Educate about precipitated withdrawal Not naloxone effect Not reversible Consider test dose Start when COWS score mild to moderate If on other opioids Suggest 1-2mg bid start if opioid naïve
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40 Induction for Suboxone or Subutex. STOP full agonist, wait for COWS of >8-10, then. Day 1. 4mg initial dose, repeat in 2 hrs at 2-4mg, may repeat at 2-4 mg in another 2-6 hrs if need, total max of 12 mg if need. May consider smaller initial test dose. Stop at the dose that reverses withdrawal Common first day dose is 8mg Day 2. repeat once the dose that worked day 1, if after 12 mg the first day there was poor response then may add 4mg for 16mg total dose. No higher for a week and then may increase by 2mg every 2-4 days. 16mg most common SUD tx dose 32mg max effective dose
41 Anderson 2017
42 Anderson 2017
43 Questions?
44 death rate (UK study) 57 bup vs 2366 methadone total number.022 vs.137 per 1000rx rates Most with multiple drugs present All MAT, did not break out contributing factors Review of buprenorphine exposures ( ) 6000 exposures (up to 18 y/o) 11 deaths 7 deaths in children under 6 y/o (single med) 4 in y/o (multiple meds) Marteau 2015, Post 2018
45 Agonists Oxycodone, oxymorphone, hydrocodone, morphine, methadone, codeine, fentanyl, tramadol, tapentadol Partial Agonists Buprenorphine?? Antagonists (Mu) Naloxone, naltrexone Agonist/Antagonist Butorphanol, nalbuphine, pentazocine Pergolizzi 2010
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