More than pain: unintended consequences of chronic pain treatment

Transcription

1 More than pain: unintended consequences of chronic pain treatment Marianne Cumming, BSc (Pharm), MSc, MD, DBIM, FALU Senior Vice President, Head Global Life & Health Underwriting January 30, 2017

2 Table of Contents / Agenda Chronic pain: risk assessment Chronic pain: risk classification Chronic pain: treatment Chronic pain: opioid risks Opioid overdose Medical marijuana: update Underwriting risk assessment Unintended consequences: summary 2

3 Chronic pain: risk assessment 3

4 Case: 49 year old male, life insurance applicant Paramedical exam: build lbs, BP 118/68, blood chemistry and urinalysis both unremarkable Occupation: Factory worker Habits: Non-smoker, non-nicotine, no alcohol (history taken) Rx since 2010: oxycodone /acetaminophen (Percocet) 10/325 mg 1-3 daily; fentanyl transdermal patch 75 mg every 72 hours; zolpidem (Ambien) 10 mg nightly APS: back pain, treated by primary care, no interference with activities of daily living, no missed work (these questions were specifically asked) 4

5 Underwriting: asking the right questions and looking for the right answers 5

6 Underwriting considerations: chronic pain Applicant: age, occupation, social, lifestyle Diagnosis: specific cause vs. non-specific Location: localized vs. diffuse Intensity: impact on functioning Duration: short vs. long (>2y) Course: stable, better or worse Medical: history, co-existing conditions Treatment: drug-centric vs. non-drug measures Rx: compliance, misuse, Rx and combinations 6

7 Chronic pain: risk classification 7

8 Chronic pain: definitions persistent pain Pain which lasts beyond the ordinary duration of time that an insult or injury to the body needs to heal Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV): persistent pain for six months International Association for the Study of Pain (IASP): pain without apparent biologic value, persisted beyond normal tissue healing time (3 months) American College of Rheumatology (ACR): widespread or regional pain for at least 3 months American Society of Anesthesiologists: (non-cancer) pain of any etiology, duration beyond expected temporal boundary of tissue injury and normal healing, adversely affecting function or well-being Ranges from minor annoyance to overwhelming life event May adversely affects all aspects of health 8

9 Chronic pain: over 100 million Americans Pain: 63% consult primary care; 20% outpatient visits, 12% all prescriptions US adults: 19% constant or frequent pain > 3 months duration, majority moderate to severe Complementary & alternative medicine: pain conditions represent 6 of the top 10 reasons for use Chronic pain: functional impairment, psychological distress (anxiety, depression), sleep problems; 80% report interference in activities of daily living, 66% negative impact on personal relationships Most common cause of long-term disability. In US, estimated >50 million lost work days/year Opioids use and misuse in chronic pain management is a major public health issue Institute of Medicine, JAMA 2014; 312 9

10 Chronic pain: Measures of function Application, Questionnaires, APS: physical, social function; activities, interests; employment, disability benefits; associated conditions McGill Pain Questionnaire: What Does Your Pain Feel Like? How Does Your Pain Change with Time? How Strong is Your Pain? Visual analog scale (VAS) 10

11 Chronic pain: suicide associations Ideation Chronic low back pain (CLBP) smokers higher risk for suicide ideation vs. nonsmoking with CLBP suicidal ideation (SI) risk greater with heavy smoking and alcohol misuse Fishbain et al. Pain Med Attempt Canadian Community Health Survey, n=36,984 SI or attempt (SA) (past 12 months) associated with >1 chronic pain conditions (esp. migraine) Psychiatric disorder with >1 chronic pain condition, SI and SA significantly increased Ratcliffe et al. Clin J Pain 2008 Completion Chronic pain completed suicide rates higher vs. general population: white men 2X white women 3X white worker s compensation men 3X Fishbain et al. Clin J Pain

12 Chronic pain and mortality, systematic review All-cause mortality Cancer Mildly increased death risk, not statistically significant Smith et al, PLoS ONE 2014 Cardiovascular 12

13 Chronic pain: treatment 13 13

14 Non-steroidal anti-inflammatory drugs: treatment of pain in knee and hip osteoarthritis; meta-analysis 74 randomized trials, almost 60,000 patients NSAIDs, acetaminophen, or placebo for treatment of osteoarthritis pain Outcomes - pain and physical function Confirmed effectiveness: NSAIDS - celecoxib, diclofenac, naproxen Improve pain and function, effects increase with increased dose No benefit with acetaminophen, regardless of dose da Costa BR et al. The Lancet, 17 March

15 NSAIDs, acetaminophen: adverse effects NSAIDs: Two black box warnings GI ulcers: 15% chronic users, Higher risk: past ulcers, high dose or more-ulcerogenic, concurrent steroids, aspirin, anticoagulants; older age; H. pylori, co-morbidities Increase CV (MI) risk: COX2 inhibitors (42%), dose-related, Celecoxib >200mg, ibuprofen 2.4g, diclofenac 150mg/d. Naproxen neutral risk (Kearney, BMJ 2006) May exacerbate hypertension, cause renal failure Acetaminophen (APAP, paracetamol): Potentially fatal liver injury - intentional or unintentional overdose; alcohol use or fasting worsen liver injury Implicated in almost 50% acute liver failure in US, estimated 458 deaths/yr (Lee, Hepatology 2004 ) Usual dose mg Total daily dose limit 3g (3000 mg) In US, lowered from 4g USA (not Canada) by manufacturer due to liver injury risk (J&J, 2011) 15

16 NSAID: ketorolac (Toradol) m/ eugene-monroeravens-marijuana-opioids-toradolnfl/ 16

17 Chronic pain: adjuvants to analgesics, not all are recommended Enhance analgesics Manage other symptoms: nausea, sedation, insomnia, depression, anxiety Treat neuropathic pain Anti-depressants Benzodiazepines Anti-epileptic drugs (AEDs) Muscle relaxants Amitriptyline (Elavil) Buproprion (Wellbutrin) Citalopram (Celexa) Doxepin (Sinequan) Duloxetine (Cymbalta) Fluoxetine (Prozac) Imipramine (Tofranil) Paroxetine (Paxil) Sertraline (Zoloft) Venlafaxine (Effexor) Alprazolam (Xanax) Chlordiazepoxide (Librium) Clonazepam (Klonopin) Clorazepate (Tranxene) Diazepam (Valium) Flurazepam (Dalmane) Lorazepam (Ativan) Oxazepam (Serax) Temazepam (Restoril) Triazolam (Halcion) Carbamazepine (Tegretol) Clonazepam (Klonopin) Gabapentin (Neurontin) Oxycarbazepine (Trileptal) Phenytoin (Dilantin) Pregabalin (Lyrica) Valproate (Depakote) Baclofen (Lioresal) Carisoprodol (Soma) Chlorzoxazone (Parafon Forte) Cyclobenzaprine (Flexeril) Metaxalone (Skelaxin) Methocarbamol (Robaxin) Orphenadrine (Norflex) 17

18 Chronic pain: opioid risks "Every pharmaceutical drug is a dose-dependent poison." Medical Letter

19 Washington Post, November

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21 Common opioids Opioid Trade names Morphine equivalent Morphine Kadian, MS-Contin 1.0 Codeine +acetaminophen (APAP) Tylenol # Fentanyl Duragesic (patch) 2.4 Hydrocodone +APAP Zohydro, Hycodan, Vicodin, Lortab, Lorcet 1.0 Hydromorphone Dilaudid, Exalgo 4.0 Methadone Dolophine Oxycodone +APAP / +ASA OxyContin, Roxicodone, Percocet, Percodan Oxymorphone Opana ER

22 New opioid formulations Drug Abuse deterrent formulation Mechanism Hydrocodone ER Hysingla becomes viscous gel when dissolved Zohydro viscous gel when the capsules are crushed and dissolved Oxycodone ER Oxycontin difficult to crush, break, or dissolve, becomes viscous gel when dissolved Xtampza ER Microspheres resist crush, chew, melted or dissolved difficult to inject Morphine ER Embeda sequestered naltrexone core (opioid antagonist), released if crushed, chewed, or dissolved. Opioid antagonist Formulation Needle-free or auto-injector Naloxone Narcan nasal spray, Evzio pre-filled autoinjector First responders, friends, relatives, emergency treatment overdose 22

23 Abuse-deterrent opioid formulations 23

24 High opioid dose and overdose risk Overdose defined as death, hospitalization, unconsciousness, or respiratory failure Dunn et al. Ann Int Med

25 Opioids: higher dose associated with increased risk road trauma among drivers Ontario Drug Benefit Program, case control study, ages cases road trauma identified over 8 year period Dose-dependent increased risk road trauma in drivers treated with opioids low dose, MEQ, OR 1.21 moderate dose, MEQ, OR 1.29 high dose, MEQ, OR 1.42 Gomes et al, JAMA Intern Med,

26 Mortality with methadone for non-cancer pain Drug Morphine Methadone N 32,742 6,014 Median daily 90 mg 20 mg Deaths Retrospective cohort, TN , mean age 48 (30-74), 58% female 90% indication back or other musculoskeletal pain Methadone vs. morphine: increased risk of death (all-cause) HR 1.46 (95% CI, , p<.001) Low dose: HR 1.59 ( , p=.046) New users: HR 1.38 ( , p=.02) Supports recommendation as not first-line for non-cancer pain Ray et al. JAMA Internal Medicine

27 Opioid overdose 27 27

28 Unintentional injury deaths, USA, 2014 Deaths Unintentional poisoning Motor vehicle traffic deaths Unintentional fall deaths Total unintentional injury deaths Number 38,851 35,398 31, ,053 Per 100,000 population Poisoning deaths surpassed motor vehicle deaths since

29 United States: opioid overdose epidemic, CDC, 2014 Rx OPIOIDS: Deaths - 14,000; Age 25-54, Men more likely to die, gender gap closing; Rx methadone, oxycodone, hydrocodone HEROIN: Deaths - 10,500; Age 18-44, 75% prior Rx opioid misuse, increase use in women, privately insured, higher income Total opioid deaths 2014: > 28,000, 50% Rx opioids : Rx opioids sales nearly quadrupled, with no overall change in amount of pain reported Similar increase in Rx opioid overdose deaths FENTANYL: e.g. Ohio deaths 514 (92 in 2013, 500% increase), illegally manufactured, mixed with heroin or cocaine, Potency: 50x heroin, 100x morphine 29

30 Increases in legitimate pain killer manufacture and sales correlate with treatment admissions and deaths Rates of prescription painkiller sales, deaths and substance abuse treatment admissions ( ) 30

31 Overdose deaths: top 10 drugs involved, US, 2010 & , ,055 Drug Number Percent Drug Number Percent 1 Oxycodone 5, Heroin 10, Methadone 4, Cocaine 5, Cocaine 4, Oxycodone 5, Alprazolam 3, Alprazolam 4, Heroin 3, Fentanyl 4, Morphine 2, Morphine 4, Hydrocodone 2, Methamphetamine 3, Fentanyl 1, Methadone 3, Diazepam 1, Hydrocodone 3, Methamphetamine 1, Diazepam 1, National Vital Statistics Reports, December 20,

32 Overdose deaths still rising: 52,404 in 2015; up from 47,055 in 2014; 5,349 more deaths, 11.4% increase Synthetic opioids other than methadone, 9,580 deaths 72% increase Heroin, 12,989 deaths 21% increase Male Female Male Female 63% (33,091) deaths involved an opioid; 9% decrease in methadone deaths MMWR December 16,

33 Opioid drug monitoring: hide and seek and find Opioid Codeine (prodrug) Morphine Hydrocodone Hydromorphone -- Heroin Oxycodone Oxymorphone -- Methadone -- Fentanyl -- Active metabolites available as Rx Morphine Hydrocodone Hydromorphone Hydromorphone Morphine Oxymorphone Primary care, n=5,240; UDM - 30% aberrant results Rx opioid not detected Opioid not Rx present Non Rx BDZ 12.3 THC Illicit drug Dilute Turner et al, J Gen Intern Med 2014 SAMSHA 5: cannabinoids; cocaine; amphetamines including methamphetamines; opiates - heroin, opium, codeine, morphine; phencyclidine (PCP) Expanded tests: alcohol; barbiturates; benzodiazepines; ecstasy MDMA; hydrocodone, methadone; oxycodone, propoxyphene, others 33

34 Illicitly manufactured fentanyl (IMF): public health threat 34

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36 Medical marijuana: update 36 36

37 Marijuana for medical purposes, US Characteristic Medical use only (AOR) Characteristic Medical use only (AOR) Age (years) Age first use (years) Under Employment Daily use 3.5 Full time 1 State legal status 1.8 Disabled 3.1 Heavy alcohol 0.7 Self-reported health Non-Rx opioid 0.6 Good Stroke 2.8 Fair/poor 1 Anxiety disorder dx 2.1 Compton et al, JAMA, published online December 19,

38 Review: benefits of medical marijuana for pain, small RCTs; Hill KP, JAMA,

39 Chronic marijuana: reviews of medical consequences Hall et al, Drug Test Analysis 2014 Probable adverse effects: dependence (9%) chronic bronchitis (smoked) psychosis (heavy use) impaired education attainment residual cognitive impairment Possible adverse effects: respiratory cancers mood disorders, suicide other illicit drug use Gordon et al, Curr Psychiatry Rep 2013 Probable increased risk viral, some bacterial infections head and neck, lung, bladder cancers decreased lung function, bronchitis myocardial infarction (mixed) arteritis ischemic stroke cognitive impairment 39

40 Medical marijuana, Canada and US Canadian Province Alberta 322 Authorized possession British Columbia 1,372 Manitoba 63 New Brunswick 116 Nfld, Labrador 42 Nova Scotia 619 Ontario 1,873 Quebec 321 Saskatchewan 127 Territories & PEI 29 TOTAL 4,884 Health Canada 2010 <0.2 per 1,000 US State Registered users Colorado 111, Oregon 69, California 572, Michigan 146, Washington 103, Maine 17, Total:19 states & DC No./1,000 state population 1,137, per 1, states & DC have medical marijuana program laws, 11 states with limited access laws procon.org, October 27,

41 Marijuana: ExamOne insurance applicants Urine THC +, gender Urine THC +, cotinine + 24% 76% Males Females 28% 9% 63% Cotinine (-) Males cotinine + Females cotinine + THC positive applicants, January to October 2014, n=3,104, 75% males Mean age 36.5, range years Mean face amount $438,258; range $1,000-$3,000,000 Cotinine positive, n=1,149 (37%), of these 75% males All states represented, top 5: CA, TX, NY, FL, CO, IL, WA, GA, PA, MI All provinces represented except PEI, top 5: ON, PQ, BC, AB, MB Courtesy of Betsy Sears, ExamOne 41

42 Unintended consequences: summary 42 42

43 Summary No magic bullet for chronic pain treatment Legitimate manufacture and prescribing fuel the opioid overdose epidemic Tighter prescribing guidelines and legislation restrict (previous easy) access Abuse deterrent opioid formulations promoted as safer (yet more costly) alternative may not address the actual problem Heroin, in purer form, has emerged as a cheaper alternative to opioids; rate of overdose deaths involving heroin has more than tripled in past 5 years: Illicitly manufactured fentanyl (IMF) has emerged as public health threat, commonly mixed with or sold as heroin; fentanyl deaths more than doubled in 1 year Marijuana, a weak analgesic, still need to weed out the risk Synthetic highs, new psychoactive substances, are another topic.. Drug overdose deaths are increasing while perceptions of harm vary and decriminalization trends continue 43

44 Underwriting risk assessment 44

45 Case: Better, neutral or worse risk? a. Pain control with regular exercise, single long-acting opioid b. Newly developed mild depression well controlled on low-dose SSRI c. Fentanyl patch just added d. Daily morphine equivalent dose of long-acting opioid well under 100mg/day e. Current Rx just replaced with methadone, also alprazolam, random drug screen shows oxycodone f. Current Rx replaced last year with medical marijuana and now stable, was vaping but switched to smoking Case: 49 year old male, factory worker, complex back pain with significant imaging abnormalities, APS mismatch with description on requisition but apparently no missed work. Stable Rx for >5 years: oxycodone /acetaminophen (Percocet) 10/325 mg 1-3 daily; fentanyl patch 75 mg q72 hours; zolpidem (Ambien) 10 mg nightly. CV risks well controlled, no alcohol or substance concerns 45

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