Safe and Effective Opioid Prescribing in the Internet Age Nathaniel Katz, MD, MS Tufts University School of Medicine March 6, 2007 The dogmas of our quiet past are inadequate to our stormy present. Abraham Lincoln State of the Union Address December 8, 1863 Opioid Dogmas: Historical Timeline Morphine and Opioids PreservedEbers poppypapyrus: Opioids opioids shouldindicated be Harrison Opioids for Opioids
forAct: painhave hypodermic rarely needle benefits seeds and indicated pods in for aavoided plethora due to ailments: opioids highly & numerous addictive era ofcomplications: Neolithic dwellingsofin dependence: ailments Erasistratus addictive when Galen herald newafter all: increase pharmacotherapy targeted Switzerland of Alexandria
prescribed forprescribing pain opioid availability 4000 1500 500 BC 300 0 120 1860s 1920s AD 1990s 2007
Opioid Efficacy in Chronic Pain About 30 published placebo-controlled RCTs of opioids in chronic noncancer pain All opioids tested work All pain syndromes tested are relieved Opioids more efficacious than comparators Case series show long-term safety and efficacy in a subgroup No long-term prospective studies Opioid Tolerance It is important to note that while the concept of opioid analgesic tolerance has become accepted clinical dogma, development of opioid analgesic tolerance has never been truly assessed in a prospective, long-term controlled fashion in chronic non-cancer pain patients.
Galer B, et al, Pain, 2005 Prospective study of elicited opioid side effects Jamison RN, et al, Spine, 1998 Opioid hypogonadism: the major toxicity of long-term opioid therapy Daniell H, J Pain, 2002 Rajagopal A, J Pain Sympt Manage, 2003
20 cancer survivors on opioids vs. 20 not on opioids 90% of opioid pts had hypogonadism vs. 40% controls Sexual function, mood, fatigue, and QOL reduced Katz N (unpublished) 20 disease-free cancer survivors on opioids Median testosterone 140 ng/ml (241-827) Rajagopal A, Pain, 2004 54 pts on opioid tx compared to 27 controls 74% of pts had subnormal total testo levels 25 pain pts on chronic opioids vs. 198 healthy controls Testosterone subnormal in 68% of controls All commonly used opioids implicated including methadone and TD fentanyl Six studies show high prevalence of hypogonadism on IT opioids
At least four studies of methadone maintenance show hypogonadism with various control groups The Dogma of Distinct Populations Good pain patients who rarely become addicted to prescription opioids Bad people (nonpatients) who somehow obtain opioids and become addicted The Dogma of Distinct Populations Patients who use opioids responsibly over time PTS WITH CO-MORBID PAIN AND SUBSTANCE ABUSE Non-patients who obtain opioids and
become addicted Co-Morbid Chronic Pain and Substance Abuse are Highly Prevalent 10-30% of adult population has chronic pain ~10% background rate of substance abuse 1.5-2 million adults have opioid addiction 30-60% of opioid addicts have chronic pain 2-9 million in US with pain & SUD 0.6-1.2 million with pain and opioid addiction 6-8 million in US on long-term opioids for pain
20% positive urine tox 1 million in US on opioid tx with pos. urine tox Potter et al. Drug Alcohol Depend. 2004;76:213; Jamison et al. J Pain Symptom Manage. 2000;19:53; SAMHSA 2006; IMS NPA. Dogma: Patients prescribed opioids for pain do not develop euphoria Figure 1: Mean Score of the Modified 46 Item ARCI MBG Subscale between Cases and Controls 10 Score 9 8 8.70* p=<.001 n=40 7 6 5
4 2.55* p=<.001 3 2 1 0 Case * p=<.001 Control Group Katz N, et al, unpublished, 2007 Prospective studies on the incidence of prescription opioid abuse among pain patients Adams E, et al, J Pain Sympt Manage, 2006
Prospective RCT, N=11,352 Abuse Index positive in: 2.5% for NSAIDs, 2.7% for tramadol, and 4.9% for hydrocodone Ives TJ, BMC Health Svcs Res, 2006 Prospective observational study, N=196 32% incidence of opioid misuse Volume of Diverted Opioids Study Opioids dispensed per year in US (IMS, 20022003) Non-medical users in last year (NSDUH) 190 million prescriptions 9.4 billion doses
11 million people 430 million non-medical use days Minimum of 430 million abused doses (1 dose/day) Katz N, Castor A, Birnbaum H. Submitted, 2006 Figure 1. Percentages of Reported Method** of Obtaining Prescription Pain Relievers for Their Most Recent Nonmedical Use in the Past Year among Persons Aged 18 to 25: 2005 NSDUH RADARS Diversion Study, Cicero T, et al, 2006 Rx Abuse 80.00% Dealer Doctor Prescription Friend or Relative Forged Prescription or Stolen Internet 70.00% 60.00% 50.00% 40.00%
30.00% 20.00% 10.00% 0.00% Less than 21 21 to 30 31 to 40 41 to 50 51+ Source of Drugs (NAVIPPRO) 100% 90% 80% 70% 60% 50% 40% 30% 20% 10%
0% Lortab Own Prescription Multiple Drs Percocet Internet OxyContin Family/Friends Dealer All Products Forgery Stolen Other Source Inflexxion, Inc., 2006, data on file Estimated Percentage of Schedule II Opioid Prescriptions Dispensed to Individuals Showing Questionable Activity* by Fiscal Year 6 Percentage 5 4 3
2.5 million dosage units 2 1 0 96 97 98 99 00 01 02 03 04
Fiscal Year *Questionable Activity = obtained Schedule II opioid prescriptions from >4 pharmacies and >4 physicians during the specified year 05 Role of the internet Negative Source of diverted prescription opioids Encouragement of abuse Sharing of extraction recipes Positive Harm reduction Opportunities for surveillance Opportunities for studies
Sample Internet Recipe Quantitative Internet Surveillance Three internet message boards surveilled over six months Development and validation of rating system for drug-related posts N = 48,293 internet posts manually harvested Webcrawler currently continuously monitoring prescription opioid abuse mentions Butler S, et al, APS Poster, 2006 Quantitative Internet Surveillance Figure 4. Total Mentions of Target Drugs by 1000 Month 900 800 700
600 500 400 300 200 100 0 February March April OxyContin Mentions May Vicodin Mentions June Kadian Mentions July Internet survey of prescription opioid abuse, N=1033 100
80 50% 60 45% 40% 40 35% 30% 20 25% 20% 0 15% 10% -20 OxyContin Oxycodone ER
5% Vicodin Hydrocodone Kadian Morphine ER 0% l l T n e x R in ne ero tiq on tin o ne A S di ny -I te c
n o nt o a S u d F t A d o o d c b i c M a o C la em en V XY th
al Su xy xyc D F S O e P O M r M O o c ri IR e en XY G O Katz N, et al, APS poster, 2007 Safe opioid prescribing in the Internet Era
Triage Structured monitoring and documentation for all patients Single prescriber and pharmacy Treatment agreements Secure medication storage Urine toxicology
PMP data Conviction/DUI data Significant other interviews Tamper-proof prescriptions Brief intervention and referral Exit strategy Abuse-deterrent opioids Research agenda for safe opioid prescribing: the anti-dogma Large prospective study of opioid efficacy and incidence of and risk factors for prescription opioid abuse Validation of treatment matching of pain patients by risk category Validation of exit strategies
Dissemination and validation of simple prescribing guidelines Validation of guidelines for interpretation of PMP data Validation of screening and assessment tools for POA Skill development training for SBIRT Training of pain physicians on addiction medicine Development of consumer education materials regarding responsibilities with opioids Clinical trials of treatment for patients with co-morbid pain and substance abuse Colleagues Mass DPH Grant Carrow Adele Audet Lee Panas MeeLee Kim John Eadie Analgesic Research Jessica DerMarderosian Gajanan Bhat Cheryl Murphy McLean Hospital Roger Weiss Jennifer Sharpe Potter David Borsook Inflexxion, Inc. Stephen Butler
Simon Budman Kathrine Fernandez Christine Benoit Corey Bieber Synne Venuti Tufts Program in Opioid Risk Mgt. Rosemarie Curran Marc Edelstein Sonal Jhaveri Brigham & Womens Hospital Robert Jamison Discussion
