# Presentation: 055544

## 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

- Preserved poppy seeds and pods in Neolithic dwellings in Switzerland

- 4000

- 1500

- Ebers papyrus: opioids indicated for a plethora of ailments

- Opioids should be avoided due to dependence: Erasistratus of Alexandria

- 500

- 300

- 120

- 1920s

- 1990s

- 2007

- BC

- 0

- AD

- Opioids indicated for numerous ailments: Galen

- 1860s

- Morphine and hypodermic needle herald new era of pharmacotherapy

- Harrison Act: opioids highly addictive when prescribed for pain

- Opioids for pain rarely addictive after all: increase opioid availability

- Opioids have benefits & complications: targeted prescribing

## 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

**Notes:**
But no long-term efficacy or safety data
Only a minority respond long-term
Only part of the pain is relieved.

## Opioid Tolerance

- Galer B, et al, Pain, 2005

- “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.”

## 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
- 54 pts on opioid tx compared to 27 controls
- 74% of pts had subnormal total testo levels
- Rajagopal A, J Pain Sympt Manage, 2003
- 20 disease-free cancer survivors on opioids
- Median testosterone 140 ng/ml (241-827)
- Rajagopal A, Pain, 2004
- 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- Katz N (unpublished)
- 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 (non-patients) who somehow obtain opioids and become addicted

## The Dogma of Distinct Populations

- Patients who use opioids responsibly over time

- Non-patients who obtain opioids and become addicted

**PTS WITH CO-MORBID PAIN AND SUBSTANCE ABUSE**

## Co-Morbid Chronic Pain and Substance Abuse are Highly Prevalent

- 10-30% of adult population has chronic pain
- ~10% background rate of substance abuse
- 2-9 million in US with pain & SUD
- 1.5-2 million adults have opioid addiction
- 30-60% of opioid addicts have chronic pain
- 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

- n=40

- 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, 2002- 2003)
- 190 million prescriptions
- 9.4 billion doses
- Non-medical users in last year (NSDUH)
- 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 

- 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

## Source of Drugs (NAVIPPRO)

**Lortab****®**

**Percocet****®**

**OxyContin****®**

**All Products**

**Own Prescription**

**Multiple Drs**

**Internet**

**Family/Friends**

**Dealer**

**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

***Questionable Activity = obtained Schedule II opioid prescriptions from **_**>**_**4 pharmacies and **_**>**_**4 physicians during the specified year**

**0**

**1**

**2**

**3**

**4**

**5**

**6**

**96**

**97**

**98**

**99**

**00**

**01**

**02**

**03**

**04**

**05**

**Fiscal Year**

**Percentage**

**Notes:**
Animate such that red stuff dissolves in on click.

## 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

## Internet survey of prescription opioid abuse, N=1033

- 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 & Women’s Hospital_
- Robert Jamison

## Discussion