Traci C. Green, PhD, MScAssistant Professor of Emergency Medicine & EpidemiologyThe Warren Alpert School of Medicine at Brown University, Rhode Island Hospital

The following personal financial relationships with commercial interests relevant to this presentation existed during the past 12 months: Employment at Inflexxion, Inc.

My presentation will include discussion of “off-label” use of the following: Naloxone is FDA approved as an opioid antagonist Naloxone delivered as an intranasal spray with a mucosal

atomizer device has not been FDA approved and is off label use

Funding: CDC National Center for Injury Prevention and Control, 5R21CE001846-02 and 1R21CE002165-01; National Institute on Drug Abuse, 1R21DA029201-02A1

define the scope of national & state-level epidemiologic trends in prescription opioid abuse & overdose

identify factors influencing unintentional opioid poisoning using the Haddon Matrix

conceptualize a community based participatory research approach for understanding unintentional opioid poisonings in the community

describe community-based interventions for reduction of opioid overdose

More poisoning deaths involve prescription opioids than heroin, other illicit drugs

CDC has declared this an epidemic

Source: http://www.cdc.gov/nchs/data/databriefs/db81.htm

Olshansky et al., Health Affairs 2012

OxycodoneOxyContinPercodanPercocet

HydrocodoneVicodin

HydromorphoneDilaudid

Heroin Morphine Codeine Methadone Fentanyl

Availability, access, & potency of prescription opioids is unprecedented

Young people (Partnership for Drug-Free America, 2005)

College students (McCabe et al., 2005)

Elderly (SAMHSA, 2005)

Women (Manchikanti,2006; Green et al., 2008)

Chronic pain patients (Butler et al., 2004, 2008; Passik et al.,2006)

Street drug users (Davis & Johnson, 2008) Exhibits geographic patterns: greater in rural

areas, also seen among street-based users in large cities (Paulozzi et al., 2009; Brownstein et al., 2009)

Difficult to summarize & contrast these disparate groups, Let alone plan effective interventions

Class 1Use as

prescribedN=4,973

Class 2Prescribed misusersN=7,079

Class 3Medically healthy

abusersN=9,420

Class 4Illicit usersN=4,842

Class Prevalence 18.9% 26.9% 35.8% 18.4%

Indicators: ‘YES response to the following

Nonmedical use of Short acting prescription opioid

0.0761 0.7545 0.7512 0.8161Nonmedical use of Long acting prescription opioid

0.0031 0.4682 0.5091 0.9236Use by non-indicated route of administration 0.0111 0.2430 0.3374 0.9089Illicit source (i.e., not one’s own, single physician)

0.0005 0.4773 0.8816 0.9994Has a current chronic medical health problem/ pain problem

1.00 0.9706 0.5138 0.4346Takes prescribed medication for a medical problem/ Receives help for a medical problem, past 30 days

0.9485 0.8863 0.6068 0.4859

Pinpoint pupilsRespiratory depression (shallow/no breathing)Blue or grayish lips/fingernailsNo response to stimulusGurgling/ heavy wheezing or snoring sound

Occurs over 1-3 hours - the stereotype “needle in the arm” death is rare (15%)

Opioids repress the urge to breathe, decrease the body’s/brain’s response to carbon dioxide, leading to respiratory depression (decrease rate of breathing) and death

Drug overdose death rates by state per 100,000 people (2008)

Risk Factors for Unintentional Opioid Poisoning

Change in TOLERANCE using ALONE, by oneself MIXING opioids with other central nervous

system depressing substances (alcohol, benzodiazepines)

ILLNESS

(Sporer 2007, Binswanger 2007, Green 2012)

Method for conceptualizing injuryPre-event Event Post-eventTackle problems identified with each

factor during each phase

HOST

AGENT ENVIRONMENT

TIME + + =

2-year CDC funded project Collaborations with state medical examiners,

departments of health, consumer safety, mental health & addiction services, corrections

4-part study: Forensic case review, inter-agency data linkage (ME,PMP, DOC, SA/MH agencies), provider & pharmacist surveys, & community based rapid assessment field study in heavily affected cities

Rhode Island had the highest rate of past month illicit drug use in the nation among people 12 or older, according to national surveys conducted in 2008,2009, & 2010

5.93% of Rhode Islanders 12 or older report non-medical use of opioids, ranking 7th in the nation

Nationally: 4.9%Drug poisonings outrank motor vehicle

crashes as leading cause of injury death, since 2005

Sources: National Survey on Drug Use and Health, SAMHSA 2010, 2011, 2012; CDC WISQARS 2012

Green TC & Donnelly E. Preventable Death: Accidental Drug Overdose in Rhode Island. RI Med Health, Nov 2011

0

2

4

6

8

10

12

14

16

18

2005 2006 2007 2008 2009

Ag

e-ad

just

ed R

ate

per

100

,000

Poisoning*

Falls*

Motor Vehicle*

Suicide

Assault

Data Source: 2005 to 2009 Rhode Island Vital Record Death Data, Rhode Island Department of Health, Center for Health Data and Analysis.1Injury was listed as primary cause of death.2Age-adjusted to the year 2000 U.S. standard population

*Unintentional

50

100

150

200

250

300

1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007

Coun

t

Not opioid involved

Polyopioid

Methadone only

Single prescription opioids other than methadone

Heroin only

TC Green, LE Grau, HW Carver, M Kinzly, R Heimer. Epidemiologic and geographic trends in fatal opioid intoxications in Connecticut, USA: 1997-2007. Drug and Alcohol Dependence (2011).

Since 2005, leading cause of adult injury death, more than car crashes, fire, firearms deaths

Ethnographic tool, used widely in public health: HIV/AIDS

Investigate who, what, when, where, & why abuse/ deaths occurring

Suggest ways to intervene locally Two, 10-person Community Advisory Boards

Data collection over 12-week period Review publicly available data, media, online Existing local data sources (ambulance run data) 143 Key informant interviews 52 Brief surveys

• Two-thirds involved a prescription opioid

• Deaths occur among 35-54 age range, primarily non-Hispanic Whites, increasingly female, die at home

• Involve other pharmaceuticals: anti-depressants, sedatives/hypnotics

Drug &/or alcohol abuse/dependence, SA/MH treatment, domestic violence, past suicide attempts, previous overdose, incarceration, other chronic diseases or conditions (diabetes, obesity, back problems, chronic pain), recent acute events-surgery, work injury

Availability, accessibility of pain pills Endemic opioid problem Proliferation of pills in the home, community Age distribution “Complicated” patient Constrained & isolated drug treatment

resources Poor awareness of overdose risk, recognition Stigma of addiction, chronic pain care, pill use Fear of police, calling 911

Calling 911:

• Delay or don’t call 911– Want to protect

script doctor, fear of getting into trouble, stigma of drug use, they/ others have record

– Failure to recognize overdose symptoms

CDC ONDCP FDA Key Concerns

PRIMARY PREVENTION

Use PMPs, insurance to combat “dr. shopping”

Tracking, monitoring: operational PMPs, inter-state data sharing

Dr. shoppers: diverting or seeking help? How used? Access to pain care? Effectiveness? Overdose risk?

Legislation/enforcement of pill mill laws, Rx fraud

Target “unscrupulous” health professionals, pill mills, dr shopping

Swift opioid supply changes: unintended consequences? Effectiveness?

EBM, CMEs to improve safer prescribing*complex pain, pain-SA hx

Mandatory education for controlled substance prescribers

REMS, voluntary provider education

Education necessary but not sufficient

SECONDARY & TERTIARY PREVENTION

Distribution of naloxone to laypersons, 1st responders

Distribution of naloxone to laypersons

Moral hazard, “message”?

MAT: suboxone, methadone

Cost, readiness

Patients, parents education

Target? Necessary but not sufficient

Medication ‘take-backs’ / drop boxes

Effectiveness?; stigma

ADFs Unintended consequences: heroin, riskier use

Most use PMP reports to screen for abuse, complement patient care

When concerned about “dr. shopping”/diversion, PMP users significantly more likely than non-users to: Screen for drug abuse, conduct urine screens,

refer to another provider, refer to substance abuse treatment

Revisit pain treatment agreements Less likely to do nothing (ignore it) Fewer calls to law enforcement to intervene

Indirect not direct influence on overdose risk

Green et al., How Does Use of a Prescription Monitoring Program Change Medical Practice?Pain Medicine in press

MANY OPIOID OVERDOSES ARE PREVENTABLE

Prevention: Alter demand, supply, & harm

Interventions Recommendations

Demand • Prescriber Toolkit• Clinician Prescription

Monitoring Program Resources

• Targeted Medical Education

• Public Awareness Campaign

•Prescriber mandates•Expanded treatment (especially medication assisted treatment)•Addiction medicine residency•Local recovery center

Supply • Prescriber Toolkit• Clinician Prescription

Monitoring Program Resources

• Targeted Medical Education

• Medication Dropbox at Police Station

•Prescriber mandates•Addiction medicine residency

Harm •Naloxone Distribution•First Responder Prevention•Good Samaritan law

Structural

•Coordinate cross-agency response•Sponsor multi-agency meeting•Local Task Force involvement

Activities

Demand

Supply

Harm

Structural

Developed safer prescribing materials for RI, CT on Poison control website, Dept of Health, PMP; mailings to local providersCreated, printed, distributed English, Spanish overdose awareness posters for treatment centers, community organizations, clinics; wallet cards

Medication drop boxes installed in one study site

Targeted continuing medical education on safer prescribing + overdose for study area health professionals

Medication assisted therapy (MMT, Suboxone) expanded to two study sites

Activities

Demand

Supply

Harm

Structural

Developed safer prescribing materials for RI, CT on Poison control website, Dept of Health, PMP; mailings to local providersCreated, printed, distributed English, Spanish overdose awareness posters for treatment centers, community organizations, clinics; wallet cards

Medication drop boxes installed in one study site

Targeted continuing medical education on safer prescribing + overdose for study area health professionals

RI, CT Good Samaritan, Naloxone laws enacted, dissemination strategy

Medication assisted therapy (MMT, Suboxone) expanded to two study sites

Prescribing naloxone As of Aug 1, 2012, 8 states amended laws to

make it easier for health professionals to provide naloxone & for lay administrators to use it without fear of legal repercussions (NM, NY, IL, WA, CA, RI, CT and MA)

Good Samaritan laws to encourage calling 9-1-1 As of Oct 1, 2012, exist in 10 states (NM, WA, NY,

RI, CT, IL, CO, FL, MA and CA)

Activities

Demand

Supply

Harm

Structural

Developed safer prescribing materials for RI, CT on Poison control website, Dept of Health, PMP; mailings to local providersCreated, printed, distributed English, Spanish overdose awareness posters for treatment centers, community organizations, clinics; wallet cards

Medication drop boxes installed in one study site

Naloxone “train the trainer” pilots in CT and RI for 7 SA tx programs, MMT, recovery centers

Targeted continuing medical education on safer prescribing + overdose for study area health professionals

RI, CT Good Samaritan, Naloxone laws enacted, dissemination strategy

Medication assisted therapy (MMT, Suboxone) expanded to two study sites

Reverses opioid effects, restores breathing Not scheduled, not controlled, not abuseable Must be prescribed Works only on opioids (heroin, methadone, pain pills) Has no effect unless opioids are present Standard antidote used by EMS to diagnosis &

treat respiratory depression that causes overdose

Can be administered by laypeople, with training

Since 1996, community-based programs operating overdose education and naloxone programs In the last 15 years:

188 local programs, 15 US states, DC 10,171 drug overdose reversals w/naloxone 53,032 people trained and given naloxone RI: 177 trainings through community-based

organization pilot CT: 1 MMT, underground programs with

limited distribution MA program trained >15,000 community lay

people; >1,500 reversals. Protective effects seen with community saturation (Walley et al., under review)

One-to-one Provider-patient: Prescribe naloxone to patients

at high risk of opioid overdose

One-to-many Standing order (state, institution) Designate prescriber proxy Collaborative Pharmacy Practice Model (flu vaccine)

 ”Drug prevention—especially overdose prevention—is a critical piece of our mission.”

“Naloxone is a tool of overdose intervention, and once used, can become a critical link to substance abuse treatment—a tool for long-term overdose prevention.”

Patients: with history or suspected history of substance

abuse treated for opioid poisoning or intoxication at ED beginning Methadone or Buprenorphine therapy

for addiction with higher-dose opioid prescriptions (>50 mg

morphine equivalent/day) rotated from one prescription opioid to another with opioid prescriptions and:

▪ Benzodiazepine prescription▪ Anti-depressant prescription▪ Smoking, COPD, asthma, or other respiratory illness▪ Renal dysfunction, hepatic illness, cardiac disease, HIV/AIDS▪ Concurrent alcohol use

Activities

Demand

Supply

Harm

Structural

Developed safer prescribing materials for RI, CT on Poison control website, Dept of Health, PMPCreated, printed, distributed English, Spanish overdose awareness posters for treatment centers, community organizations, clinics; wallet cards

RI adopts Poisoning as 1 of 5 priority areas for CDC injury prevention planning grant; CT DMHAS adopts naloxone as “Good Clinical Practice”

Medication drop boxes installed in one study site

Naloxone “train the trainer” pilots in CT and RI for 7 SA tx programs, MMT, recovery centers

Targeted continuing medical education on safer prescribing for study area health professionals

RI Collaborative Pharmacy Practice Agreement for naloxone adopted by Pharmacy Board

RI, CT Good Samaritan, Naloxone laws enacted, dissemination strategy

Naloxone Summit: Strategic Planning to improve naloxone access in RI

Medication assisted therapy (MMT, Suboxone) expanded to two study sites

129 times more likely to die of drug overdose during first 2 weeks following release

Tolerance altered by abstinence; physical isolation (using alone)

Since 2005, RI pilot trained 1000’s prisoners, refer to community program for naloxone upon release

<20 have ever presented for take-home naloxone Similar outcomes in other locations, even with financial incentives

R21: NIDA grant (PI: Rich, Co-I: Green) started 4/11

19-minute overdose prevention & response DVD Conceptual model: Social learning theory, peer stories Prisoner-specific, highlighting unique risk & circumstances Rescue breathing, naloxone (IM, IN)

administration Literacy challenges

N=125 soon-to-be-released prisoners: opioid users or likely to bearound opioid users post-release Naloxone mailed to known address or met at

release

Activities

Demand

Supply

Harm

Structural

Developed safer prescribing materials for RI, CT on Poison control website, Dept of Health, PMPCreated, printed, distributed English, Spanish overdose awareness posters for treatment centers, community organizations, clinics; wallet cards

RI adopts Poisoning as one of 5 priority areas for CDC injury prevention planning grant; CT DMHAS adopts naloxone as “Good Clinical Practice”

Medication drop boxes installed in one study site

Naloxone “train the trainer” pilots in CT and RI for 7 SA tx programs, MMT, recovery centers

Targeted continuing medical education on safer prescribing for study area health professionals

RI Collaborative Pharmacy Practice Agreement for naloxone adopted by Pharmacy Board

RI, CT Good Samaritan, Naloxone laws enacted, dissemination strategy

Naloxone Summit: Strategic Planning to improve naloxone access in RI

Medication assisted therapy (MMT, Suboxone) expanded to two study sites

RI Department of Correction adopts overdose prevention as standard pre-release health education topic

Safe prescribing

Package inserts

Provider education

Prescription monitoring

C1 Use as prescribed

C2 Prescribed misusers

Overdose prevention counseling

BMI

PMP-based intervention

Psychosocialweb-based

interventions, social support

Interdisciplinary pain

management

Targeted overdose

prevention counseling &

response (detox, EDs, AA groups)

SBIRT ED, primary care

Poison Control Center-based interventions

C3 Medically healthyabusers

Availability & access to Medication-assisted substance abuse treatment

C4 Illicit users

Targeted overdose prevention

counseling & response (SEPs,

detox, prison)

SEP, POS syringe access

Police-based interventions

Law/policy reform

SBIRT pediatric

Motor vehicle safety: A 20th century public health achievement

Motor-Vehicle–Related Deaths Per Million Vehicle Miles Traveled (VMT) and Annual VMT, by Year—United States, 1925-1997 Source: US Department of Health and Human Services

Traci.c.green@gmail.com (401) 444 3845

TC Green, R Black, JM Grimes-Serrano, SH Budman, SF Butler. Typologies of Prescription Opioid Use in a Large Sample of Adults Assessed for Substance Abuse Treatment. PLoS ONE (6(11): e27244). http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0027244

TC Green, MR Mann, SE Bowman, N Zaller, X Soto, J Gadea, C Cordy, P Kelly, PD Friedmann. How does use of a prescription monitoring program change clinical practice? Pain Medicine (in press)

TC Green, S McGowan, M Yokell, ER Pouget, JD Rich. HIV Infection and Risk of Overdose: A Systematic Review and Meta-Analysis. AIDS 2012 Feb 20;26(4):403-17.

TC Green, EF Donnelly. Preventable death: Accidental drug overdose in Rhode Island. Medicine & Health Rhode Island. 2011; 24(11): 341-343.

TC Green, N Zaller, S Bowman, JD Rich, PD Friedmann. Revisiting Paulozzi et al.’s “Prescription Drug Monitoring Programs and Death Rates from Drug Overdose”. Letter. Pain Medicine 2011; 12 (6): 982-985.

M Yokell, TC Green, S Bowman, M McKenzie, JD Rich. Opioid overdose prevention and naloxone distribution in Rhode Island. Medicine & Health Rhode Island. 2011; 94 (8): 240-242.

TC Green, LE Grau, HW Carver, M Kinzly, R Heimer. Epidemiologic and geographic trends in fatal opioid intoxications in Connecticut, USA: 1997-2007. Drug and Alcohol Dependence 2011 Jun 1;115(3):221-8.

JS Brownstein, TC Green, T Cassidy, SF Butler. Geographic Information Systems and Pharmacoepidemiology: Using spatial cluster detection to monitor local patterns of prescription opioid abuse. Pharmacoepidemiology and Drug Safety 2010; 19(6):627-37.

TC Green, J Grimes-Serrano, A Licari, SH Budman, SF Butler. Women who abuse prescription opioids: Findings from the National Addictions Vigilance Intervention and Prevention Program (NAVIPPRO™). Drug and Alcohol Dependence 2009.

TC Green, LE Grau, KN Blinnikova, M Torban, E Krupitsky, R Ilyuk, A Kozlov, R Heimer. Social and structural aspects of the overdose risk environment in St. Petersburg, Russia. International Journal of Drug Policy, Special Issue: Drug Use and Risk Environments 2009.

Staying Alive on the Outside video available at prisonerhealth.org &http://www.youtube.com/watch?v=_QwgxWO4q38&feature=player_embedded

 21-28.8-3. Authority to administer opioid antagonists – Release from liability. – (a) A person may administer an opioid antagonist to another person if: (1) He or she, in good faith, believes the other person is experiencing a drug overdose; and (2) He or she acts with reasonable care in administering the drug to the other person. (b) A person who administers an opioid antagonist to another person pursuant to this section shall not be subject to civil liability or criminal prosecution as a result of the administration of the drug. 

 

21-28.8-4. Emergency overdose care – Immunity from legal repercussions. 1 – (a) Any person who, in good faith, without malice and in the absence of evidence of an intent to defraud, seeks medical assistance for someone experiencing a drug overdose or other drug-related medical emergency shall not be charged or prosecuted for any crime under RIGL 21-28 or 21-28.5, except for a crime involving the manufacture or possession with the intent to manufacture a controlled substance or possession with intent to deliver a controlled substance, if the evidence for the charge was gained as a result of the seeking of medical assistance.(b) A person who experiences a drug overdose or other drug-related medical emergency and is in need of medical assistance shall not be charged or prosecuted for any crime under RIGL 21-28 or 21-28.5, except for a crime involving the manufacture or possession with the intent to manufacture a controlled substance or possession with intent to deliver a controlled substance, if the evidence for the charge was gained as a result of the overdose and the need for medical assistance. (c) The act of providing first aid or other medical assistance to someone who is experiencing a drug overdose or other drug-related medical emergency may be used as a mitigating factor in a criminal prosecution pursuant to the controlled substances act.