Prescription Overdose Deaths Prescription Overdose Deaths in Rural Virginiain Rural Virginia

Martha J Wunsch MD FAAP FASAMMartha J Wunsch MD FAAP FASAM

Associate Professor, Virginia Associate Professor, Virginia College of Osteopathic MedicineCollege of Osteopathic Medicine

““Time to Team Up!”Time to Team Up!”November 16, 2007November 16, 2007

Virginia PMP & Virginia Board of MedicineVirginia PMP & Virginia Board of Medicine

Learning Objectives

• Discuss the literature addressing rural prescription drug abuse

• Describe those decedents for whom prescription medications were a direct or contributing cause of death in Southwestern Virginia.

• Discuss Universal Precautions in the treatment of Pain

Literature Rural Rx Drug Abuse

• 1525 Felony Probationers 2001-20041

– Rural probationers were 5X more likely to have abused prescription opioids

• 233 Treatment Professionals Key Informants (RADARS)2

– Geographic pockets of abuse of hydrocodone and oxycodone

– Predominantly in very small urban, suburban, rural areas.

1Havens et al. Am J Drug Alcohol Abuse. 2007;33(2):309-17

2Cicero et al. Pharmacoepidemiol Drug Saf. 2007 Aug;16(8):827-40

Literature Rural Rx Drug Abuse

• 233 Probationers and Prisoners SW Va 3

– Modified/Augmented ASI (2002-2004)– 40% OxyContin Addiction

• Younger, less likely to be married• More likely to be female• More likely to abuse BZD, Methadone, cocaine, heroin.

• OxyContin Use Abuse and Diversion in SW Va4

– 50 OxyContin Addiction, 50 Prisoners, 34 Pain Patients : ASI, DSM IV, questionnaire

– Demographics, Psychiatric Hx, Family not useful– SA history and POMI differentiated.

3. Wunsch et al. Journal of Addictive Disease. 26(4): 15-22.

4. Wunsch et al., under review Journal of Opioid Management.

**Opioids as a direct or contributing cause of deathOpioids as a direct or contributing cause of death

Year Drug Deaths

Opioid Related Deaths*

Oxycodone Methadone Fentanyl Hydrocodone MSO4

1997 67 ? 1 4 0 6 12

1998 69 8 3 6 0 12 7

1999 84 25 18 12 0 8 11

2000 101 36 19 22 1 10 17

2001 164 95 41 49 9 34 13

Medical Examiner Cases SW Va

Drug and Rx Opioid Deaths

0

50

100

150

200

250

300

1998 1999 2000 2001 2002 2003 2004 2005

Year

Num

ber

of D

eath

s

Drug Deaths

Opioid Deaths

Overall Goal*

“The overall goal of this study is to characterize Medical Examiner cases where prescription medications are identified as a direct or contributing case of death in a rural area of Virginia”

*National Institute of Drug Abuse National Institute of Drug Abuse RO3 DA019047-01A1

Methods: In depth review of Medical Examiner Files 1997-2003

• Autopsy Results

• Death Certificates

• Death Scene Investigations

• Police Reports

• Toxicology Reports

• Physician Notes

• Hospital Records ( ER, Inpatient, Psych)

Data from Western District

Prevalence of Drug-related Fatalities

Western VA U.S.

Male 23.3 per 100K 12.9 per 100K

Female 11.8 per 100K 7.0 per 100K

• 893 drug-related deaths (1997-2003) in Western Virginia

• 686 (76.8%) involved opioids

Demographics of Opioid DeathsN=686 (1997-2003)

• Gender– 64.9% Male ; 35.1% Female

• Median Age of sample– 39.7 years

• Males 38.6 years• Females 41.4 years

• Race– 95.9% White ; 3.9% African American ;

0.4% Native American; 0.1% Asian

Employment

• Employment Status

– Working 48.1%– Disabled 25.4% – Unemployed 12.9% – Unknown 12.1%– Retired 1.5%

• Occupation

– Homemaker 11.5%– Construction 10.2%– Mining Labor 4.2%– Mfg Labor 7.4%– Other Labor 9.0%

Marital Status

Overall Male Female

Ever Married 70.6% 63.1% 83.5%

Single 25.5% 31.9% 13.9%p<.01

Opioid Deaths

• Of total 893 deaths, opioids were a direct or contributing cause of death in 686.

• Prevalent opioids listed as a cause of death:

Methadone 249

Hydrocodone 160

Oxycodone 160

Fentanyl 45

Heroin 19

>1 Opioid (Polydrug)(present on toxicology)

252

Opioid Mortality: Manner of Death

Overall Male Female

Accident 78.9 % 84.3% 69.2%

Suicide 18.1% 12.8% 27.9%

Other 0.8% 0.9% 0.8%

Unknown 2.0% 2.0% 2.1%

p<.001

Other Drugs Present(Identified on Toxicology)

Tobacco* 29.3%

Cocaine 12.1%

Alcohol 27.4%

Cocaethylene 2.0%

Methamphetamine 0.4%

Any Anti-depressant 44.6%

Any Benzodiazepine 45.9%

*from History

Age & Gender Distribution

Male Female

Under 35 169

38.0%

52

21.6%

35 or Older 276

62.0%

189

78.4%

• Deaths among older people predominate (consistent with other studies of Rx drug deaths)

• Most pronounced among women

Prescription Drug Mortality

• CDC Injury Study 1990-2001 (11 states)4

– Poisonings increased average of 145% nationwide.

– Highest rates among 35-54 year olds

• New Dawn 2003 (6 states)5

– Multiple drugs involved in opioid related deaths

– Highest death rates were 35-54 year olds in 5 of 6 states.

4MMWR Weekly. 2004;53(11):233-238. 4SAMHSA DAWN Report: Opiate-Related Drug Misuse Death in Six States: 20035Substance Abuse and Mental Health Services Administration. The New DAWN Report: Opiate-Related Drug Misuse Death in Six States: 2003; 2006, Issue 19.

Opioid Prescriptions and Pain

Decedents Holding Opioid Prescription

Male Female

Under 35 31.1% 34.0%

35 or Older 43.5% 54.5%

Decedents with History of Chronic Pain

Male Female

Under 35 24.5% 23.4%

35 or Older 38.4% 49.7%

Depression and Anxiety

Decedents with History of Depression

Male Female

Under 35 26.5% 44.7%

35 or Older 39.5% 52.9%

Decedents with History of Anxiety

Male Female

Under 35 15.2% 10.6%

35 or Older 15.6% 25.4%

Prescriptions for Related Drugs

Decedents with Prescription for Anti-depressant

Male Female

Under 35 19.2% 25.5%

35 or Older 26.1% 47.6%

Decedents with Prescription for Benzodiazepine

Male Female

Under 35 25.2% 36.2%

35 or Older 35.1% 50.3%

Disturbing Pattern

• Of female decedents with Rx for Opioid:– 68.6% hold Rx for Benzodiazepine– 61.2% hold Rx for Anti-depressant

• Of male decedents with Rx for Opioid:– 59.1% hold Rx for Benzodiazepine– 39.8% hold Rx for Anti-depressant

• Female decedents over 35 exhibit particularly high rates of co-morbidity of chronic pain, depression, and anxiety and hold prescriptions for multiple drugs including opioids, benzodiazepines, and anti-depressants

What about the cases where Methadone was identified on

toxicology?

The most commonly identified opioid in our cases

Methadone Mortality Demographics

• Gender– 75.2% Male ; 24.8% Female

• Race – 98% White ; 1.2% African American; .4 %

Asian• 45 % of decedents were prescribed an opioid

– 53% of these decedents were prescribed methadone

Age Group55 or Older35-5420-34Under 20

N >

0 A

NY

Met

had

on

e o

r M

etab

oly

tes

120

100

80

60

40

20

0

MaleFemale

Sex

Age Distribution of Cases

Co-Morbidity: Methadone Cases

• Chronic Pain 40%– 55 % have an antidepressant on toxicology – 55 % have a benzodiazepine on toxicology

• Anxiety Disorder 19%– 50% have an antidepressant on toxicology – 46% have a benzodiazepine on toxicology

• Depression 40%– 60% have an antidepressant on toxicology – 56% have a benzodiazepine on toxicology

Toxicology Results

• Opioids– 68% had only methadone present – 24% had methadone AND another opioid

present– 8% had methadone AND 2 or more opioids

present

Source of Methadone in 2004 Medical Examiner Drug Deaths

Melissa Weimer DOMartha Wunsch MD

Goal of the Project

• Describe methadone deaths in western Virginia from January 1, 2004 to December 31, 2004.

• Ascertain the probable source of methadone.

• Compare decedents for which methadone was– Prescribed in an opiate treatment programs – Prescribed for the treatment of pain– Procured illicitly.

“Subjects”

• Retrospective, population-based investigation of all medical examiner cases January 1, 2004-December 31, 2004.

• Subjects:– Accessed OCME computer database of deaths and

autopsies in 2004 where poisoning was the fatal agency.

– Identified cases where methadone detected in the serum toxicology.

– Selected cases were methadone was noted to be a direct or contributing cause of death.

Cases Definition

• Total Drug Deaths 2004– 204 Identified– 68 cases (33.5%)

• Methadone was identified as a direct or contributing cause of death AND toxicology was positive

• 7 excluded because they lived outside the PMP Pilot Study area (source unavailable)

– 61 Cases for study

Procedures• Review of case files and entry into

existing database*– Autopsy Results– Death Certificates– Death Scene Investigations– Police Reports– Toxicology Reports– Physician Notes– Hospital Records ( ER, Inpatient, Psych)

*National Institute of Drug Abuse National Institute of Drug Abuse RO3 DA019047-01A1

Demographic Characteristics

• 95% Caucasian

• 64% male

• 49% metropolitan residence

• 44% rural residence

• Age: Range 19-59; mean 35.8 years old

Case Characteristics• History of Drug Abuse 54%

– Intravenous Drug Use (autopsy)– Evidence death scene (drugs, syringes, straws)– Medical/Psychiatric History

• Addiction treatment• Overdose requiring hospitalization• Cocaine, cannabis, opioid abuse

• Cause of Death– Methadone sole agent 34%; Polydrug abuse 66%

Procedure

• Using the Virginia Prescription Monitoring Program identify decedents who were prescribed methadone for the treatment of pain*– Prescription misuse

• >1 physician Rx obtained simultaneously.• >1pharmacies used to fill Rx simultaneously.• >1 Rx filled in one month.

*Methadone can only be prescribed in a private office for the treatment of pain (Harrison Act, 1914)

Procedure

• Identify decedents ever enrolled in an opioid treatment program– Medical Examiners and Substance Abuse treatment

programs may communicate in death investigations without permission of next of kin (42 CFR Part 8)

– Contacted program directors to identify cases

• By exclusion, decedents identified as obtaining methadone illicitly

Results

Figure 1: Source of Methadone

62%13%

25%Unknown source

Prior or current MMT

Physician Prescription

Results

Physician Rx Methadone

Enrolled in Opiate Treatment Program

Unknown source

N (%) N (%) N (%) Cases 16 (26.2%) 8 (13.1%) 38 (62.3%) Age 21-51 21-49 19-59 Avg Age 42.4 29 34 Gender Male 9 (56.3%) 6 (75%) 25 (65.8%) Female 7 (43.7%) 2 (25%) 13 (34.2%)

Results Physician

Rx Methadone

Enrolled in Opiate Treatment Program

Unknown source

Race Caucasian 16 (100%) 8 (100%) 35 (92%) African-American

0 (0%) 0 (0%) 2 (5.3%)

Unknown 0 (0%) 0 (0%) 1 (2.6%) Residence Metropolitian 10 (62.5%) 2 (25%) 18 (47.4%) Micropolitan 0 (0%) 1 (12.5%) 3 (7.9%) Rural 6 (37.5%) 5 (62.5%) 17 (44.7%)

Results

Physician Rx Methadone

Enrolled in Opiate Treatment Program

Unknown source

Postmortem Methadone level

0.448mg/L 0.801mg/L 0.420 mg/L

Autopsy cause of death

Methadone only overdose

4 (25%) 4 (50%) 13 (34.2%)

Polysubstance overdose

12 (75%) 4 (50%) 25 (65.8%)

Results

Physician Rx Methadone

Enrolled in Opiate Treatment Program

Unknown source

Antidepressants present

8 (50.0%) 1 (12.5%) 4 (10.53%)

Benzodiazepines present

5 (31.3%) 6 (62.5%) 15 (39.5%)

Other opiates present 3 (18.8%) 2 (25%) 14 (36.8%) Ethanol present 4 (25%) 3 (37.5%) 5 (13.2%) Cocaine present 4 (25%) 0 (0%) 4 (10.5%)

Conclusions

• Minority of the cases were individuals who were enrolled in “methadone clinics”

• Majority of cases involved overdose with multiple substances

• Differences in those who were prescribed methadone for:– The treatment of pain– The treatment of opioid addiction

• Methadone: PK, metabolism, lethality

Treating Pain in midst of an “epidemic” of Prescription Drug Abuse

Suggested Reading:

Gourlay DL, Heit HA, Almahrezi A. Universal precautions in pain medicine: a rational approach to the treatment of chronic pain. Pain Medicine. 2005;6(2):107-12.

Universal Precautions

1. Make a Diagnosis with Appropriate Differential

2. Conduct a Psychological Assessment Including Risk of Addictive Disorders

3. Informed Consent

4. Treatment Agreement

5. Pre- and Post-Intervention Assessment of Pain Level and Function

Universal Precautions

6. Appropriate Trial of Opioid Therapy +/– Adjunctive Medication

7. Reassessment of Pain Score and Level of Function at each visit

8. Regularly Assess the “Four A’s” of Pain Medicine

9. Periodically Review Pain Diagnosis and Comorbid Conditions, Including Addictive Disorders

10. Documentation: careful and complete recording of the initial evaluation and at each follow up is both medically and legally indicated and in the best interest of all parties.

Literature

• Havens JR, Oser CB, Leukefeld CG, Webster JM, Martin SS, O'Connell DJ, Surratt HL, Inciardi JA. Differences in prevalence of prescription opiate misuse among rural and urban probationers. Am J Drug Alcohol Abuse. 2007;33(2):309-17.

• Cicero TJ, Surratt H, Inciardi JA, Munoz A. Relationship between therapeutic use and abuse of opioid analgesics in rural, suburban, and urban locations in the United States. Pharmacoepidemiol Drug Saf. 2007 Aug;16(8):827-40.

Literature Cited

• Paulozzi LJ, Budnitz DS, Xi Y. Increasing deaths from opioid analgesics in the United States. Pharmacoepidemiol Drug Saf. 2006 Sep;15(9):618-27

• Centers for Disease Control and Prevention. Unintentional and undetermined poisoning deaths-11 states, 1990-2001. MMWR Weekly. 2004;53(11):233-238.

• Substance Abuse and Mental Health Services Administration. The New DAWN Report: Opiate-Related Drug Misuse Death in Six States: 2003; 2006, Issue 19.

Literature Cited

• Wunsch MJ, Nakamoto K, Goswami A, Schnoll SH. Prescription Drug Abuse among Prisoners in Rural Southwestern Virginia. Journal of Addictive Disease. 26(4): 15-22.

• Wunsch MJ, Cropsey KL, Campbell E, Knisely JC. OxyContin® Use, Abuse, and Diversion in Three Populations in Southwestern Virginia. Under review Journal of Opioid Managment