1. APHA Overdose Workshop
Prescription Drug Abuse
Nicholas Reuter
Center for Substance Abuse Treatment
Substance Abuse Mental Health Services Administration
U.S. Department of Health & Human Services
APHA Overdose Workshop
November 10, 2010

2. No relationships to disclose
Nicholas Reuter
(1) The following personal financial relationships with commercial interests relevant to this presentation existed during the past 12 months:
No relationships to disclose

4. Overview Substance Abuse Trends in the U.S. Illicit Drugs
Prescription Drugs
Abuse
Availability
Mortality
Initiatives to Address Rx Drug Abuse
Dosing Guidelines
Prescriber/Consumer Education/Training

5. SAMHSA’s Strategic Initiatives
Prevention of Substance Abuse & Mental Illness
Trauma and Justice
Military Families – Active, Guard, Reserve, and Veteran
Health Reform
Housing and Homelessness
Jobs and the Economy
Health Information Technology for Behavioral Health Providers
Data Quality and Outcomes – Demonstrating Results

6. 2009 NSDUH Highlights
New National Survey Reveals shows the overall rate of current illicit drug use in the United States rose from 8.0 percent of the population aged 12 and older in 2008 to 8.7 percent in This rise in overall drug use was driven in large part by increases in marijuana use.
The nonmedical use of prescription drugs rose from 2.5 percent of the population in 2008 to 2.8 percent in 2009,
the number of methamphetamine users rose from 314,000 to 502,000 during that period
estimated number of past-month ecstasy users rose from 555,000 in 2008 to 760,000 in 2009
These results are a wake-up call to the nation,” said SAMHSA Administrator Pamela S. Hyde, J.D. “Our strategies of the past appear to have stalled out with generation ‘next.’ Parents and caregivers, teachers, coaches, faith and community leaders, must find credible new ways to communicate with our youth about the dangers of substance abuse.”

7. Results from the 2009 National Survey on Drug Use and Health (NSDUH)
Substance Abuse and Mental Health Services Administration
Fig
2.2
Past Month Use of Selected Illicit Drugs among Persons Aged 12 or Older:
Percent Using in Past Month
Illicit Drugs
Marijuana
Psycho-therapeutics
Cocaine
Hallucinogens
+ Difference between this estimate and the 2009 estimate is statistically significant at the .05 level. 7 7

8. Past Month Illicit Drug Use among Persons Aged 12 or Older: 2009
Fig
2.1
Results from the 2009 National Survey on Drug Use and Health (NSDUH)
Substance Abuse and Mental Health Services Administration
Past Month Illicit Drug Use among Persons Aged 12 or Older: 2009 1
(8.7%)
(6.6%)
(2.8%)
(0.7%)
(0.5%)
(0.2%)
(0.1%)
Numbers in Millions
1 Illicit Drugs include marijuana/hashish, cocaine (including crack), heroin, hallucinogens, inhalants, or prescription-type psychotherapeutics used nonmedically. 8 8

9. 3.1 Million Initiates of Illicit Drugs
Results from the 2009 National Survey on Drug Use and Health (NSDUH)
Substance Abuse and Mental Health Services Administration
Fig
5.1
First Specific Drug Associated with Initiation of Illicit Drug Use among Past Year Illicit Drug Initiates Aged 12 or Older: 2009
Pain Relievers (17.1%)
Inhalants (9.8%)
Tranquilizers (8.6%)
Marijuana (59.1%)
Hallucinogens (2.1%)
Stimulants (2.0%)
Sedatives (1.0%)
Cocaine (0.3%)
Heroin (0.1%)
3.1 Million Initiates of Illicit Drugs
Note: The percentages do not add to 100 percent due to rounding or because a small number of respondents initiated multiple drugs on the same day. The first specific drug refers to the one that was used on the occasion of first-time use of any illicit drug. 9 9

10. Results from the 2009 National Survey on Drug Use and Health (NSDUH)
Substance Abuse and Mental Health Services Administration
Fig
5.2
Past Year Initiates of Specific Illicit Drugs among Persons Aged 12 or Older: 2009
Numbers in Thousands
Marijuana
Pain Relievers
Tranquilizers
Ecstasy
Inhalants
Stimulants
Cocaine
LSD
Sedatives
Heroin
PCP
Note: The specific drug refers to the one that was used for the first time, regardless of whether it was the first drug used or not. 10 10

11. Pain Reliever Trends among Persons Aged 12 or Older: 2002 to 2009
Results from the 2009 National Survey on Drug Use and Health (NSDUH)
Substance Abuse and Mental Health Services Administration
Pain Reliever Trends among Persons Aged 12 or Older: to 2009
Numbers in Thousands
Past Month Users (+20%)
Dependence (+50%)
Treatment in Past Year (+100%)
+ Difference between this estimate and the 2009 estimate is statistically significant at the .05 level. 11 11

12. Illicit Drug Use

13. Drug Abuse Warning Network
Trends –

14. Trends in Nonmedical Use ED Visits – 2004 compared to 2008 -DAWN
ED visits due to opioid pain medications increased 112% between 2004 and 2008
Benzodiazepines increased 89%
Antipsychotics increased 56%
Most visits involved more than one drug
Source: SAMHSA / OAS 14

15. Trends for Opioid Non-medical Use ED Visits – 2004 - 2008
Source: DAWN Estimates, 2009 15

16. Number of Drugs per ED visit – 2008
Methadone (nonmedical use)
Hydrocodone (nonmedical use)
SAMHSA / OAS
Source: DAWN Estimates, 2009

17. Trends for Benzodiazepine Non-medical Use ED Visits, – 2004 - 2008
Source: DAWN Estimates, 2009 17

18. In Figure #3, from 1998 to 2007, alprazolam increased overall by 17
In Figure #3, from 1998 to 2007, alprazolam increased overall by 17.6 million prescriptions or 71%, from 24.8 million to 42.4 million prescriptions in 2007, and oxycodone increased by 26.4 million prescriptions or 166%, to 42.2 million prescriptions in 2007.
Oxycodone prescriptions increased by 166% from 1998 to 2007 and alprazolam increased by 71% in the same period.
Verispan, LLC: Vector One®: National, Years , Extracted 7/08

19. In Figure #18, 10 mg methadone was most commonly dispensed with a significant increase over the last 10 years. The ratio of females to males was approximately 1 to 1 with the majority of prescriptions dispensed to both genders aged years. Again, from Figure #2, the average increase in all methadone prescriptions rose from approximately 468 thousand in 1998 to 4.2 million in 2007, a nearly 800% increase.
10 mg strength is the most commonly dispensed with use gradually increasing over the past 10 years.
Ratio of dispensed methadone prescriptions for females to males is 1.1:1.
The majority of methadone prescriptions are dispensed to males and females aged years.
Verispan, LLC: Vector One®: National, Years , Extracted 7/08

20. The next three slides, Figures #21 through #23, will show some general statistics of total prescriptions dispensed sorted by gender from 2002 through 2007.
In Figure #21, which reflects opioids dispensed, for both females and males, hydrocodone is the most commonly dispensed drug followed by oxycodone. The use of propoxyphene has steadily declined in use over the last 10 years.
For both females and males hydrocodone is the most commonly dispensed agent followed by oxycodone.
Use of propoxyphene for the females and males has been gradually declining over the past 10 years.
Verispan, LLC: Vector One®: National, Years , Extracted 7/08

21. In Figure #22, which reflects benzodiazepines dispensed, alprazolam is the most commonly dispensed drug in females followed by lorazepam. In males, alprazolam is also the most commonly dispensed drug, however, clonazepam follows second. Overall, females fill more prescriptions for benzodiazepines compared to males.
51.8% increase of clonazepam, 49.1% increase of alprazolam, and 20.2% increase of lorazepam in males from 2002 to 2007.
45.6% increase of clonazepam, 29.8% increase of alprazolam, and 14.5% increase of lorazepam in females from 2002 to
For females alprazolam is the most commonly dispensed agent followed by lorazepam.
For males alprazolam is the most commonly dispensed agent followed by clonazepam.
Overall, more females fill a prescription for benzodiazepines compared to males.
Verispan, LLC: Vector One®: National, Years , Extracted 7/08

22. Prescription Drugs and Overdose Deaths

23. Three leading causes of injury death: United States, 1979--2007
Source: CDC/NCHS, National Vital Statistics System, Multiple Cause of Death 23

24. Poisoning deaths involving opioid analgesics, cocaine and heroin: United States, 1999–2007
The figure above shows the number of poisoning deaths involving opioid analgesics and other drugs or substances in the United States during 1999–2007. From 1999 to 2007, the number of U.S. poisoning deaths involving any opioid analgesic (e.g., oxycodone, methadone, or hydro-codone) more than tripled, from 4,041 to 14,459, or 36% of the 40,059 total poisoning deaths in In 1999, opioid analgesics were involved in 20% of the 19,741 poisoning deaths. During 1999–2007, the number of poisoning deaths involving specified drugs other than opioid analgesics increased from 9,262 to 12,790, and the number involving nonspecified drugs increased from 3,608 to 8,947.
NOTE: Drug categories are not mutually exclusive. Deaths involving more than one drug category shown in this figure are counted multiple times.
Source: CDC/NCHS, National Vital Statistics System, Multiple Cause of Death file 24 24

25. Drug Overdose Deaths in the U.S.
Drug overdose deaths in 2006 were second only to motor vehicle crash deaths among leading causes of unintentional injury death in the U.S.
Source: National Vital Statistics System as cited in CDC, Unintentional Drug Poisoning in the United States, Retrieved 3/19/10 from

26. Drug Overdose Deaths in the U.S.
States in the Appalachian region and the Southwest have the highest overall drug overdose death rates.

27. Two States
West Virginia
Utah

28. West Virginia
Used ME and Prescription Drug Monitoring Program to analyze all Rx drug abuse overdose deaths in 2006
Of 295 decedents, 198 (67.1%) were men and 271 (91.9%) were aged 18 through 54 years.
Pharmaceutical diversion was associated with 186 (63.1%) deaths while 63 (21.4%) were accompanied by evidence of doctor shopping.
Prevalence of diversion was greatest among decedents aged 18 through 24 years and decreased across each successive age group.
56% of decedents had no registered prescription for an opioid
20% had misrepresented themselves to 5 or more physicians to receive opioid prescriptions (“doctor shopping”).
Substance abuse indicators were identified in 279 decedents (94.6%), with nonmedical routes of exposure and illicit contributory drugs particularly prevalent among drug diverters. Multiple contributory substances were implicated in 234 deaths (79.3%).
Opioid analgesics were taken by 275 decedents (93.2%), of whom only 122 (44.4%) had ever been prescribed these drugs.
Around one third had a prescription for at the time of death.
Conclusion The majority of overdose deaths in West Virginia in 2006 were associated with nonmedical use and diversion of pharmaceuticals, primarily opioid analgesics

29. Drug Poisoning Deaths by Manner and Year — Utah 1991-2008
Unintentional fatalities due to prescription medications are an increasing problem in United States and in Utah. Starting in the year 2000, the Utah Medical Examiner noted an increase in the number of deaths occurring due to overdose of prescription opioid medications that are typically used for pain management.  Epidemiologic studies of data collected by the Office of the Medical Examiner, as well as from emergency department encounters and controlled substances dispensing confirmed the increases and uncovered an alarming problem. In this graph you can see the dramatic increase in unintentional or undetermined poisoning deaths (indicated by the blue line) that starts around the turn of the century. The following graphs will show more details about the blue line. As you can see, intentional deaths have remained relatively steady during the past two decades, therefore we have excluded suicides from our in-depth analysis and have looked at this problem as more of a patient safety problem. We believe that the problem in Utah is divided roughly into three areas: individuals who are dying from legitimately prescribed medications, individuals who are obtaining the medications illegally or fraudulently and are using them to get high and are dying, and then individuals who are a mix of the two. Our efforts have focused on reducing deaths due to unintentional or undetermined causes. 29

30. Number of Non-Illicit, Accidental and Intent Undetermined Deaths by Year & Drug
This slide shows the breakdown of deaths by year by opioid. Methadone was the most common drug identified by the Utah medical examiner as causing or contributing to accidental deaths, accounting for a disproportionate number of deaths compared to its frequency of use.  Methadone was the single drug most often associated with overdose death and had the highest prescription adjusted mortality rate (PAMR) with an average of 150 deaths for every 100,000 prescriptions during the study period (range: 89 deaths/100,000 prescriptions in 1998 to 224 deaths/100,000 prescriptions in 2004). From 1997–2004, population-adjusted methadone prescriptions increased 727%.  The rise in the methadone prescription rate was for treatment of pain and not addiction therapy. 
The numbers of prescriptions for four of the primary drugs of concern with respect to fatal drug overdose have increased at a greater rate than the growth of the Utah population.  The population-adjusted relative increase in prescribing for methadone and fentanyl exceeded 700% while oxycodone nearly tripled. 30

31. Distribution of Decedents by Numbers of Drugs as COD (N=214)
Number of drugs as COD
Decedents
n (%) 1
56 (26) 2
43 (20) 3
63 (29) 4
36 (17) 5
12 (6)
6 or more
4 (2) 31

32. Prescription Pain Medication Misuse/Abuse (N=198)
61% had signs of misuse/abuse
Defined as:
At least one of the following indicators:
Obtained medications from non-provider
Took more than prescribed daily
Used for non-pain reasons
≥5 doctors prescribed in last year
61% of decedents were reported to show signs of prescription pain medication misuse and/or abuse. The remaining 39% did not have signs of misuse or abuse.
A decedent was said to show signs of prescription pain medication misuse and/or abuse if they had at least one of the following indicators: they obtained prescription pain medications from a source other than a provider, took more than prescribed on a daily basis, used prescription pain medication for reasons other than to treat pain, or filled a prescription for opioids in the year prior to their death from 5 or more providers. Interview data was used for the first three indicators, and Controlled Substance Database data was used for the fourth. 32 32

33. Chronic Pain, Mental Illness, and Obesity (N=214)
Characteristic
Decedents
n (%)
Suffered from chronic pain
176 (82)
Diagnosed with mental illness
105 (49)
Obese (BMI ≥30)
79 (37)
This table shows characteristics of the decedent population regarding chronic pain, mental illness, and obesity. Obesity was defined as having a body mass index, or BMI, of 30 or greater, which was calculated using data collected by the medical examiner at the time of death.
Interviewees reported that 82% of decedents suffered from chronic pain. For context on chronic vs. acute pain, in a recent survey, the majority of Utah adults who were prescribed opioids reported being prescribed for acute pain. Continuing with the results in the table, having been diagnosed with a mental illness was reported for 49% of decedents, and 37% were obese. 33 33

34. Legislation in 2007: HB 137 Three Mandates
Research
Causes, risk factors, solutions
Prescribing Guidelines
“medical treatment and quality care guidelines that are scientifically based; and peer reviewed”
Educate
Health care providers, Patients, Insurers, Public
Brad Daw enlisted by DOH

35. 2008 data Reduction in number of deaths (largest in 18 years)
Numbers are back up in 2009 35

36. 51 opioid-related overdoses were identified, including 6 deaths.
How can PDMPs Reduce Opioid Overdose Risk? – Dunn, et al, 2010, Annals of Internal Med
51 opioid-related overdoses were identified, including 6 deaths.
Compared with patients receiving 1 to 20 mg/d of opioids (0.2% annual overdose rate),
patients receiving 50 to 99 mg/d had a 3.7-fold increase in overdose risk (95% CI, 1.5 to 9.5) and a 0.7% annual overdose rate.
Patients receiving 100 mg/d or more had an 8.9-fold increase in overdose risk (CI, 4.0 to 19.7) and a 1.8% annual overdose rate.

37. Physician Education Opioid Prescribing 4-8 Hour CME
Problems we see with patients who are prescribed opioids for persistent pain
Deciding whether or not to prescribe an opioid
Pharmacology, emphasis on methadone
Steps to take if you decide to use opioids in the treatment of persistent pain
Steps to take if you decide NOT to use opioids in the treatment of persistent pain:
The practical side of patient monitoring – PMP, screening, lost Rx, etc.
When, why and how to stop prescribing opioids and manage the patient with another treatment approach

38. Pain or Addiction? The Four “A’s” of Pain Treatment Outcomes
Analgesia (pain relief)
Activities of daily living (psychosocial functioning)
Adverse effects (side effects)
Aberrant drug taking (addiction- related outcomes)
This slide is from an “expert” (Passik) on the pain/addiction interface. What every physician who prescribes an narcotic analgesic should be aware of.
Passik & Weinreb, 1998

39. Aberrant Drug- Taking Behaviors: The Model
Probably more predictive
-Selling prescription drugs
-Prescription forgery
-Stealing or borrowing another patient’s drugs
-Injecting oral formulation
-Obtaining prescription drugs from non-medical sources
-Concurrent abuse of related illicit drugs
-Multiple unsanctioned dose escalations
-Recurrent prescriptions losses
Helps practitioners to judge whether or not patients are crossing the line from pain treatment to addiction.
Passik and Portenoy, 1998

40. Aberrant Drug- Taking Behaviors: The Model (continued)
Probably less predictive
-Aggressive complaining about need for higher doses
-Drug hoarding during periods of reduced symptoms
-Requesting specific drugs
-Acquisition of similar drugs from other medical sources
-Unsanctioned dose escalation 1-2 times
-Unapproved use of the drug to treat another symptom
-Reporting psychic effects not intended by the clinician
Passik and Portenoy, 1998

41. The point on this slide is that you can examine a sample of prescription pain patients. More than half don’t demonstrate any aberrant behavior at all. But, around 6 percent demonstrate several. It is that 6% or so that we need to do something about.

42. Summary Drug Abuse and Rx drug abuse increasing
Data reflect poly drug exposure
Availability has been increasing commensurably
Prescription drug overdoses have increased with increasing abuse
PMPs, dosing guidelines, prescriber/consumer educations programs in place to address prescription drug overdose problems
Effective?