Comprehensive Approaches to Understanding and
Addressing the Heroin Epidemic
Kelly Dunn, Ph.D.
Assistant Professor; Johns Hopkins School of Medicine
Department of Psychiatry and Behavioral Sciences
1
Talk Outline
• Why is opioid use disorder so prevalent?
• Are there ways to improve treatment for
opioids?
• How do we address opioid overdose?
• Areas for future research
2
Talk Outline
• Why is opioid use disorder so prevalent?
• Are there ways to improve treatment for
opioids?
• How do we address opioid overdose?
• Areas for future research
3
Treatment of Pain is a Billion Dollar Industry
IMS Health, National Prescription Audit, Dec 2013
4
Narcotics are Among the Top 5 Prescribed
Medications
IMS Health, National Prescription Audit, Dec 2013
5
Top Generic Prescriptions (2010)
1. Hydrocodone + acetaminophen [Vicodin] (n=122,806,850)
18. Oxycodone + acetaminophen [Percocet] (n=28,705,243)
46. Propoxyphene + acetaminophen [Darvon] (n=14,274,354)
51. Oxycodone (n=12,652,375)
114. Fentanyl patch (n=4,914,785)
121. Methadone (n=4,558,532)
170. Morphine (n=2,740,358)
192. Hydromorphone [Dilaudid] (n=2,272,481)
•
Top 200 generic drugs by units in 2010. SDI’s Vector One® National
Opioid Prescriptions Dispensed
Drug Availability Corresponds to Drug Use
• Past Year Initiates to Substance Abuse (2012)
NSDUH, 2013
8
PO Abuse
• In 2012, oxycodone
and hydrocodone
were the 2 most
popular opioid
medications abused
(preferred by 75%
of 3520 drug
treatment
admissions)
Hydrocodone
Oxycodone
– Hydrocodone
preferred for pain
– Oxycodone
preferred for high
Cicero et al., 2013, Pain Vol. 154
9
So If PO’s Are So Widely Available, Why is
Heroin Use Increasing?
10
Abuse Deterrent Formulations
US Department of Justice, Drug Enforcement Agency National Drug Threat Assessment Summary (2013)
11
Why is Heroin Use Increasing?
12
Route of Administration
• Change in OxyContin formulation means that pill was being used orally
instead of IV/IN
– May require much larger quantities of oral OxyContin to meet demands for
physiological tolerance in IV drug users
– There are very few (if any?) prescription opioid substitutes for OxyContin IV use
because most others are compounded with NSAIDs (acetaminophen, aspirin)
13
Decline in OxyContin Use Corresponds to
INCREASE in Heroin Use
Cicero et al., 2012, NEJM Vol. 367 (2)
14
Talk Outline
• Why is opioid use disorder so prevalent?
• Are there ways to improve treatment for opioids?
– Improved detoxification paradigms
– Reduce the abuse liability of prescription opioids (slow
the formation of dependence)
– Develop extended release formulations of agonist
replacement therapies
• How do we address opioid overdose?
• Areas for future research
15
Opioid Users Require Extensive Treatment
Experience Before Abstaining
• Opioid users enter treatment an average of 8 times before staying
abstinent.
Hser (2007). Eval Rev, Vol. 31
Opioid Users Require Extensive Treatment
Experience Before Abstaining
Hser et al., (2008). Addictive Behaviors, Vol. 33
Improved Detoxification Paradigms
• Evaluated 1, 2, or 4 week buprenorphine taper for the
treatment of PO dependence
Sigmon, Dunn et al., (2013). JAMA Psychiatry, Vol. 70 (12)
Improved Detoxification Paradigms
• 4-week taper produced greater reductions in opioid-positive UA’s and
higher likelihood of beginning naltrexone treatment
Sigmon, Dunn et al., (2013). JAMA Psychiatry, Vol. 70 (12)
Reduce the abuse liability of prescription opioids
(slow the formation of dependence)
•
Aversive Reactants
–
–
–
–
•
–
–
–
Opana (oxymorphone)
OxyContin (Reformulated)
Small Molecule Delivery
–
•
Methadone (pill): Burns
Oxecta (oxycodone + Niacin): Burns
Embeda (morphine + naltrexone)
Oxytrex (oxycodone + naltrexone)
Sustained Release Formulations:
Non-Crushable:
–
–
•
•
NKTR-181: Enters system at a rate 90%
slower than traditional opioids (thus has
lower abuse potential)
DETERx
–
Technology w/small beads of medicine in a
capsule that is tamper-resistant, maintains
extended release properties, and has high
melting point (e.g., no IV)
•
Depot injections: Vivitrol (naltrexone)
Probuphine (implantable rods that release
buprenorphine over 6 months)
Exalgo (OROS hydromorphone): osmotic
shell with semipermeable tablet
membrane that slowly releases
hydromorphone and makes it difficult to
extract the drug
Bioactivated Drugs
–
–
Bio-MD: Drug must contact amino acid in
small intestine/stomach to become
activated (therefore must be ingested)
Multi-Pill Abuse Resistance (MPAR)
(Hydromorphone, oxymorphone,
morphine, oxycodone, hydrocodone):
Combining 10 pills yields same result as 2
pills (reduced overdose risk)
Abuse Deterrent Formulations are Important to Reduce
Prevalence of Opioid Use
Abuse Deterrent Formulations
• Researched Abuse, Diversion, and AddictionRelated Surveillance System (RADARs)
– Evaluated effect of reformulated OxyContin and Opana
RADARs Newsletter, 2013. Vol. 8(3), (Richard Dart)
22
Abuse Deterrent Formulations
RADARs Newsletter; 2013. Vol 8(3), (Richard Dart)
23
Abuse Deterrent Formulations
24
Abuse Deterrent Formulations
Rosenthal et al., 2013. Addiction, Vol. 108
25
Talk Outline
• Why is opioid use disorder so prevalent?
• Are there ways to improve treatment for
opioids?
• How do we address opioid overdose?
• Areas for future research
26
Opioid-related Overdose is Increasing
• Opioid OD has increased • Significantly more likely
in all segments of
to occur following
society:
change in tolerance
–
–
–
–
–
–
–
Drug users
Chronic pain patients
Elderly
Children
Women
Adolescents
Homeless Individuals
– Detoxification
– Leaving jail or prison
– Induction onto methadone
treatment
Baggett et al., 2013; Bailey et al., 2009; Bohnert et al., 2011; Cobaugh et al., 2006; Coben et al., 2010; Dunn et al., 2010; Palmiere et
al., 2010; Paulozzi et al., 2006; Rosca et al., 2012
Abuse Deterrent Formulations
CDC, National Center for Health Statistics, National Vital Statistics System
28
Opioid OD Rates Increase as a Function of Drug
Availability
OPR Sales
(2008)
Rates of PO related deaths, treatment
admissions, and kilograms of PO’s
sold
OPR
Deaths
(2008)
29
MMWR, 2011. Vol. 60 (43)
Overdose Reversal
• Naloxone (Narcan) is an
antidote to opioid OD
• Reverses opioid-ODs
– No other side effects
• Available in IV/IM and IN
formulations
– All formulations reverse OD ~8
min following administration
– IN version is not yet FDAapproved
There are Substantial and Impressive Nationwide Efforts to Train
and Distribute Naloxone to Bystanders for OD Intervention
31
MMWR, 2012. Vol 61 (6)
Overdose Reversal
• Legal barriers make prescription of naloxone to users difficult
– Physicians often cannot prescribe for 3rd party use
– Good Samaritan Laws are needed to support bystander intervention
• Civil immunity for person calling 911 and for the person overdosing
• Civil/Criminal immunity for administration of naloxone
– (Unsupported) fear that OD antidote will promote more ODs
http://www.anypositivechange.org/menu.html
The Maryland Government is Supporting Naloxone
34
http://adaa.dhmh.maryland.gov/NALOXONE/SitePages/Home.aspx
New Naloxone Products in Pipeline
Brief Assessment of Opioid Knowledge
Talk Outline
• Why is opioid use disorder so prevalent?
• Are there ways to improve treatment for
opioids?
• How can we further prevent opioid-related
problems?
• Areas for future research
37
Areas for Future Research
• How can we treat pain among opioid-dependent patients?
– No strong empirical data or clinical guidelines
• Are there methods to reduce our societal reliance on opioid
analgesics for pain?
– Combining opioids with cannabinoids may enhance analgesic effect
of opioids- thus requiring lower doses of opioids
• Understand the pharmacogenomic contribution to opioid
dependence
– Several genes have been associated with differential responses to
opioids
38
Conclusion
• Increased opioid use corresponds to increased number of
analgesic prescriptions
• Introduction of abuse deterrent formulations will reduce
reliance on PO’s, but may prompt increase in heroin use
• New treatment strategies include tapering programs are
needed
• Increased availability and use of opioids has increased
opioid OD rates, and more prevention efforts are needed
• Ways to reduce opioid use, including treatment of comorbid
pain/opioid dependence and methods to enhance opioid
analgesic effects are needed
39
Thank you!
Contact me at:
Kelly Dunn, Ph.D.
kdunn9@jhmi.edu
P: 410-550-2254
40