Bringing the full power of science to bear on drug abuse and addiction Nora D Volkow MD Director National Institute on Drug Abuse Advancing Addiction Science to Address the Opioid Crisis ID: 804955
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National Institute on Drug AbuseBringing the full power of science to bear on drug abuse and addictionNora D. Volkow, M.D.DirectorNational Institute on Drug Abuse
Advancing Addiction Science to Address the Opioid Crisis
Advancing Addiction Science
Wilson M. Compton, M.D., M.P.E.
Deputy Director
National Institute on Drug Abuse
Science = Solutions
Slide2And preliminary estimates suggest a 20% further increase in OD deaths in 2016….
Source: DC NCHS 2017.
U.S. Overdose Crisis:
52,404 Deaths
in 2015 (33,091 from Prescription and Illicit Opioids)
Slide3Marked Geographic and Temporal Variation in Overdose Deaths : Estimated Age-adjusted Death Rates for Drug Poisoning by County
2015
1999
https://www.cdc.gov/nchs/data-visualization/drug-poisoning-mortality/
Slide4Other Synthetic Opioids
(e.g. fentanyl)
Commonly Prescribed Opioids
(natural and semi-synthetic opioids and methadone)
Heroin
Any Opioid
Overdose Deaths Primarily from Opioids: Prescription Drugs, Heroin and Synthetics (i.e. Fentanyl and similar)
Slide5ENVIRONMENTAL AVAILABILITY: Current Opioid Crisis Originated with Prescribing Increases Opioid prescriptions Tripled to MORE THAN 200 MILLION prescriptions in recent years
Slide6People Misusing Analgesics Obtain them Directly & Indirectly by Prescription
Source where pain relievers obtained for most recent misuse
Friend/
Relative
Prescription
Other
Their Prescription
Their Friend/Relative
Other
Source: Han, Compton, et al. Annals of Internal Medicine 2017;167(5):293-301
Source where pain relievers obtained for most recent misuse
Friend/
Relative
Prescription
Other
Their Prescription
Their Friend/Relative
Other
Source: Han, Compton, et al. Annals of Internal Medicine 2017;167(5):293-301
Slide7Most Heroin Users Report Previous Non-Medical Use of Prescription Opioids,National General Population: Within 5 years, 3.6% of non-medical users of opioids progressed to heroin within 5 years (i.e. less than 1% per year)
(Muhuri, Gfroerer, Davies. 2013)
Local Longitudinal Study of Non-medical users:
Within 3 years, 7.5% progressed to heroin (i.e. 2.8% per year) (Carlson, Nahhas, martins, Daniulaityte. 2015)
BUT Only a
Small Proportion of Non-Medical Users Progress to Heroin
Slide8Rx Opioid Misuse has been a Risk Factor for Heroin Use% Heroin Treatment Admissions that Used Heroin or Rx Opioid First
Source: Cicero et al. JAMA Psychiatry. 2014;71(7):821-826.
Most current heroin users started opioid use with prescription opioids
.
Decade of First Opioid Use (No. of Abusers)
Slide9Heroin Users: First Opioid Now Likely to be HeroinSource: Cicero T et al.
Addictive Behaviors 2017;74:63-66
Slide10ECONOMICS: Heroin Increases Due to Lower Price and Greater AvailabilityNational Drug Control Strategy--Data Supplement 2014. https://www.whitehouse.gov/sites/default/files/ondcp/policy-and-research/ndcs_data_supplement_2014.pdf
Slide11Fentanyl and Counterfeit Products Broaden At-Risk Population
Source: Jones CM, et al. AJPH 2017,
Mar;107(3):430-432.
Slide12Graphs from NY Times Article based on CDC MMWR Report 2017
2016 Fentanyl-Related Deaths Surpassed Heroin or Rx
Slide13ECONOMICS: CHEAP Fentanyl Precursor Chemicals
Slide14Fentanyl and Fentanyl Analogs Impacting Multiple States
Source: MMWR Oct 27, 2017 (early release)
Slide15Increasing Prenatal Exposure
Admissions for Newborn Withdrawal Syndromes (Number per 1000 Admissions)
Source: Tolia VN, Patrick SW, et al. NEJM 2015;372:2118-2126
Science
= Solutions
Slide16Counties Deemed Highly Vulnerable to Rapid Dissemination of HCV or HIVSource: Van Handel et al, JAIDS 2016
Rising rates of HCV
Suryaprasad et al. Clin Infect Dis. 2014
HIV
(and
Hepatitis C
) Outbreak Linked to Oxymorphone Injection Use in Indiana, 2015
Peters et al.
The
New England Journal of Medicine 2016;375:229-239
Slide17Science = Solutions: Using Research to Improve HIV and Hepatitis C in Rural AreasNIH is partnering with the CDC, SAMHSA and the Appalachian Regional Commission (ARC) to conduct research to address increased opioid injection drug use and resulting overdose, HIV and Hepatitis C infection.
Improve understanding problem’s scope; contributing health trends
Identify resources, obstacles
Develop intervention approaches to address these health threats
Slide18PercentOpioid AnalgesicsBenzodiazepines
Source: CM Jones, JK McAninch.
American Journal of Preventive Medicine 2015;49:493-501.
AAPC = 8.4% (95% CI 7.1%-9.7%)
AAPC = 1.5% (95% CI 0.8%-2.2%)
Overlap of
Benzodiazepines and Opioids
Opioid Analgesic ED Visits and OD Deaths Involving Benzodiazepines & Benzodiazepine ED Visits and OD Deaths Involving Opioids
Science =
Solutions
Slide19U.S. Department of Health and Human Services OPIOID STRATEGY
Improving access to prevention, treatment, and recovery services
Targeting availability and distribution of overdose-reversing drugs
Strengthening timely public health data and reporting
Supporting cutting-edge research
Advancing the practice of pain management
Comprehensive
Evidence-based
Targets drivers of epidemic
Flexible to emerging threats
Slide20Doctors Continue to Prescribe Opioids for Ninety-one Percent of Overdose PatientsSource: Larochelle et al.
Ann Intern Med. 2016;164(1):1-9.
10%
14%
13%
63%
of high-dose opioid pts
still on high dose 31-90 days after
OD
17% of high- dose patients overdosed again within two years
In a
2-year follow-up of 2848 commercially insured patients who had a nonfatal opioid overdose
during long-term opioid therapy :
33-39% of those with active opioid prescriptions during follow-up also were prescribed benzodiazepines.
Slide21Inadequate Pain Treatment as a Driver?
1.9 million adults had
prescription opioid use disorders (0.8% of the U.S. adult population)
91.8 million adults
used prescription opioids
(37.8% of the U.S. adult population)
11.5 million adults
misused prescription opioids
(4.7% of the U.S. adult population)
Source:
Han, Compton, et al. Annals of Internal Medicine 2017 (epub Aug 1, 2017)
Slide22Limited Medical Education on Pain (and Addiction) Mezei L, et al. Pain education in North American medical schools
J Pain. 2011
Number of med schools teaching 0 to 5 hours, 5 to 10 hours, etc..
U.S. medical schools dark gray bars, Canadian schools light gray.
Pain Education in USA:
9 Mean Hours
(range 1-31)
Slide23Opioid Prescribing
Guidelines
Intended for primary care providers
Applies to patients >18 years old in chronic pain outside of end-of-life care
Builds on joint CDC, NIDA, ONC, SAMHSA summary on “Common Elements in Guidelines for Prescribing Opioids for Chronic Pain” and the NIH Pathways to Prevention for Opioids in Treating Chronic Pain
PUBLISHED MARCH 15, 2016
Recent Landscape for Guidelines:
Small Number
Outdated
Not Conflict Free
Solution….
Slide24Resources for Medical Students, Resident Physicians & Faculty
Web training on pain assessment and treatment
Archived NIDA CME Courses:
Safe Prescribing for Pain
Managing Pain Patients
Who Abuse Rx Drugs
Opioid Education
Upcoming NIDA CME Course:
Adolescent Substance Use (Prescription Opioid Module)
Bringing NIDA research to clinical practice
Medical schools have developed innovative curriculum resources about how to identify and treat patients with substance use disorders
Slide25Opioid Morphine Milligram Equivalents Prescribed Declined 23.1% from 3rd quarter 2010 to 2nd quarter 2016
Recent Declines in Opioid Prescriptions
Slide26RESEARCH TARGET: Safe, Effective Strategies for Pain Management
Slide27Soergel DG, et al., Pain 2014. Manglik A, et al.,
Nature 2016. DeWire SM, et al., JPET
2013. Bohn LM, et al., Science 1999
A Promising New Generation Of Pain
Therapeutics
Science
=
Solutions
Biased Mu-Opioid Receptor Ligands
Slide28Direct Overdose InterventionNaloxone Distribution for opioid overdose victims. The potential for direct intervention to save lives.
“Evzio” naloxone auto-injector APPROVED BY FDA, April 3, 2014
Science
=
Solutions
“Narcan Nasal Spray” naloxone APPROVED BY FDA, November 18, 2015
Slide29Receptor occupancy by INTRANASAL equivalent to INTRAVENOUS Naloxone
Baseline
Phillip et al. J Pharmacol Exp Ther 2016
Intranasal
Intravenous
NALOXONE REQUIRES FAST AND EFFICIENT DELIVERY as achieved with iv injection
but few know how to inject
Intranasal Narcan
Injectable
Blood Concentration
Positive pharmacology of nasal naloxone:
Rapid onset and high peak blood level
Slide30Retail Pharmacy Prescriptions for Naloxone Increase MarkedlyRetail prescriptions show an increase of 9520% from the 4
th quarter of 2013 to 2nd quarter 2016.
Outpatient prescribing of naloxone may complement community-based distribution and first responder access.
Sources: Jones CM, Lurie PG, Compton WM. Am J Public Health. 2016;106(4):689-690; IMS Health, published https://www.performance.gov/content/reduce-opioid-related-morbidity-and-mortality
Science
=
Solutions
2014
2015
2016
Slide31New stronger, longer acting formulations to address more potent opioids (e.g. fentanyl)
Stimulation devices to prevent respiratory depression
Overdose detection and alert
technologies
Post-overdose interventions to ensure engagement in treatment
An early prototype of a device students at the University of
British Columbia have created to detect drug overdoses. (THE CANADIAN PRESS/HO-Courtesy of Sampath Satti )
Capnography.com
CO2 Sampling/O2 delivery for
non-intubated patients.
Source: Oridion Capnography, Inc.
Overdose Treatment Research:
Saving Lives for Future Recovery
Slide32ADDICTIONS as Diseases of Gene-Environment-Development
Environment
Addiction
DRUG/ALCOHOL
Brain Mechanisms
Biology
Genes/Development
Age
Slide33The Environment Matters: Universal Family-Based Drug Abuse Prevention Reduces Prescription Drug Misuse
In this study, for 100 young adults in general population starting Rx abuse, only 35 from an intervention community started.
**p<.01; ***p<.001; Relative Reduction Rates (RRRs)= 65-93%
Notes: General=Misuse of narcotics or CNS depressants or stimulants.
Source: R Spoth et al.
American Journal of Public Health
2013
Three studies now suggest the impact of universal prevention on prescription drug abuse.
Science
=
Solutions
Slide34Brody GH, et al. Protective Prevention Effects on the Association of Poverty With Brain Development. JAMA Pediatr. Published online November 28, 2016. doi:10.1001/jamapediatrics.2016.2988
Figure: Effect of Family Poverty on Youth Brain Region by Intervention Status
. GCL=dentate gyrus. SAAF=Strong African American Families intervention.
The Environment Matters
Previous work showed that high supportive parenting decreased substance use risk.
Recent study now shows that
brain development can be normalized
.
Science
= Solutions
More years in poverty as a teen = smaller brain volumes.
More years in poverty as a teen = smaller brain volumes.
With the SAAF intervention, no difference in brain volume.
With the SAAF intervention, no difference in brain volume.
Slide35Medications are Effective for Opioid Use DisorderMedication Assisted Treatment (MAT) DECREASES:
Opioid useOpioid-related overdose deaths
Criminal activityInfectious disease transmission
And INCREASES
Social functioning
Retention in treatment
Kakko J et al., The Lancet 2003.
Slide36Medications are Underused
In 2014, only 25% of opioid admissions had treatment plans that included receiving medications.
Treatment Episode Data Set (TEDS): 2004-2014.
Jones C et al., Am J Public Health 2015.
In 48 states and D.C., Opioid Abuse and Dependence Rates Exceed Buprenorphine Treatment Capacity
Slide37Probuphine: buprenorphine implant; releases sustained dose for up to 6 months (FDA Approval May 26, 2016)Initiating buprenorphine treatment in the emergency department improves treatment engagement and reduces illicit opioid use
Extended release naltrexone initiated in criminal justice
settings lowers relapse rates and overdosesAbstinence from opioids over 12 Weeks with interim buprenorphine
Science Driven Solutions:
Improving Addiction Treatment
Lee JD, et al., Addiction 2015;100:1005-1014
and New Eng J Med 2016;374:1232-1242
Abstinence with
Interim Buprenorphine
Sigmon SC et al. N Engl J Med 2016.
Slide38Science = Solutions: Using Research to Improve Access to MAT in the Context of SAMHSA Access to Recovery GrantsCALIFORNIA: PATIENT DECISION AID FOR MEDICATION-ASSISTED TREATMENT FOR OPIOID USE DISORDER (PI: Yih-Ing Hser, UCLA)
ILLINOIS: RECOVERY INITIATION AND MANAGEMENT AFTER OVERDOSE (RIMO) EXPERIMENT (PI: Christy Scott, Chestnut Health Systems)
INDIANA: PROJECT POINT--EFFECTIVENESS AND SCALABILITY OF AN OVERDOSE SURVIVOR INTERVENTION (PI: Dennis Paul Watson, Purdue/Indiana University)RHODE ISLAND: COMPARING MEDICATION MAINTENANCE IN COMPREHENSIVE COMMUNITY AND PHARMACY SETTINGS TO ENHANCE ENGAGEMENT (PI: Traci Green, Rhode Island Hospital)
WASHINGTON: HUB AND SPOKE MODEL TO IMPROVE PHARMACOTHERAPY USE FOR OPIOID ADDICTION AND PROMOTE RECOVERY (PI: Sharon Reif, Brandeis)
Slide39Non-Pharmacological Treatments for Addiction
Salling and Martinez, 2016.
Transcranial Direct
Current Simulation (tDCS)
Deep Brain Stimulation (DBS)
Implanted electrodes emit electrical
stimulation to targeted brain region
Transcranial Magnetic
Stimulation (TMS)
Slide40Inadequate linkage to care following overdose resuscitation.Inadequate duration of care.
Other Issues….
OUD Cascade of Care in USA
Current estimates
Treatment gap
90% goal
Williams AR, Nunes E, Olfson M. Health Affairs Blog, 2017
Slide41Using Research to End the Opioid CrisisNIH Opioid Research Initiative
PAIN MANAGEMENT
Safe, effective, non-addictive strategies
OPIOID ADDICTION
TREATMENT
New, innovative medications and technologies
OVERDOSE REVERSAL
Interventions to reduce mortality and link to treatment
Non-Opioid
Analgesics
Biomarkers
For Pain
Opioid Vaccines
Nonpharmacological
Treatments (e.g. TMS)
Respiratory Stimulation Devices
Slide42Released November 1, 2017
Slide43Complex biological, developmental and social aspects of substance use and addiction suggest multipronged responses.Summary:
Advancing Addiction Science
www.drugabuse.gov
Science
=
Solutions