Advancing Addiction Science to Address the Opioid Crisis

Transcription

1 Advancing Addiction Science to Address the Opioid Crisis National Institute on Drug Abuse Bringing the full power of science to bear on drug abuse and addiction Nora D. Volkow, M.D. Director National Institute on Drug Abuse Science = Solutions Advancing Addiction Science Wilson M. Compton, M.D., M.P.E. Deputy Director National Institute on Drug Abuse

2 Overdose Deaths Increased Markedly in ,000 60,000 63,632 50,000 40,000 47,055 52,404 30,000 20,000 10, ,

3 Virtually All of the U.S. Have Increased Drug Overdoses: Estimated Age-adjusted Death Rates for Drug Poisoning by County

4 Overdose Deaths Primarily from Opioids: Prescription Drugs, Heroin and Synthetics (i.e. Fentanyl and similar) Other Synthetic Opioids (e.g. fentanyl) Commonly Prescribed Opioids (natural and semi-synthetic opioids and methadone) Heroin Methadone

5 ENVIRONMENTAL AVAILABILITY: Current Opioid Crisis Originated with Prescribing Increases 250 Opioid prescriptions Tripled to MORE THAN 200 MILLION prescriptions in recent years Opioid Prescriptions in MILLIONS

6 People Misusing Analgesics Obtain them Directly & Indirectly by Prescription Source where pain relievers obtained for most recent misuse Prescription 36% Friend/ Relative 87% Their Prescription 10% Other 54% Other 3% 10% Their Friend/Relative Source: Han, Compton, et al. Annals of Internal Medicine 2017;167(5):

7 Women suffer more pain in many categories and are prescribed more opioids Rates of U.S. Adults > 18 and Older Reporting Pain, Severe headache or migraine Number of `Prescription Low back pain Males Females Men Neck pain Women CDC and NCHS, 2015 Opioid Prescriptions U.S. Retail Pharmacies, Source: IMS Health, National Prescription Audit

8 Analgesic Mechanisms of Mu Opiate Drugs (Heroin, Vicodin, Morphine) ACC (pain) Accumbens (reward) PAG (pain) Thalamus (pain)

9 Rx Opioid Misuse has been a Risk Factor for Heroin Use % Heroin Treatment Admissions that Used Heroin or Rx Opioid First Most current heroin users started opioid use with prescription opioids. Decade of First Opioid Use (No. of Abusers) Source: Cicero et al. JAMA Psychiatry. 2014;71(7):

10 Most Heroin Users Report Previous Non-Medical Use of Prescription Opioids, BUT Only a Small Proportion of Non-Medical Users Progress to Heroin 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)

11 Heroin Users: First Opioid Now Likely to be Heroin Source: Cicero T et al. Addictive Behaviors 2017;74:63-66

12 ECONOMICS: Heroin Increases Due to Lower Price and Greater Availability $3,500 "Retail" Price Per Pure Gram $3,000 $2,500 $2,000 $1,500 $1,000 $500 $ National Drug Control Strategy--Data Supplement

13 Fentanyl and Counterfeit Products Broaden Risk Population Source: Jones CM, et al. AJPH 2017, Mar;107(3):

14 2016 Fentanyl-Related Deaths Surpassed Heroin or Rx Graphs from NY Times Article based on CDC MMWR Report 2017

15 ECONOMICS: CHEAP Fentanyl Precursor Chemicals

16 Increasing Prenatal Exposure Admissions for Newborn Withdrawal Syndromes (Number per 1000 Admissions) Source: Tolia VN, Patrick SW, et al. NEJM 2015;372: Science = Solutions

17 Rising rates of HCV Counties Deemed Highly Vulnerable to Rapid Dissemination of HCV or HIV Suryaprasad et al. Clin Infect Dis HIV (and Hepatitis C) Outbreak Linked to Oxymorphone Injection Use in Indiana, 2015 Peters et al. The New England Journal of Medicine 2016;375: Source: Van Handel et al, JAIDS 2016

18 Science = Solutions: Using Research to Improve HIV and Hepatitis C in Rural Areas NIH 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

19 Overlap of Benzodiazepines and Opioids Opioid Analgesic ED Visits and OD Deaths Involving Benzodiazepines & Benzodiazepine ED Visits and OD Deaths Involving Opioids AAPC = 1.5% (95% CI 0.8%-2.2%) Percent AAPC = 8.4% (95% CI 7.1%-9.7%) 0 Opioid Analgesic Deaths Involving Benzodiazepines Opioid Analgesics Benzodiazepine Deaths Involving Opioid Analgesics Benzodiazepines Source: CM Jones, JK McAninch. American Journal of Preventive Medicine 2015;49: Science = Solutions

20 U.S. Department of Health and Human Services OPIOID STRATEGY Targeting availability and distribution of overdosereversing drugs Advancing the practice of pain management Comprehensive Evidence-based Targets drivers of epidemic Flexible to emerging threats Improving access to prevention, treatment, and recovery services Supporting cutting-edge research Strengthening timely public health data and reporting

21 Inadequate Pain Treatment as a Driver? 91.8 million adults used prescription opioids (37.8% of the U.S. adult population) million adults misused prescription opioids (4.7% of the U.S. adult population) 1.9 million adults had prescription opioid use disorders (0.8% of the U.S. adult population) relieve physical pain 4.6 relax or relieve tension experiment get high or feel good help with sleep help with emotions or feelings increase/decrease effects of other drugs hooked or have to misuse other reason 8.9 Source: Han, Compton, et al. Annals of Internal Medicine 2017 (epub Aug 1, 2017)

22 Limited Medical Education on Pain (and Addiction) Pain Education in USA: 9 Mean Hours (range 1-31) 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. Mezei L, et al. Pain education in North American medical schools J Pain. 2011

23 Doctors Continue to Prescribe Opioids for Ninety-one Percent of Overdose Patients In a 2-year follow-up of 2848 commercially insured patients who had a nonfatal opioid overdose during long-term opioid therapy : 14% 13% 63% of highdose opioid pts still on high dose days after OD 17% of high- dose patients overdosed again within two years high dose moderate dose low dose none Ø33-39% of those with active opioid prescriptions during follow-up also were prescribed benzodiazepines. Source: Larochelle et al. Ann Intern Med. 2016;164(1):1-9.

24 Ø Recent Landscape for Guidelines: Small Number Outdated Not Conflict Free ØSolution. Opioid Prescribing Guidelines Ø Intended for primary care providers Ø Applies to patients >18 years old in chronic pain outside of end-of-life care Ø 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 Ø PUBLISHED MARCH 15, 2016

25 Opioid Education Resources for Medical Students, Resident Physicians & Faculty Medical schools have developed innovative curriculum resources about how to identify and treat patients with substance use disorders Web training on pain assessment and treatment Archived NIDA CME Courses: Safe Prescribing for Pain Managing Pain Patients Who Abuse Rx Drugs Bringing NIDA research to clinical practice Upcoming NIDA CME Course: Adolescent Substance Use (Prescription Opioid Module)

26 Recent Declines in Opioid Prescriptions 70 Opioid MME in BILLIONS Opioid Morphine Milligram Equivalents Prescribed Declined 23.1% from 3 rd quarter 2010 to 2 nd quarter Q2010 2Q2010 3Q2010 4Q2010 1Q2011 2Q2011 3Q2011 4Q2011 1Q2012 2Q2012 3Q2012 4Q2012 1Q2013 2Q2013 3Q2013 4Q2013 1Q2014 2Q2014 3Q2014 4Q2014 1Q2015 2Q2015 3Q2015 4Q2015 1Q2016 2Q2016

27 RESEARCH TARGET: Safe, Effective Strategies for Pain Management

28 A Promising New Generation Of Pain Therapeutics Biased Mu-Opioid Receptor Ligands Soergel DG, et al., Pain Manglik A, et al., Nature DeWire SM, et al., JPET Bohn LM, et al., Science 1999 Science = Solutions

29 Research on the Neurobiology of Pain Gender Differences in Kappa Opioid Receptor Availability Males Female s Males had higher K opioid receptor availability than females presumably from increased dynorphin. Could this help explain gender differences in pain catastrophizing?? Vijay et al., Am J Nucl Med Mol Imaging (4):

30 Direct Overdose Intervention Naloxone Distribution for opioid overdose victims. The potential for direct intervention to save lives. Ø Evzio naloxone auto-injector APPROVED BY FDA, April 3, 2014 Ø Narcan Nasal Spray naloxone APPROVED BY FDA, November 18, 2015 Science = Solutions

31 NALOXONE REQUIRES FAST AND EFFICIENT DELIVERY as achieved with iv injection but few know how to inject Receptor occupancy by INTRANASAL equivalent to INTRAVENOUS Naloxone Baseline Intranasal Intravenous Positive pharmacology of nasal naloxone: Rapid onset and high peak blood level 1 0 N alo x o n e P lasm a C o n cen tratio n (n g /m L ) Blood Concentration Intranasal Narcan Injectable 2 x 4 0 m g /m L IN 2 x 2 0 m g /m L IN 1 x 4 0 m g /m L IN 1 x 2 0 m g /m L IN 0.4 m g IM Phillip et al. J Pharmacol ExpTher H o u rs P o s td o s e

32 Retail Pharmacy Prescriptions for Naloxone Increase Markedly Retail prescriptions show an increase of 9520% from the 4 th quarter of 2013 to 2 nd quarter Outpatient prescribing of naloxone may complement community-based distribution and first responder access Q2010 3Q2010 1Q2011 3Q2011 1Q2012 3Q2012 1Q2013 3Q Q2014 3Q2014 Sources: Jones CM, Lurie PG, Compton WM. Am J Public Health. 2016;106(4): ; IMS Health, published Q Q2015 1Q2016 Science = Solutions

33 Medications are Effective for Opioid Use Disorder Medication Assisted Treatment (MAT) can DECREASE: Opioid use Opioid-related overdose deaths Criminal activity Infectious disease transmission And INCREASE Social functioning Retention in treatment Kakko J et al., The Lancet 2003.

34 Effective Medications for Opioid Addiction Full Agonist: Methadone (daily dosing) Partial Agonist: Buprenorphine (3-4X week, or implant) Antagonists: Naltrexone (monthly extended release) agonist antagonist no effect effect Binds to receptor but has no effect. Binds to the receptor and Prevents heroin from activates it; binding. Full agonists have maximal effect. Partial agonist have intermediate effect. Prevent Heroin from binding. Opioid Effect Full Agonist (Methadone) Partial Agonist (Buprenorphine Antagonist (Naltrexone) Log Dose Science = Solutions

35 Medications are Underused In 48 states and D.C., Opioid Abuse and Dependence Rates Exceed Buprenorphine Treatment Capacity In 2014, only 25% of opioid admissions had treatment plans that included receiving medications. 75% 25% Jones C et al., Am J Public Health MAT No MAT Treatment Episode Data Set (TEDS):

36 Science Driven Solutions: Improving Addiction Treatment Probuphine: 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 overdoses Abstinence from opioids over 12 Weeks with interim buprenorphine Abstinence with Interim Buprenorphine Lee JD, et al., Addiction 2015;100: and New EngJ Med 2016;374: Sigmon SC et al. N Engl J Med 2016.

37 Antibodies and Vaccines to Treat OUD and Prevent Overdose Heroin vaccine validated in primate model in 2017 First vaccine for fentanyl and fentanyl analogs reported in a mouse model in 2016 Reduces drug reaching the brain Protect high-risk individuals against overdose Bremer et al, 2017; Bremer et al, 2016; Janda and Treweek, 2012.

38 Non-Pharmacological Treatments for Addiction Transcranial Magnetic Stimulation (TMS) Transcranial Direct Current Simulation (tdcs) Deep Brain Stimulation (DBS) Implanted electrodes emit electrical stimulation to targeted brain region Salling and Martinez, 2016.

39 NIH Opioid Research Initiative Using Research to End the Opioid Crisis PAIN MANAGEMENT Safe, effective, non-addictive strategies OPIOID ADDICTION TREATMENT New, innovative medications and technologies Nonpharmacological Treatments (e.g. TMS) Opioid Vaccines Biomarkers For Pain Non-Opioid Analgesics Respiratory Stimulation Devices OVERDOSE REVERSAL Interventions to reduce mortality and link to treatment

40 Summary: Complex biological, developmental and social aspects of substance use and addiction suggest multipronged responses. The severity of the opioid crisis demands urgent action. Science = Solutions Advancing Addiction Science