Tue gs volkow

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General Session: Realities of Rx Drug Abuse -

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Tue gs volkow

  1. 1. Realities of Rx Drug Abuse Nora D. Volkow, M.D. Director
  2. 2. Nora Volkow has no financial relationships with proprietary entities that produce health care goods and services.
  3. 3. 1.  Investigate recent increasing trends in the misuse and abuse of Rx drugs. 2. Demonstrate the ways in which the most commonly abused Rx drug classes affect the brain and body. 3.  Outline strategies being developed and implemented that will increase awareness of the growing problem. Learning Objectives
  4. 4. Numbers in Millions  Prescription Drug Misuse/Abuse is a  Major Problem in the US Source: SAMHSA, 2012 National Survey on Drug Use and Health, 2013. 4.7 4.9 5.1 5 4.8 4.9 4.8 4.3 4.8 2.1 2.2 2.1 2.1 2 2.2 2.2 2 2.3 1.2 1.1 1.4 1.2 1.1 1.2 1.1 1 1.3 0.3 0.3 0.4 0.3 0.2 0.3 0.4 0.2 0.2 0 1 2 3 4 5 6 2004200520062007200820092010 2011 2012  Current Drug Use Rates in  Persons Ages 12+ Percent Past Year Nonmedical Use of Types of Psychotherapeutic Drugs among Persons Aged 12 or Older: 2002-2012
  5. 5. 0 100 200 300 400 500 600 700 800 900 1000 1100 0 1 2 3 4 5 hr Time After Amphetamine %ofBasalRelease AMPHETAMINE 0 50 100 150 200 0 60 120 180 Time (min) %ofBasalRelease Empty Box Feeding Di Chiara et al. FOOD VTA/SN nucleus accumbens frontal cortex These prescription drugs, like other drugs of abuse (cocaine, heroin, marijuana) raise brain dopamine levels Dopamine Neurotransmission Why Do People Abuse Prescription Drugs? Di Chiara et al.
  6. 6. Opioids: Examples: OxyContin, Vicodin Attach to opioid receptors in the brain and spinal cord, blocking the transmission of pain messages and causing an increase in the activity of dopamine How They Work… •  Postsurgical pain relief •  Management of acute or chronic pain •  Relief of coughs and diarrhea Opioids are Generally Prescribed for: Amydala (reward) NAc (reward) Thalamus (pain)
  7. 7. •  Expectation of Drug Effects Expectation of clinical benefits vs euphoria high •  Context of Administration School, clinic, home vs bar, discotheque •  Dose and Frequency of Dosing Lower, fixed regimes vs higher, escalating use •  Route of Administration Oral vs injection, smoking, snorting What is the Difference Between Therapeutic Use and Abuse?
  8. 8. Rewarding Effects of Drugs Depend on How Fast they Get into the Brain Reward Reward 0 20 40 60 80 100 0 20 40 60 80 100 0 10 20 30 40 50 60 70 80 %Peak [11C]Cocaine in brain Time (min) [11C]Ritalin in brain 0 10 20 30 40 50 60 70 80 0 0.01 0.02 0.03 0.04 0.05 0.06 0 20 40 60 80 100 120 Time (minutes) 0 0.01 0.02 0.03 0.04 0.05 0.06 UptakeinStriatum(%/cc) 0 0.0005 0.001 0.0015 0.002 0.0025 0.003 0.0035 0 20 40 60 80 100 120 UptakeinStriatum(nCi/cc) Time (minutes) iv cocaine iv Ritalin oral Ritalin 0 20 40 60 80 100 120 Time (minutes) Fast!!"Fast!!" Slow!!" Cocaine (iv) and Ritalin (iv) are rewarding but Ritalin (oral) is not. The slow brain uptake of oral Ritalin allows treatment without reward Solanto MV. Behav Brain Res 1998; 94:127–152. Fowler JS et al., Nuc Med Bio 2001; 28(5): 561-572. Volkow ND and Swanson JM. Am J Psychiatry 2003;160: 1909-1918.
  9. 9. Source: SAMHSA Treatment Episode Data Set (TEDS), 2000-2010 28,326 37,649 45,882 52,664 60,824 71,048 82,359 98,386 122,185 142,124 157,171 0 20,000 40,000 60,000 80,000 100,000 120,000 140,000 160,000 180,000 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 12 10 8 6 4 2 0 1990 1992 1994 1996 1998 2000 2002 2004 2006 2008 *Deaths  are  those  for  which  poisoning  by  drugs  (illicit,  prescrip9on,  and    over-­‐the-­‐counter)  was  the  underlying  cause. National Vital Statistics System. Drug Overdose Death Rates by State 2008. 100 people die from drug overdoses every day in the US CDC Vital Signs, July 2013.
  10. 10. Primary Substance of Abuse (Other Than Alcohol**) at Admission to U.S. State Licensed or Certified Substance Abuse Treatment Facilities, Ages 12 and Older Adapted by CESAR from OAS, SAMHSA, Treatment Episode Dataset (TEDS) Highlights—2011, National Admissions to Substance Abuse Treatment Services, 2013. PercentageofAllAdmissions 20 16 12 8 4 0 1992 1994 1996 1998 2000 2002 2004 2006 2008 2010 Prevalence Of Narcotics Involvement In Drivers Who Died Within 1 Hour Of A Crash Fatality Analysis Reporting System, Selected States, 1999–2010 Brady JE and Li G Am. J. Epidemiol. 2014. PositiveforNarcotics,% 12 10 8 6 4 2 0 1.8% 5.4% P<0.0001 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 1999
  11. 11. Past  Month  &Past  Year  Heroin     Use  Among  Persons     Aged  12  or  Older:  2002-­‐2012   Source:    SAMHSA,  2012  Na2onal  Survey   on  Drug  Use  and  Health,  2013.   404   314   398   379   560   373   455   582   621   620   669   166   119   166   136   339   161   213   193   239   281   335   0   100   200   300   400   500   600   700   800   Numbers  in  Thousands   Past  Year   Past  Month   HepaHHs  C  Virus  Among    Adolescents  &Young  Adults     Has  Increased  in  Recent  Years     Incidence  of  acute  hepaHHs  C  by  age  group   –  U.S.,  2000-­‐2011   0 0.5 1 1.5 2 2.5 3 Reportedcases/100,000population 0–19 yrs 20–29 yrs 30–39 yrs 40–49 yrs 50–59 yrs ≥60 yrs Source: National Notifiable Diseases Surveillance System (NNDSS), CDC YEAR  
  12. 12. Opioid Prescriptions Dispensed by U.S. Retail Pharmacies, 1991-2012 0 1 2 3 4 5 6 7 8 199920002001200220032004200520062007200820092010 Rate Year Opioid Sales KG/10,000 Opioid Deaths/100,000 Opioid Treatment Admissions/10,000 CDC National Vital Statistics System, SAMHSA Treatment Episode Data Set, DEA’s Automation of Reports and Consolidated Orders System.) Opioid sales increases in US parallel increases in opioid OD & Tx admission IMS Health, Vector One: National , Years 1991 to 2011, Data Extracted 2012 IMS Health, National Prescription Audit, Years 2012 & 2013, Data Extracted 2014
  13. 13. Source of Prescription Narcotics Among Those who Used in the Past Year, 12th Grade* 0 20 40 60 80 100 *Categories not mutually exclusive SOURCE: University of Michigan, 2013 Monitoring the Future Study Internet Other   Took from friend/ relative   Bought from dealer/ stranger Given by friend/ relative   Rx Bought from friend/ relative Source of Prescription Drugs Among Past Year Users Aged 12 or Older (how they obtained the drugs they most recently used nonmedically) Source: 2012 National Survey on Drug Use and Health, SAMHSA 2013. 2011 to 2012
  14. 14. Opioid Prescriptions by Age 2 6 19 30 159 - 20 40 60 80 100 120 140 160 180 - 5 10 15 20 25 30 35 2002 2006 2009 2012 No.ofPrescriptions,Age40+(millions) No.ofPrescriptions(millions) 0 to 9 10 to 19 20 to 29 30 to 39 40+ IMS Health, Vector One® National Opioids Overdose Death by Age Group, US, 2008 Rateper100,000 Paulozzi LJ, J Safety Res 2012; 43(4): 283-289.
  15. 15. Jones, CM et al. JAMA, February 20, 2013; 309(7): 657-659. PERCENT Drug Involvement in Pharmaceutical Overdose Deaths Opioid Analgesic Involvement in Deaths for Specific Drugs Specific Drug Involvement in Pharmaceutical Overdose Deaths USA, 2010 75.2 7.8 29.4 1.3 17.6 6.1 0.1 100 65.5 77.2 50 57.6 58 54.2 0 20 40 60 80 100 120 Opioid Analgesics Antiepileptic & Antiparkinsonism Drugs Benzodiazepines Barbiturates Antidepressants Antipsychotic & Neuroleptic Drugs Other Psychotropic Drugs
  16. 16. Medications for Opioid Addiction effect no effect agonist antagonist an agonist drug has an active site of similar shape to the endogenous ligand so binds to the receptor and produces the same effect an antagonist drug is close enough in shape to bind to the receptor but not close enough to produce an effect. It also takes up receptor space and so prevents the endogenous ligand from binding OpioidEffect Full Agonist (Methadone) Partial Agonist (Buprenorphine) Antagonist (Naloxone) Log Dose Source: SAMHSA, 2012 National Survey on Drug Use and Health, 2013.
  17. 17. Opioid Agonist Treatments Decreased Heroin Overdose Deaths Baltimore, Maryland, 1995-2009 Schwartz RP et al., Am J Public Health 2013;1 03: 917-922. OverdoseDeaths,No. PatientsTreated,No. Heroin overdoses Buprenorphine patients Methadone patients
  18. 18. Retention In Methadone Maintenance Drug Tx NS after adjusting for demographics, treatment agencies, other drug use, public assistance type, medical, psychiatric, social, legal and familial factors. 0 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6 1.8 2 PTOP Heroin Treatment for Addiction to Opioid Medications Prescription Opioid Abusers can be treated at MMT facilities at least as effectively as heroin users in terms of treatment retention. ODDSRATIO 6.6 49.2 8.6 0 10 20 30 40 50 60 Phase 1 Phase 2 After Taper %ofPatientsWithSuccessfulOutcomes Brief and Extended Buprenorphine-Naloxone Tx for Rx Opioid Dependence (Brief) (Extended) Weiss RD et al., Arch Gen Psych 2011; 68(12): 1238-1246. Banta-Green CJ et al., Addiction 2009; 104(5): 775-783.
  19. 19. Additional Challenge… Lack of uptake of medication-assisted treatment Addiction Specialty Programs Offering Services As % of all programs surveyed (N=345) Within adopting programs, % of eligible patients receiving Rx Opioid Tx Meds: Methadone 7.8 41.3 Buprenorphine 20.9 37.3 Tablet naltrexone 22.0 10.9 TOO FEW ARE TREATED Knudsen et al, 2011, J Addict Med; 5:21-27.
  20. 20. How Can Research Help? • Medications PAIN: Develop less abusable analgesics OD: User Friendly Naloxone ADDICTION: New Medications • mHealth Applications • Non pharmacological interventions
  21. 21. Abuse-Resistant Opioid Prodrug (i.e., Signature Therapeutics) PAIN: Less Abusable Analgesics
  22. 22. Naloxone Nasal Spray OD: User Friendly Naloxone •  AntiOp, single-dose,disposable naloxone nasal spray that combines a nasal spray device with a stable, concentrated naloxone solution •  Investigational New Drug (IND) filed in 2012 •  Product could be on the market in about 18 months •  Lightlake Therapeutics, biopharmaceutical company conducting clinical trials with intranasal naloxone for binge eating disorder is applying it towards the treatment of opioid overdose •  Clinical trials began last fall
  23. 23. mHealth for Preventing OD Wireless SENSORS Respiration Oxymeter Arrythmias ALARM Set up delivery Alert Patient Alert Third Party NALOXONE DELIVERY Automatic Patient Third party
  24. 24. ADDICTION Treatment •  Develop better, more targeted treatments •  Develop effective vaccines
  25. 25. Binding Site Capillary Blood Flow Brain Antibodies VACCINE Antibodies Can Reduce Brain Concentrations Immunotherapies for Addiction Treatment (i.e., Vaccines) Capillary Blood Flow Brain Targeting the drugs, not the receptors
  26. 26. Technologies For Invasive & Non-invasive Neuromodulation Transcranial Direct Current Simulation (tDCS) passes direct current though two electrodes on the scalp High-Definition transcranial Direct Current Stimulation (HD-tDCS) uses arrays of scalp electrode to guide current to brain structures Adapted from: Morena-Duarte I et al., Neuroimage 2014; 85(3): 1003-1013. Non-Medication Strategies For the Treatment of PAIN and ADDICTION Motor Cortex Stimulation uses electrodes positioned on the cortex Left sensory thalamusLeft periventricular gray Gray AM et al., J Pain 2014; 15(3): 283-292. Deep Brain Stimulation (DBS) Stereotaxtic implantation of electrodes that emit electrical stimulation to a targeted neuronal region Transcranial Magnetic Stimulation (TMS) uses magnets to non-invasively induce current in the brain
  27. 27. •  Responsible Prescribing and Management of Chronic Pain •  Mandatory Addiction Education in Medical, Nursing and Pharmacy Schools •  Availability of Naloxone •  Parity Tracking and Implementation •  Websites on Location and Quality of Addiction Treatment Programs Strategies that can Help Address the Dangers of Opioid Overdose and Addiction in the US
  28. 28. Mezei, L and Murinson, BB., J Pain, 12, 1199 -1208, 2011. Education on Pain in Medical Schools Number of Hours of Pain Education NumberofSchools USA (median: 7 hours) Canada (median: 14 hours) Veterinarian schools: 75 hours on pain 0-5 5-10 10-15 15-20 20-25 25-30 >30
  29. 29. •  Centers of Excellence in Pain Education (12 CoEPE) •  Consensus Workshop on Opioids for Chronic Pain ICs Involved: ORWH NIA OBSSR NINR NIDA NICHD NIDCR NIAMS NINDS NCCAM
  30. 30. Education for Healthcare Providers CME Courses developed by NIDA & Medscape Education, funded by ONDCP Safe Prescribing for Pain Managing Pain Patients Who Abuse Rx Drugs Skills and tools clinicians can use to screen for and prevent abuse in patients with pain Learn symptoms of opioid addiction & dependence in patients with chronic pain, & how to screen for, prevent, & treat such conditions
  31. 31. •  Responsible Prescribing and Management of Chronic Pain •  Mandatory Addiction Education in Medical, Nursing and Pharmacy Schools •  Availability of Naloxone •  Parity Tracking and Implementation •  Websites on Location and Quality of Addiction Treatment Programs Strategies that can Help Address the Dangers of Opioid Overdose and Addiction in the US
  32. 32. •  NIDA CoEs were established in 2007 to help fill gaps in current medical education curricula related to both illicit drugs and Rx drug abuse •  Working with NIDA, medical school faculty at the CoEs have developed a diverse portfolio of innovative curriculum resources about how to identify and treat patients struggling with drug abuse and addiction NIDA Resources for Medical Students, Resident Physicians & Faculty Centers of Excellence for Physician Information
  33. 33. Percent of Students Reporting Nonmedical Use of Vicodin in Past Year 0 5 10 15 20 02 03 04 05 06 07 08 09 10 11 12 13 Denotes significant difference between 2012 and 2013 SOURCE: University of Michigan, 2013 Monitoring the Future Study 0 5 10 15 20 02 03 04 05 06 07 08 09 10 11 12 13 Percent of Students Reporting Nonmedical Use of OxyContin in Past Year 8th Grade 10th Grade 12th Grade PREVENTION WORKS
  34. 34. Increases in Heroin Abuse as Access to Prescription Pain Relievers is Decreased Cicero TJ et al. N Engl J Med 2012;367:187-189. Growing evidence suggests that abusers of prescription opioids are shifting to heroin as prescription drugs become less available or harder to abuse For example, a recent increase in heroin use accompanied a downward trend in OxyContin abuse following the introduction of an abuse-deterrent formulation of that medication. Cicero T et al., NEJM 2013.
  35. 35. Bateman BT et al, Anesthesiology, February 2014. Prevalence of Opioid Dispensing During Pregnancy by State Opioid Use During Pregnancy (%) 6.5 -- 11.0 11.1 -- 14.0 14.1 -- 16.5 16.6 -- 20.5 20.6 -- 26.3 (Overall) and By Trimester ProportionofPregnancies 16 14 12 10 8 6 4 2 0 2005 2006 2007 2008 2009 2010 2011 Anytime in Pregnancy First Trimester Second Trimester Third Trimester Temporal Trends in Opioid Dispensing During Pregnancy
  36. 36. Ling, W. et al. JAMA 2010;304:1576-1583. IMPLANTABLE Buprenorphine – Probuphine™ Retention of Patients Through the Trial Delivers Buprenorphine for 6 Months 120 100 80 60 40 20 0 NumberofPatients 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 Week Buprenorphine Placebo 66% 31% Titan Pharmaceuticals New Medications For Addictions To Opioid Prescriptions
  37. 37. ##p<0.01, ###p<0.001, significant reduction of analgesia vs. Control/KLH group, ### p<0.001, significant reduction of analgesia vs. Control/KLH group Heroin  1  mg/kg,    s.c.   30  min   Hot Plate Test The Vaccine(s) New Heroin Vaccine(s) K.D. Janda & G.F. Koob Laboratories at TSRI
  38. 38. FDA NEWS RELEASE -- For Immediate Release: Sept. 10, 2013 The U.S. Food and Drug Administration today announced class-wide safety labeling changes and new postmarket study requirements for all extended-release and long-acting (ER/LA) opioid analgesics intended to treat pain. Safety Labeling Changes & New Postmarket Study Requirements For All Extended-Release & Long-acting (ER/LA) Opioid Analgesics •  The class-wide labeling changes include important new language to help health care professionals tailor their prescribing decisions based on a patient’s individual needs •  Based on a review of relevant literature, FDA has concluded that more data are needed regarding the serious risks of misuse, abuse, hyperalgesia, addiction, overdose, and death associated with the long-term use of ER/LA opioid analgesics and is thus requiring ER/LA opioid analgesic drug sponsors to conduct post-marketing studies and a clinical trial to assess these risks.
  39. 39. Prediction of Pain on the Basis of Data from Other Participants in Study 1. Wager TD et al. N Engl J Med 2013;368:1388-1397. Pain Signature Map, voxels in which activity reliably predicted pain fMRI-Based Neurologic Signature of Physical Pain

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