Reali&es of Addic&on Dr. Nora Volkow April 2 – 4, 2013 Omni Orlando Resort at ChampionsGate
Learning Objec&ves 1. Iden=fy recent increasing trends in the misuse and abuse of prescrip=on drugs. 2. Describe the ways in which the most commonly abused prescrip=on drug classes aﬀect the brain and body. 3. Explain strategies being developed and implemented that will increase awareness of the growing problem of addic=on.
Disclosure Statement • Dr. Nora Volkow has no ﬁnancial rela=onships with proprietary en==es that produce health care goods and services.
Numbers in Millions Prescrip&on Drug Misuse/Abuse is a Major Problem in the US Current Drug Use Rates in Persons Ages 12+ Source: SAMHSA, 2011 Na2onal Survey on Drug Use and Health`
Prevalence of Past Year Drug Use Among 12th graders2012 Monitoring the Future Study* Nonmedical useDrug Prev. Drug Prev. Tranquilizers* 5.3 Marijuana/Hashish 36.4 Hallucinogens 4.8 Small Cigars 19.9 Seda&ves* 4.5 Hookah 18.3 Salvia 4.4 Synthe=c Marijuana 11.3 OxyCon&n* 4.3 Snus 7.9 Hall other than LSD 4.0 Narco2cs o/t Heroin* 7.9 MDMA (Ecstasy) 3.8 Amphetamines* 7.9 Inhalants 2.9 Adderall* 7.6 Cocaine (any form) 2.7 Vicodin* 7.5 Ritalin* 2.6 Cough Medicine* 5.6 LSD 2.4 Categories not mutually exclusive
0100200300400500600700800900100011000 1 2 3 4 5 hrTime After Amphetamine%ofBasalReleaseAMPHETAMINE0501001502000 60 120 180Time (min)%ofBasalReleaseEmptyBox FeedingDi Chiara et al.FOODVTA/SNnucleusaccumbensfrontalcortexThese prescription drugs,like other drugs of abuse(cocaine, heroin, marijuana)raise brain dopamine levelsDopamine Neurotransmission Why Do People Abuse Prescription Drugs?
Opioids: Examples: OxyContin, VicodinAttach to opioid receptors in thebrain and spinal cord, blockingthe transmission of pain messagesand causing an increase in theactivity of dopamineHow They Work…• Postsurgical pain relief• Management of acute or chronicpain• Relief of coughs and diarrheaOpioids are Generally Prescribed for:Amydala(reward)NAc(reward)Thalamus(pain)
Similari&es Between Illicit and Prescrip&on Drugs
StimulantsEnhance brain activity by increasing the activity ofbrain excitatory chemical messengers, such asnorepinephrine and dopamine, leading to mentalstimulationExample: RitalinHow They Work…• ADHD• Narcolepsy• Depression that does notrespond to other treatments• Asthma that does notrespond to other treatmentStimulants Are Generally Prescribed For:
MethamphetamineAdderallSimilari&es Between Illicit and Prescrip&on Drugs
• Expectation of Drug EffectsExpectation of clinical benefits vs euphoria high• Context of AdministrationSchool, clinic, home vs bar, discotheque• Dose and Frequency of DosingLower, fixed regimes vs higher, escalating use• Route of AdministrationOral vs injection, smoking, snortingWhat is the Difference BetweenTherapeutic Use and Abuse?
"High" "High" 0204060801000204060801000 10 20 30 40 50 60 70 80%Peak[11C]CocaineTime (min)[11C]Methylphenidate0 10 20 30 40 50 60 70 80Rewarding Effects Depend on How Fastthe Drug Gets into the Brain
00.010.020.030.040.050.060 20 40 60 80 100 120UptakeinStriatum(%/cc)Time (minutes)00.010.020.030.040.050.06UptakeinStriatum(%/cc)00.00050.0010.00150.0020.00250.0030.00350 20 40 60 80 100 120UptakeinStriatum(nCi/cc)Time (minutes)iv cocaine iv Ritalin oral RitalinRate of Drug Uptake Into the BrainCocaine (iv) and Ritalin (iv) produce a highbut Ritalin (oral) does not.The slow brain uptake of oral Ritalinpermits effective treatment without a high.0 20 40 60 80 100 120Time (minutes)Fast!!!Fast!!! Slow!!!
Source: Volkow, ND et al., Journal of Neuroscience, 23, pp. 11461-‐11468, December 2003. Glucose Metabolism Was Greatly Increased By the Expecta2on of the Drug Unexpected MP700µmol/100g/minExpected MPIncreases in Metabolism Were About 50% Larger When MP Was Expected Than Unexpected 051015202530%ChangeUnexpected MP Expected MP Expected MP Got Placebo
What Has Raised Our AUen2on to the Problem of Prescrip2on Drug Abuse?
Source: SAMHSA Treatment Episode Data Set(TEDS), 2000-201028,32637,64945,88252,66460,82471,04882,35998,386122,185142,124157,171020,00040,00060,00080,000100,000120,000140,000160,000180,0002000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010More Than 5-Fold IncreaseIn Treatment Admissions ForPrescription PainkillersIn the Past Decade12 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, prescrip=on, and over-‐the-‐counter) was the underlying cause.Drug Overdose Death Rates in the US Have More Than Tripled since 1990 Na&onal Vital Sta&s&cs System. Drug Overdose Death Rates by State 2008. 100 people die from drug overdoses every day in the US
35,00030,00025,00020,00015,00010,0005,0000Number of ED Visits 9,0006,0003,0000Aged 5 to 11 Aged 12 to 17 Aged 18 to 25 Aged 26 to 34 Aged 35 or Older 2005 2010 3,322 3,791 2,702 3,461 2,131 8,148 1,754 6,094 2,519 7,957 Number of ED Visits 2005 2006 2007 2008 2009 2010 4,315 6,332 11,390 11,448 12,208 14,068 17,174 14,503 12,287 14,979 10,614 9,059 13,379 16,948 26,369 23,735 26,711 31,244 All Males Females Emergency Department (ED) Visits Related toStimulant MedicationsSource: SAMHSA Dawn Report:Emergency Department Visits Involving AUen2on Deﬁcit/ Hyperac2vity Disorder S2mulant Medica2ons , January 24, 2013.
Data in Several States Show That Hepatitis C VirusAmong Adolescents and Young AdultsHas Increased in Recent YearsOf cases with available risk data, injec2on drug use (IDU) was the most common risk factor for HCV transmission Although only a small number of these cases responded to further inves2ga2on….. • 92% reported opioid analgesic abuse • 89% reported heroin use • 95% used opioid analgesics before switching to heroin • During the preceding 6 months, the most frequently injected drugs were heroin (50%) and opioid analgesics (30%) CDC, MMWR, May 6, 2011/60(17); 537-541;CDC, MMWR, October 28, 2011/60(42):1457-‐1458
Number of Opioid Prescriptions Dispensed byU.S. Retail Pharmacies, Years 1991-201176 78 8086 91 96 100109120131139144151158169180192201 20221021905010015020025091929394959697989920000102030405060708091011Prescriptions(millions)IMS’s Source Prescription Audit (SPA) &Vector One®: National (VONA)Opioids Hydrocodone Oxycodone
Opioid Prescriptionsby Age261930159-20406080100120140160180-51015202530352002 2006 2009 2012No.ofPrescriptions,Age40+(millions)No.ofPrescriptions(millions)0 to 9 10 to 19 20 to 2930 to 39 40+IMS Health, Vector One® NationalOpioids OverdoseDeath by Age Group,US, 2008Rate per 100,000 Paulozzi LJ, J Safety Res 2012; 43(4):283-289.
Top Prescribers of Opioid Analgesics in2012010,000,00020,000,00030,000,00040,000,00050,000,00060,000,00020022003200420052006200720082009201020112012PrescriptionsGP/FM/DOInternal medicineDentistryOrthopedicSurgeryIMS Health, Vector One® National
Percent Source: 2010 Na2onal Survey on Drug Use and Health, SAMHSA 2011. Source of Prescrip&on Drugs (how they obtained the drugs they most recently used nonmedically) Rates averaged across 2009 and 2010
Jones, CM et al. JAMA, February 20, 2013; 309(7): 657-659.National Center for Health Statistics show drug overdose deathsincreased for the 11th consecutive year in 2010In 2010, there were 38,329 drug overdose deaths in the United States Percentage of Overdose Deaths for Speciﬁc Psychotherapeu=c and CNS Pharmaceu=cals that Involved a Single Drug Class, US, 2010 PsychotherapeuticandCNSPharmaceuticals,%Opioid Analgesics (n=16,651) An&epilep&c & An&parkinsonism Drugs (n=1,717) Benzodizepines (n=6,497) Barbiturates (n=296) An&depressants (n=3,889) An&psycho&c & Neurolep&c Drugs (n=1,351) Other Psychotropic Drugs (n=24) 35302520151050
Jones, CM et al. JAMA, February 20, 2013; 309(7): 657-659.PERCENT Drug Involvement in Pharmaceu=cal Overdose Deaths Opioid Analgesic Involvement in Deaths for Speciﬁc Drugs Speciﬁc Drug Involvement in Pharmaceu&cal Overdose Deaths USA, 2010 75.27.829.41.3220.127.116.11065.577.25057.6 5854.2020406080100120
How to Minimize the Diversion andAbuse of Prescription MedicationsEngage the Healthcare System
Doctors Need to Know…What Opioid Prescriptions Have Been Given toTheir Patients By Other Doctors or PractitionersThis information should be:1) included in the patients’electronic health care records2) accessible through aPrescription Drug MonitoringProgram (PDMP) that providesimmediate information and cancross-reference across States
Mezei, L and Murinson, BB., J Pain, 12, 1199 -‐1208, 2011. Education on Pain in Medical SchoolsNumber of Hours of Pain EducationNumber of Schools USA (median: 7 hours)Canada (median: 14 hours)Veterinarian schools:75 hours on pain0-5 5-10 10-15 15-20 20-25 25-30 >30
• Centers of Excellence in Pain Education (12 CoEPE)• Consensus Workshop on Opioidsfor Chronic PainICs Involved:ORWH NIAOBSSR NINRNIDA NICHDNIDCR NIAMSNINDS NCCAM
• Efficacy of opioids for treating chronic pain• How to administer opioids for optimal efficacy and minimaladverse effects• Risks for addiction• Populations differences• What training is available (other than offered by industry) forteaching how and what type of opioids should be used inmanaging chronic pain?• What research directions need to be pursued to determine bestapproaches for managing chronic pain with opioids?• For research gaps, what are research priorities?Consensus Workshop: Opioids for Chronic Pain
Prevention Strategies – Public EducationCME Courses developed by NIDA & Medscape Education, funded by ONDCPSafe Prescribing for Pain Managing Pain Pa&ents Who Abuse Rx Drugs Skills and tools clinicians can use to screen for and prevent abuse in pa7ents with pain Learn symptoms of opioid addic7on and dependence in pa7ents with chronic pain, and how to screen for, prevent and treat such condi7ons
Pain Medica&ons • Develop medications with slower abusepotential including drugs that don’t crossBBB (i.e., CBR2 agonist)• Develop slow release formulations (lowdose and long duration)• Develop novel formulations toreduce abuse liability includingmixture formulations (e.g., naloxoneand buprenorphine)00.00050.0010.00150.0020.00250.0030.00350 20 40 60 80 100120UptakeinStriatum(nCi/cc)Time (minutes)Slow!!!
Prevention Strategies – Overdose Intervention• Naloxone Distribution for opioidoverdose victims. The potential fordirect intervention to save lives.• Naloxone Nasal Spray DevelopmentNeedle-free, unit-dose, ready-to-useopioid overdose antidoteNIDA STTR Grantee – An7Op, Inc., Daniel Wermeling, CEO Contact: E-‐mail: email@example.com, Tel: 859-‐221-‐4138
Treatment of Addiction to Prescription OpioidsBuprenorphineCurrently 19,000 physicians are certiﬁed to prescribe buprenorphine (Source: CSAT Buprenorphine Information Center) Targets the same opioid receptors asmorphine (mu) but its much less potent,has a much longer half life and does notproduce the same high as heroin ormorphine
Universal Drug Abuse PreventionMay Reduce Prescription Drug MisuseSpoth et al., Addiction 2008;103(7):1160-1168.Spoth, et al., AJPM 2011;40(4):440-447For 100 young adultsin general populationstarting Rx abuse,only 35 young adultsfrom an interventioncommunity started.Overall, three studiesnow suggest theimpact of universalprevention onprescription drugabuse.
Numbers in Thousands Source: 2011 Na2onal Survey on Drug Use and Health, SAMHSA, 2012. Large Number of Past Year Initiates of Pharmaceuticals:Persons Aged 12 or Older, 2011MarijuanaPain RelieversTranquilizersEcstasyInhalantsCocaineStimulantsLSDHeroinSedativesPCP
Overdoses of prescription painkillershave more than tripled in the past 20years, killing more than 15,500 people inthe US in 2009For every overdose death from prescrip=on painkillers there are treatment admissions for abuse emergency department visits for misuse or abuse people who abuse or are dependent people who take prescrip=on painkillers for non-‐medical use 10 32 130 825