1 Treatment of Opioid Addiction Miriam Komaromy, MD Associate Director, Project ECHO University of New Mexico Health Sciences Center
2 Why does the human brain become addicted? Why can we only become addicted to some substances?
3 What is addiction?
5 What is addiction? Physical Dependence Withdrawal if discontinued Used as needed to control pain Tolerance Slowly increasing need over time Further increased need in response to increased pain Generally taken as directed Addiction Withdrawal if discontinued Used for the purpose of becoming euphoric Compulsive, escalating use Continued use despite negative consequences Legal, medical, psychological, and social impact
6 Why do we find some things pleasurable, and not others?
7 The Reward Pathway A particular pathway in the brain is activated by all of the activities that we find pleasurable Food, water and sex; appetites Interpersonal relationships, spirituality, exercise, art, music, beauty The common reward pathway in the brain for all pleasurable activities involves the neurotransmitter Dopamine
8 The Lizard Brain
9 The drugs that we can become addicted to are those that hijack the natural pleasure circuitry of the brain
10 All addictive drugs act via dopaminergic pathways Dopamine
11 How have scientists sorted out how the addicted brain works?
12 It turns out that rats are remarkably similar to humans..
13 Experimental system for studying addiction in rats The (few) drugs that are self-administered by a rat are exactly the same as those that humans will self-administer Wise RA, Biological Psychiatry 2002
14 Rat model of addiction Rat is given a microinjection of an addictive drug into the reward pathway, and can repeat the experience by pushing a lever Initial random lever-pushing quickly becomes compulsive When rat receives drug (cocaine) every time it pushes the lever, it will starve to death or die of thirst rather than leave the lever to go into another part of the cage to eat or drink Routtenberg, 1965
15 Measuring intensity of addictive potential When rat is only rewarded in a progressive ratio (every 2 nd, 4 th, 8 th push, etc), eventually it reaches a point where it will walk away from the lever (breakpoint) Correlates with addiction potential of drugs in humans For some drugs, the breakpoint is in the 10,000 range
16 What about opioid addiction?
17 Picture of opioid addiction: heroin
18 Picture of opioid addiction: pain pills
19 Number of deaths Unintentional overdose deaths involving opioid analgesics now exceed the sum of deaths involving heroin or cocaine 14,000 12,000 Opioid analgesic 10,000 8,000 Cocaine 6,000 4,000 Heroin 2,000 0 '99 '00 '01 '02 '03 '04 '05 '06 07 Source: National Vital Statistics system, multiple cause of death dataset, Len P aulozzi, CDC
20 Unintentional overdose deaths involving opioid analgesics parallel per capita sales of opioid analgesics in morphine equivalents by year, U.S., Deaths As of 2007, Hydrocodone is the most prescribed Drug in the US, with 117 million prescriptions in 2007 Opioid sales (mg/person) '97 '98 '99 '00 '01 '02 '03 '04 '05 '06 '07 * Source: National Vital Statistics System, multiple cause of death dataset, and DEA ARCOS * 2007 opioid sales figure is preliminary. 5
21 Age Adjusted Rates per 100,000 persons 30.0 Drug Overdose Death Rates, New Mexico and United States, NM US 0.0 Source: : CDC Wonder; 2009 US: NCHS; NM: BVRHS.
22 Age-adjusted rates per 100,000 persons Leading Causes of Unintentional Injury Death, New Mexico, Poisoning Motor Vehicle, Traffic Falls Source: New Mexico Vital Records and Health Statistics.
23 What role do dentists play? Although most Oral-Maxillofacial Surgeons state that ibuprofen is most effective analgesic after 3 rd molar extraction, 85% also prescribe an opioid Average 20 tablets hydrocodone/apap Some prescribe much more Estimate: 61 million opioid tablets prescribed to people whose average age is 20 ER study: 81% of patients presenting to ER with dental pain received opioid prescription Denisco, JADA 2011 Moore, Gen Dent 2006 Hocker, NC Med J 2012
24 What can dentists do about opioid overprescribing? Prescribe opioids less often, in lower quantities Instruct patients to call if inadequate analgesia Warn patients of risk of opioid addiction Instruct patients to secure opioid tablets, and discard unused opioids Consider screening for problems with abuse/addiction Denisco, JADA 2011
25 Most effective treatment is Medication Assisted Treatment
26 Why do we need new ways of treating opiate addiction? Detox has no impact on long-term outcomes Only 200,000 patients on methadone for addiction treatment Treatment access is limited SAMHSA Nat Survey Drug Use and Health 2006
27 Treatment of Opiate Addiction is Effective Decreases death rate 1 Decreases HIV infection 2-3 Opioid agonist treatment of injection drug users decreased HIV incidence by 54% 2 Decreases crime 4 1. Kreek J, Subst Abuse Treatment 2002; Gueve PN, Addiction MacArthur, BMJ, Metzgar, Public Health Reports Gerstein DR et al, CALDATA General Report, CA Dept of Alcohol and Drug Programs, 1994
28 Opiate agonists: Methadone & Buprenorphine
29 Methadone 1 Causes a 2/3 reduction in heroin use; can also be used for pain pill addiction Crime decreased 84%, drug selling decreased 86% Hospitalization decreased 58% Highly cost-effective for society: savings $3-4 for every dollar spent on treatment 1 Gerstein DR et al, CALDATA General Report, CA Dept of Alcohol and Drug Programs, 1994
30 Methadone Clinic Effective for many patients Structure of treatment setting can be helpful Now paid for by NM Medicaid
31 Problems with methadone: structural factors Access; can only be prescribed in a federallyregulated methadone clinic when used for addiction Cost ($5-13 per day; some public support) Directly observed therapy Exposure to other drug users 1 1. Salsitz, Mt Sinai J of Medicine, 2000
32 Problems with methadone: drug factors Sedation, high Difficult detox High doses required to be effective Overdose potential diversion Stigma
33 What is buprenorphine (Suboxone)? Newer medication (2002) for Medication- Assisted Treatment for opiate addiction(heroin and pain pills) 1 Detox or maintenance About as effective as methadone 2, 3 Several advantages over methadone 1 TIP Series # 40, SAMHSA, Mattick RP, Cochrane Database Systemic Review Soeffing, JSAT, 2009
34 Buprenorphine vs Methadone Like Methadone Reduces IDU Retains pt in treatment Decreases craving Stops withdrawal Costs $ 5-13 per day Unlike Methadone. Low potential for OD Prescribed in MD office No sedation Easy taper/detox
35 Suboxone 8 mg tablets Also available as a fastdissolving sublingual film Two new generic formulations of buprenorphine/ naloxone recently approved Cost will drop rapidly
36 Trial of buprenorphine 40 Heroin addicts Buprenorphine 8mg/day vs taper + placebo All received counseling, groups Followed for 1 year Buprenor -phine Placebo Retained at 1 yr 70% 0 % died 0 20% Kakko et al, Lancet 2003
38 How effective is buprenorphine for opiate addiction treatment? Author, Journal Year n Setting % still participating in treatment Fudala, NEJM Multicenter research trial Alford, JGIM Acad med Ctr/ Community clinic; ½ patients homeless; nurse case mgr Mintzer, Ann Fam Med Cunningham, Fam Med Soeffing, J Subst Abuse primary care practices Urban community health center Urban academic health center 6 months 12 months 6 months 3 months 12 months
39 Why is overdose potential low with buprenorphine? Respiratory suppression, death Agonist: Methadone, Heroin, etc. Opioid Effects Partial Agonist: Buprenorphine Antagonist: Naltrexone Log dose
40 What about diversion of buprenorphine? When patients abuse a drug, they usually crush it and inject it Buprenorphine is sold as Suboxone, a pill that contains both buprenorphine and naloxone (Narcan ) When taken under the tongue, the naloxone is not absorbed and so is not active When injected, the naloxone is active and causes withdrawal (if the patient is opiate-dependent) Decreases, but does not prevent, misuse
41 What s diversion all about? 2010 Harvard study of people seeking treatment concluded: illicit buprenorphine rarely represents an attempt to attain euphoria. Rather, illicit use is associated with attempted self-treatment of symptoms of opioid dependence, pain, and depression. Interestingly, although absolute numbers of diverted tablets are increasing, diversion has remained relatively steady as a proportion of prescribed tablets Schuman-Olivier, JSAT, 2010 Johanson, Drug Alcohol Dep, 2012
42 Survey of opioid addicts 76% 74% 72% 70% 68% 66% 64% 62% 60% 58% Treat opioid withdrawal symptoms Try to stop using other opioids Unable to afford treatment Bazazi, J Addict Med 2011
43 Buprenorphine administrative issues 8 hours of training required Only physicians may prescribed Maximum 30 simultaneous patients in year one, 100 patients thereafter Medication costs about $450 per month, covered by Medicaid with PA Far too few physicians prescribe in NM
44 Buprenorphine is an effective treatment that can help your patients who are dependent on pain pills or other opiates.
45 Non-opioid treatment options for opioid addiction
46 Oral naltrexone Opioid blocker; does not decrease craving Minimally effective for treating opioid addiction 1 Problem is non-adherence Effective in selected highly-monitored, highly motivated patients: 94% of health care professionals had long term sobriety 1. Minozzi, Cochrane Database Syst Rev Roth, J Subst Abuse Treatment 1997
47 Injectable Naltrxone FDA approved recently for opioid addiction treatment; Vivitrol, previously approved for treatment of alcohol addiction No head-to-head studies vs buprenorphine; NIDA trial pending Small amount of promising data on efficacy Cost: $1099 per injection 1. Krupitsky, Lancet, Lobmaier, Cochrane Syst Rev Comer, Arch Gen Psych 2007
48 Trial of injectable naltrexone vs Placebo for 24 weeks 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% fully abstinent x 24 weeks % of weeks abstinent Data from treatment completers Injectable naltrexone Placebo Krupitsky, Lancet, 2011
49 Injectable naltrexone efficacy Studied in Russia, against placebo Sponsored by manufacturer Initiated during inpatient detox/rehab 24 wk trial with monthly Vivitrol vs placebo, and 2x per month counseling 54% did not complete trial
50 Injectable Naltrexone offers great promise, but more data are needed to understand risks & benefits as well as barriers in outpatient practice
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