MARRCH 2008 Minnesota Society of Addiction Medicine Presents Addiction as a Brain Disease Gavin Bart, MD Charles Reznikoff, MD Steven Fu, MD, MSCE David Frenz, MD, MS October 22, 2008
Schedule 10:00-12:00 Gavin Bart Introduction Addiction as a Brain Disease: opiate dependence 1:00-1:40 Charels Reznikoff Marijuana: psychiatric and medical consequences 1:50-2:30 Steven Fu Smoking cessation in alcohol dependence 3:00-3:40 David Frenz Alcohol dependence treatment Benzodiazepine dependence treatment 3:50-4:30 Gavin Bart Ending Q&A session
A Lesson in Civics September 29 House rejects bailout October 1 Senate passes bailout October 3 bailout signed into law as Emergency Economic Stabilization Act of 2008
Article 1 Section 7. All bills for raising revenue shall originate in the House of Representatives; but the Senate may propose or concur with amendments as on other Bills.
What the Senate Passed Paul Wellstone and Pete Domenici Mental Health Parity and Addiction Equity Act of 2008 Bailout was an amendment
The Costs Bailout bill $700,000,000,000 Alcohol, tobacco, and other drugs $500,000,000,000 Per year What is the real bailout?
What does it mean for you? Equal mental health and addiction coverage No hospitalization limits No limited sessions Equal copays Pre-defined list of covered diseases Who is a qualified provider? Economic bottom-line gets covered Evidence-based practice Results will be expected and tracked
Treating Addiction as a Brain Disease The Case of Opiate Dependence If addiction is a disease then, Addiction must be treated like one
The Burden of Addiction 12.4% of all deaths in the world are related to substance use When does death occur? >50% early life for drugs 65% before age 60 for alcohol 70% after age 60 for tobacco WHO 2002
1-Year Prevalence of Drug Use National Survey on Drug Use and Health 2006 Alcohol Use Alcohol Dependence 1:20 Cocaine Use Cocaine Dependence 1:5 Heroin Use Heroin Dependence 1:2 Illicit Use of Pain Medication Pain Medication Dependence 1:12 ~ 162 million ~ 6 million ~ 0.55 million ~ 12 million SAMHSA, Office of Applied Studies, National Survey on Drug Use and Health, 2004 and 2005
A Growing Concern: Illicit Use of Prescription Opioids 20% Ages 18 to 25 15% 10% Ages 12 to 17 5% 0% 65 70 75 80 85 90 95 00 The New York Times Saturday, October 18, 2003 source: Food and Drug Administration NSDUH 2004
National Survey on Drug Use and Health: Minnesota Estimated Numbers of Persons Aged 12 or Older Needing But Not Receiving Treatment in the Past Year: Illicit Drugs: 104,000 Alcohol: 354,000 SAMHSA, Office of Applied Studies, National Survey on Drug Use and Health, 2004 and 2005
Kreek et al., 2000 Factors Contributing to Addiction use of the drug of abuse essential (100%) Genetic Environmental Drug-Induced Effects
Continuum of Risk
Kaij 1957; Kendler et al. 1997 Twin Studies of Alcoholism 1957 Kaij Identical twins had similar severity 1997 Kendler et al. 8935 Swedish twin-pairs born 1902-1949 Concordance greater in MZ than DZ
Adoption and Alcoholism 4x risk if biological parent alcoholic 9x risk for moderate alcohol abuse if biological father had it Cloninger et al. 1981
Bipolar disorder Asthma Schizophrenia 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 Heritability Alcohol dep. HTN CAD Cocaine dep. DM2 Opiate dep. MDD
Environment
Dopamine D2 Receptor in Monkeys Morgan et al., 2002
Social Rank and Effect of Prolonged Cocaine Use on Dopamine D2 Receptor Cocaine use Cocaine abstinence Czoty et al., 2004; Nader and Czoty 2005
Pharmacology
Impact of Short-Acting Heroin As Used on a Chronic Basis in Humans Functional State (Heroin) "High" "Straight" "Sick" (overdose) AM PM AM PM AM Days Dole, Nyswander and Kreek, 1966
Disruptions Induced by the On-Off of Drugs of Abuse levels of gene expression receptor mediated events physiology behaviors
Acute Opiate Effects on Endocrine Function in Humans Inhibition of release of ACTH Altered release of cortisol Inhibition of release of LH Lowered levels of testosterone Increased release of vasopressin Increased release of prolactin
Goals and Rationale for Specific Pharmacotherapy for an Addiction 1. Prevent withdrawal symptoms 2. Reduce drug craving 3. Normalize any physiological functions 4. Target treatment agent to specific site of action affected by drug of abuse
Characteristics of an Effective Addiction Medication Orally effective Slow onset of action Long duration of action Slow offset of action
Heroin versus Methadone versus Buprenorphine* Heroin Methadone Buprenorphine Route intravenous oral sublingual Onset immediate 30 minutes 30 minutes Duration 3 6 hrs 24 36 hrs 36 hours Euphoria 1 2 hrs none none Withdrawal after 4 hrs after 24 hrs after 36 hours * effects of high dosages in tolerant individuals
Impact of Short-Acting Heroin versus Long-Acting Methadone Administered
Steady-State Methadone Administration in the Rat No Disruption of Stress Response Related Gene Expression (mrna Levels) CRF mrna CRF- R1 Receptor mrna POMC mrna Mu opioid receptor mrna Unterwald et al., 1995 ; Zhou et al., 1996;
Stable Dosing Reduce/eliminate withdrawal Reduce/eliminate craving Restore physical function Minimize side-effects No such thing as high or low doses only doses that work Generally between 80-120 mg/day Not all issues are solved by changing dose
HFA Methadone Clinic 100 Opiate % Utox positive 75 50 25 0 0 10 20 30 40 50 Week
Kaplan-Meier Curve of Cumulative Retention in Treatment Remaining in treatment (nr) 20 15 10 5 Control Buprenorphine 0 0 50 100 150 200 250 300 350 Treatment duration (days) Kakko et al. 2003
Buprenorphine Clinical Trials Buprenorphine superior to placebo Buprenorphine high dose v methadone high dose Equivalency Buprenorphine low dose v methadone low dose Equivalency Buprenorphine flex dose v methadone flex dose Equivalency Mattick et al. 2003
Breen et al. 2003; Gandhi et al. 2003; Lintzeris et al 2002; Umbricht et al. 1999 Buprenorphine for Detoxification Withdrawal symptoms alleviated Not clearly easier than methadone Both buprenorphine and methadone taper associated with relapse rates >70% 90% of HFA buprenorphine maintenance patients failed previous short-term buprenorphine detoxification Maintenance is the model
Drug Use in Long-Term Methadone Maintained Patients v. Heroin Addicts Ongoing drug of abuse: Alcohol abuse Cocaine use Benzodiazepine use Marijuana use Active Parenteral Heroin Addicts (n=56) 64% 88% 18% 60% Long-Term Methadone Maintained Former Heroin Addicts (n=110) 13% 17% 7% 18% Novick et al., Drug and Alc. Depend., 33:235, 1993
Comparison of Relapse Rates Between Drug Addiction and Other Chronic Illnesses SOURCE: McLellan et al, JAMA 284: 1698-1695, 2000. 100 90 80 70 60 50 40 30 20 10 0 Percent of patients who relapse 40-60% 30-50% 50-70% 50-70% Drug Addiction Type I Diabetes Hypertension Asthma Relapse rates for drug-addicted patients are compared with rates for those suffering from diabetes, hypertension and asthma. Relapse is common and similar across these illnesses (as is adherence to medication). Thus, drug addiction should be treated like any other chronic illness, with relapse serving as a trigger for renewed intervention.
Natural history of opiate addiction Lexington study of opiate addicts admitted 1936-1940 (n=4766) 6 month to 5 year follow up after discharge Voluntary patients (n=272) Intention to treat: 82.9% failed 17.1% met treatment goal 19.3% lost to follow up 10.8% dead 52.8% relapse Average time to relapse 25.1 months 17.1% abstinent Pescor, 1943
Natural history of opiate addiction Lexington study of New York City addicts admitted in 1952 (n=100) 20 year follow up Intention to treat 68% failed 32% met treatment goal 10% lost to follow up 23% dead 25% relapse Average 7 hospitalizations, 8 imprisonments, average 4 years institutionalized Voluntary abstinence rate 1952-1964: 3% Voluntary abstinence rate 1964-1970: 67% Vaillant 1973
Natural History of Opiate Addiction California study of 581 male heroin addicts admitted 1962-1964 (n=581) Drug overdose 21.6% Liver disease 15.2% Murder Suicide 19.5% Accident Hser et al. 2001
Natural History of Opiate Addiction Best abstinence-based treatment available 83% failed within 2 years Short-term methadone 80% failed within 2 years Gradual taper off of methadone 3.5 x death in first 2 years compared to those kept on methadone Pescor, 1943; Vaillant 1973; Woody 2007
Addiction s Other Diseases Early treatment reduces hepatitis C and HIV risk 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% HCV HIV-1 <20 20-29 30-39 40-49 >50 Age at admission into MMT (years) Piccolo et al. 2002
Opiate Addiction Treatment Methadone Buprenorphine Idaho Montana North Dakota South Dakota
Methadone Myths Does not eat your bones Does not rot your teeth Methadone is a legal addiction Addiction is maladaptive behavior Methadone maintenance restores behavior Methadone withdrawal is the worst Methadone makes you dumb Functional cognitive ability remains intact
A functional patient on methadone
Cost of Opiate Addiction versus Treatment Annual Cost per Person $314,000-$350,000 Liver transplantation $100,000-$200,000 Last 2 years of AIDS $100,000 Street or blue collar crime by a cocaine or heroin addict $30,000-$70,000 Prison (state or federal) $20,000-$100,000 Residential drug-free programs $4,055 at HCMC Methadone maintenance treatment program with onsite counseling and access to medical and psychiatric care
Methadone Maintenance Treatment Effect on Criminality Dole et al. 1968 Dole et al. 1968
Methadone and Prisoners 197 Prerelease Counseling +referral Counseling + transfer Counseling + methadone 8% entered treatment 50% entered treatment 69% entered treatment 29% reincarcerated 33% reincarcerated 13% reincarcerated
Components of Comprehensive Drug Abuse Treatment HOUSING/ TRANSPORTATION FAMILY SERVICES CHILD CARE SERVICES INTAKE PROCESSING/ ASSESSMENT VOCATIONAL SERVICES MENTAL HEALTH SERVICES BEHAVIORAL THERAPY & COUNSELING TREATMENT PLAN SUBSTANCE USE MONITORING CLINICAL AND CASE MANAGEMENT PHARMACOTHERAPY SELF-HELP/PEER SUPPORT GROUPS FINANCIAL SERVICES CONTINUING CARE MEDICAL SERVICES LEGAL SERVICES AIDS/HIV SERVICES EDUCATIONAL SERVICES NIDA, 2000
Accessing Methadone Treatment Placement via Rule 25 Dual placement allowed Most 3 rd party payors cover Medicaid does not cover
Accessing Methadone Treatment Access available within 14 days Emergency/priority placement for Pregnancy HIV positive Medically ill CSAT: http://csat.samhsa.gov/ DHS website http://mhcpproviderdirectory.dhs.state.mn.us/
Adequate Dosing It is never a matter of medication or behavioral change
Standards of Care What is our standard of care?