Addiction as a Neuropsychiatric Medical Condition

Transcription

1 Addiction as a Neuropsychiatric Medical Condition Wilson M. Compton, M.D., M.P.E. Director, Division of Epidemiology, Services and Prevention Research National Institute on Drug Abuse 5 November 2009

2 Summary Addressing addiction as a brain disease allows it to be embedded within the medical/health care system: Promising Practice: Screening and Brief Intervention or Referral to Treatments (SBIRT). Improving development of medications. Blending science and services to address practice relevant research.

3 Why focus on drug use in medical/health care system? Drug use has wide ranging health and social consequences. Cardiovascular disease, stroke, cancer, HIV/AIDS, anxiety, depression, sleep problems, as well as financial difficulties and legal, work, and family problems can all result from or be exacerbated by drug use. Occurrence of Medical Conditions in Diagnosed Substance Abusers Source: Mertens JR et al, Arch Intern Med 163: , 2003

4 Why focus on drug use in medical/health care system? Many patients don t feel they need treatment and therefore won t seek it on their own. Did Not Feel They Needed Treatment (19.8 million) Felt They Needed Treatment and Did Make an Effort (233,000) 20.8 Million in US Needing But Not Receiving Treatment for Illicit Drug or Alcohol Use (Source: NSDUH, 2008) Physicians don t routinely screen for drug use. Don t know what to do No effective treatment Not medical problem No time Felt They Needed Treatment and Did Not Make an Effort (766,000)

5 Embedding Addiction Services in Medical/Health Care System Promising Practice: Screening and Brief Intervention or Referral to Treatments (SBIRT). Improving development of medications. Blending science and services to address practice relevant research.

6 Alcohol and Tobacco: SBIRT model widely accepted Tobacco Alcohol

7 Evidence for Illicit Drugs

8 60% 40% 20% Brief motivational intervention reduces 6 mo. cocaine and heroin use Abstinence Among Those Screening Positive for At Baseline (N=1175), comparing those who did and did not receive peer delivered, brief (~20 minutes) intervention with booster phone call (~5 minutes) 10 days later 22.3% p < % 40.2% 30.6% Intervention Control 0% Cocaine Opioids Bernstein et al. Drug and Alcohol Dependence 2005

9 WHO ASSIST Phase III Project WHO ASSIST Phase III Technical Report, 2008 International randomised controlled trial (RCT) of Screening and Brief Intervention (SBI) for cannabis, stimulants & opioids Participants from PHCs in Australia, Brazil, India, USA Intervention compared to waitlist control group at baseline with three month follow up All administered ASSIST and intervention participants received brief intervention for drug that scored highest

10 Total Illicit Substance Involvement Scores BI and Control at Baseline and Follow up (N=628) WHO ASSIST Phase III Technical Report, 2008: Pooled data p<0.01

11 Cannabis Specific Substance Involvement Scores BI and Control at Baseline and Follow up (N=328) WHO ASSIST Phase III Technical Report, 2008: Pooled data p<0.05

12 Stimulant Specific Substance Involvement Scores BI and Control at Baseline and Follow up (N=229) WHO ASSIST Phase III Technical Report, 2008: Pooled data p<0.005

13 Opioid Specific Substance Involvement Scores BI and Control at Baseline and Follow up (N=73) WHO ASSIST Phase III Technical Report, 2008: Pooled data p<0.07

14 Strength of Evidence about SBIRT for Illicit Drugs: Promising but limited data

15 NIDA Screening and Treatment Resources for Medical and Health Professionals

16 Online Resource Guide Reasons for alcohol, tobacco, illicit drug screening. Instructions on how to implement screening (based on WHO ASSIST). The five A s of intervention Ask, Advise, Assess, Assist, Arrange based on patient s responses. Scripts on how to discuss drug use with patients. Additional Resources.

17 Download PDF Version Introduction Before You Begin Screening and brief intervention for drug use Step 1: Ask about drug use Step 2: Screen for substance use disorders Step 3: Discuss results & conduct brief intervention Step 4: Offer continuing care at follow-up visits Appendices Support Materials Frequently Asked Questions Glossary of Terms

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19 Summary: Getting General Medicine to Address Addictions Promising Practice: Screening and Brief Intervention or Referral to Treatments (SBIRT). Improving development of medications. Blending science and services to address practice relevant research.

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21 ADDICTION IS A DISEASE OF THE BRAIN as other diseases it affects the tissue function Decreased Heart Metabolism in Heart Disease Patient High No Healthy Heart Disease Heart Diseased Heart Decreased Brain Metabolism in Drug Abuse Patient Low No Cocaine Abuse Cocaine Abuser Sources: From the laboratories of Drs. N. Volkow and H. Schelbert

22 Circuits Involved In Drug Abuse and Addiction EXECUTIVE FUNCTION/ INHIBITORY CONTROL OFC MOTIVATION/ DRIVE PFC SCC ACG NAc Amyg Hipp VP REWARD MEMORY/ LEARNING

23 Non Addicted Brain Addicted Brain Control Control CG STOP Saliency NAc Drive OFC Saliency Drive GO Memory Amygdala Memory

24 Dopamine Transporters Dopamine Dopamine Receptors

25 1. Reward Circuit NAcc VP REWARD Drugs of Abuse Engage Systems in the Motivation Pathways of the Brain

26 Drugs of Abuse Cause a Release of Dopamine frontal cortex % of Basal Release AMPHETAMINE hr Time After Amphetamine nucleus accumbens VTA/SN % of Basal Release Empty Box Feeding FOOD Time (min) Di Chiara et al.

27 Drugs of Abuse Cause a Release of Dopamine % of Basal Release Accumbens AMPHETAMINE DA DOPAC HVA hr Time After Amphetamine % of Basal Release Accumbens COCAINE DA DOPAC HVA hr Time After Cocaine % of Basal Release NICOTINE Accumbens Caudate % of Basal Release Accumbens MORPHINE Dose (mg/kg) hr Time After Nicotine hr Time After Morphine Source: Di Chiara and Imperato

28 2. Memory circuit Hipp MEMORY/ LEARNING Amyg MEMORY/ People, Place and Things

29 CRAVING INDUCTION IN PET SETTING 5 N = 13 4 CRAVING Neutral STIMULI Cocaine

30 Cocaine Craving: Population (Cocaine Users, Controls) x Film (cocaine ) Cingulate Signal Intensity (AU) Cocaine Film Ant Cing IFG Controls Cocaine Users Garavan et al A.J. Psych 2000

31 Cocaine Craving: Population (Cocaine Users, Controls) x Film (cocaine, erotic) Cingulate Signal Intensity (AU) Cocaine Film Erotic Film Ant Cing IFG Controls Cocaine Users Garavan et al A.J. Psych 2000

32 Even Unconscious Cues Can Elicit Brain Responses Brain Regions Activated by 33 millisecond Cocaine Cues (too fast for conscious recognition) Childress, et al., PLoS ONE 2008

33 Dopamine Released When Viewing Cocaine Cues Neutral video Viewing a video of cocaine scenes decreased specific binding of [11C]raclopride presumably from DA increases (N=18) Volkow et al J Neuroscience 2006

34 3. Motivation & Executive Control Circuits EXECUTIVE FUNCTION INHIBITORY CONTROL PFC ACG OFC SCC MOTIVATION/ DRIVE Dopamine is also associated with motivation and executive function via regulation of frontal activity.

35 Dopamine Measures Obtained DA D2 Receptors Anatomy DA DA DA DA DA DA DA signal Dopamine Synapse Metabolism

36 DA D2 Receptor Availability DA D2 Receptor Availability Dopamine D2 Receptors are Lower in Addiction Cocaine DA DA DA DA DA DA DA DA DA DA DA DA Meth Reward Circuits Non Drug Abuser Alcohol DA DA DA DA DA DA Heroin control addicted Reward Circuits Drug Abuser

37 Brain Glucose Metabolism in Cocaine Abusers (n=20) and Controls (n=23) 60 CG CG micromol/100g/min micromol/100g/min Controls Controls Abusers OFC Abusers P < 0.01 P < 0.005

38 Frontal Cortex Glucose Metabolism is Correlated with Dopamine D2 Receptors in Striatum Inhibitory Control CG PreF OFC Striatum Salience Attribution control cocaine abuser OFC umol/100g/min OFC umol/100gr/min r = 0.7, p < DA D2 Receptors (Ratio Index) Cocaine Abusers METH Abusers r = 0.7, p < DA D2 Receptors (Bmax/kd)

39 The fine balance in connections that normally exists between brain areas active in reward, motivation, learning and memory, and inhibitory control EXECUTIVE FUNCTION INHIBITORY CONTROL PFC OFC MOTIVATION/ DRIVE ACG SCC NAcc Amyg Becomes severely disrupted in ADDICTION Hipp VP REWARD MEMORY/ LEARNING

40 Non Addicted Brain Addicted Brain Control Control CG STOP Saliency NAc Drive OFC Saliency Drive GO Memory Amygdala Memory 40

41 Effective Strategies Attend to Multiple Aspects of Addiction: Behavior Biology Social Context

42 Treating the ADDICTED Brain REWARD CONTROL DRIVE Decrease rewarding value of drugs MEMORY

43 Outpatient Study: Percent of Negative Urines After Depot Naltrexone Administration 80% 70% 60% 50% 40% 30% 20% 10% 0% Visits (2 per week) Placebo 192 mg Dose 384 mg Dose Comer, S. D., Sullivan, M. A., Yu, E., Rothenberg, J. L., Kleber, H. D., Kampman, K. et al. Arch Gen Psychiatry, 63, ,

44 Antibodies can reduce brain concentrations Capillary Blood Flow Antibody holds drug in blood stream Brain 44

45 Cocaine free Urines Enhanced in Vaccine Responders Greater improvement, weeks (p <.001) Better Response (p <.03), weeks Martell, B. A. et al. Arch Gen Psychiatry 2009;66:

46 Medications for Relapse Prevention Control CG Interfere with drug s reinforcing effects Executive function/ Inhibitory control Vaccines DA D3 antagonists Biofeedback Modafinil Saliency NAc Drive OFC Strengthen prefrontal striatal communication Interfere with conditioned memories (craving) Adenosine A2 antagonists DA D3 antagonists Antiepileptic GVG N acetylcysteine Memory Amygdala Adapted from: Volkow et al., J Clin Invest 111(10): , 1451, 2003 Teach new memories Counteract stress responses that lead to relapse Cycloserine CRF antagonists

47 Summary: Getting General Medicine to Address Addictions Promising Practice: Screening and Brief Intervention or Referral to Treatments (SBIRT). Improving development of medications. Blending science and services to address practice relevant research.

48 Outcomes can be improved by: Developing interventions that are highly effective as delivered, or Implementing an effective intervention more widely.

49 Information Dissemination 49

50 Information Dissemination Essential first step, BUT. Generally produces only a vague awareness that new science exists Does not address the conditions and circumstances of the numerous providers, clients and contexts involved.

51 Community Bedside RESEARCH BLENDING and PRACTICE Bench Working in real world settings is key.

52 National Drug Abuse Treatment Clinical Trials Network (CTN) Criminal Justice Drug Abuse Treatment Studies (CJ DATS) Research Centers Coordinating Center

53 Addressing Drugs and Crime Public Health Approach disease treatment Public Safety Approach illegal behavior punish High Attrition High Recidivism

54 Successful Reentry Programs Use an Integrated Public Health Public Safety Strategy Communitybased treatment Blends functions of criminal justice and treatment systems to optimize outcomes Close supervision Opportunity to avoid incarceration or criminal record Consequences for noncompliance are certain and immediate

55 Medications are an important part of treatment. Methadone Experiment: 6 Mo Post Release (N=201) signif. diff from referral signif. diff from treatment only on release Source: Gordon, M.S., Kinlock, T.W., Schwartz, R.P., O Grady, K.E. (2008), Addiction.

56 Few Inmates Fill Antiretroviral Therapy (ART) Prescriptions after Prison Release Percent % 17.7% 30% Had prescription filled within: 0 10 days 30 days 60 days Baillargeon et al., JAMA 2009;301:

57 Plasma HIV May Matter for Prevention: Community Incidence Parallel to Plasma HIV Level Evans, et al., BMJ 2009; 338: b1649

58 In Treating Addiction We Need to Keep Our Eye on the Real Target Abstinence Abstinence Abstinence Functionality Functionality Functionality in in in Family, Family, Family, Work Work Work and and and Community Community Community

59 We Need to Treat the Whole Person!

60 Finally, We Need to View and Treat Addiction As A Chronic, Relapsing Illness

61 Drug Addiction as a Chronic Disease: Relapse Rates Similar to Other Chronic Medical Conditions 100 Percent of Patients Who Relapse to 60% 30 to 50% 50 to 70% 50 to 70% 0 Drug Dependence Type I Diabetes Hypertension Asthma Source: McLellan, A.T. et al., JAMA, Vol 284(13), October 4, 2000.

62 Addiction is Chronic but NOT Permanent: Yr 8 Abstinence by Yr 7 Abstinence Length Dennis ML, Foss MA, Scott CK. Eval Rev 2007;31:

63 Outcome In Hypertension AT McLellan, Treatment Research Institute

64 Outcome In Diabetes AT McLellan, Treatment Research Institute

65 Outcome In Addiction AT McLellan, Treatment Research Institute

66 If we treat a diabetic and symptoms don t subside.what do we do? Would we increase the dose? Would we change medications? Would we change treatment approaches? Would we fail to provide ongoing treatment for a diabetic? AT McLellan, Treatment Research Institute

67 Treatment Can be Successful: Program Results on 802 Addicted Physicians Long term follow up (average 56 mos. on average) 78% started with residential care 100% outpatient care (about 6 9 mos.) 19% tested positive for drugs (once+) 73% were licensed and practicing medicine 5 years after program entry Source: AT McLellan et al., British Medical Journal (2008), BMJ 2008;337:a2038

68 Summary Drug Addiction is a neuropsychiatric (i.e. brain) disease that involves multiple brain systems including those involved in: Reward/reinforcement, memory, executive control and motivation/drive. has roots in childhood and adolescence.

69 Summary Drug Addiction has a better outcome if treated. Offering medications should be considered. Effective treatment generally requires more than education, abstinence, and self help.

70 Summary Drug Addiction is often chronic, requiring sustained treatment. Relapse is commonly part of recovery. Consistent, coordinated responses are key.

71 Summary Addiction is a Brain Disease with developmental roots. Drug treatment can be effective. Addiction should be viewed from a long term/chronic perspective.

72 Summary: Potential Areas for Development and Collaboration Screening, brief interventions or referral to treatment (SBIRT). Training and outreach to clinicians. Development of medications. Epidemiological monitoring.

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