This document provides an overview of addiction psychiatry including: - The neurobiology of addiction and how chronic drug use decreases dopamine levels and impacts brain regions responsible for motivation, inhibition and determining importance. - Dually diagnosed patients often have substance use disorders and psychiatric illnesses which complicate treatment. Integrated treatment is recommended. - Motivational interviewing and relapse prevention therapy aim to help patients through the stages of change to maintain sobriety. - Pharmacological interventions for various addictions including opioids, alcohol and cocaine are discussed though more research is still needed on effective medications. - A case example involves assessing potential prescription opioid misuse or addiction in a chronic pain patient.

1. Addiction Psychiatry Jake Kagan MDBarre Family Health Center September 21, 2009

2. Outline Definition of addiction Overview of the neurobiology of addiction Dually diagnosed patients; diagnosis and management Motivational Interviewing Relapse Prevention Psychopharm interventions for addiction Case 1

3. DSM-IV criteria for Dependence Although including physiological signs, addiction is largely BEHAVIORAL >3 of the following… Tolerance Withdrawal Using more than intended Unsuccessful attempts to cut down Time spent is excessive Activities are neglected Continued use despite problems developing 2

4. Indications that patients are misusing/abusing prescriptions Early refills, lost Rx, escalating amounts requested, “doctor shopping” – although these can be indications of undertreated pain! Tox screens positive for other substances Patients appear intoxicated in the office  What to do… Get collateral: family, pharmacy, other providers, prior providers Get a consult, slow down the pace 3

5. Neurobiology… What happens to the brain when drugs are introduced and what happens over time? Why do people continue to use despite decreasing experience of being high and mounting social/physical problems? How can we use this knowledge to HELP people get sober and maintain – not pathologize 4

6. Dopamine pathways DA neuron cell bodies lie in the VTA (midbrain=meso) Mesolimbic From midbrain to nucleus accumbens; also amygdala and hippocampus Mesocortical From midbrain to the prefrontal cortex, orbitofrontalcortex and anterior cingulategyrus 5

7. Role of Dopamine: Acute drug administration Psychoactive substances may 1) increase DA release, 2) inhibit reuptake, 3) act as DA agonist Acute increases in DA in both the mesolimbic and mesocortical pathways are thought to be essential to the initial “liking” and reinforcement of drug taking (The Reward Pathway) Specifically – Nucleus accumbens is essential to reinforcement, amygdala and hippocampus to cue related learning (setting up cravings) Drugs produce supraphysiological DA release – HIJACKING the normal pathways or what’s important 6

8. Taking drugs Good feeling (Reward Pathway) Hedonistic Theory  we keep using b/c it felt good (positive reinforcement) But… Why keep using when the good feeling is gone? (prevent w/d, negative reinforcement) When one’s life has been destroyed? Why relapse after years of sobriety? 7

9. Role of Dopamine: Chronic Administration  GLOBAL DECREASE IN DA (hypodopinergic) So what??? Orbital Frontal Cortex: Salience Attribution (Nora Volkow) – responsible for telling us what is important, food/sleep, not drugs! CingulateGyrus: responsible for INHIBITION Dorsolateral Prefrontal Cortex: responsible for MOTIVATION 8

10. With chronic administration… The brain becomes less sensitive to cues that really matter (food), more sensitive to cues involving drugs (including smells, sounds, etc), while simultaneously losing its inherent ability to INHIBIT behavior. We have lose the ability to identify what’s important while becoming markedly more impulsive. 9

11. As if that weren’t bad enough… Corticotropin Releasing Factor (CRF) and the HPA axis (stress response) In response to drug use, and more precisely, activation of the mesolimbic DA system, CRF and the HPA axis are upregulated In acute withdrawal this leads to physiological and psychological withdrawal However, increases in cortisol, CRF, NE in addition to neuropeptide Y, nociceptin, vasopressin are thought to persist weeks/months into sobriety leading to anxiety, dysphoria that we call protracted withdrawal 10

12. Dually diagnosed patients (addiction + psychiatric illness) Prevalence (NCS and NCS-R data) Individuals with psychiatric illness are 2.7 times more likely to have alcohol or substance use disorders (life time prevalence of 29% vs. 19.6%) Lifetime rates of addictive disorders among patients diagnosed with: Schizophrenia: 47% All affective disorders: 32% Bipolar disorder: 56.1% Social anxiety disorder: 22% for alcohol alone ADHD: 12-month prevalence is 15% vs 5% in non-ADHD responders Among those with SUDs, 53% meet criteria for psychiatric illness, 37% among those with EtOHdisorers (Compared to 32% in general population). 11

13. Dual Dx: Clinical Significance SUDs complicate/worsen comorbid psychiatric illness For example… bipolar substance abusers have earlier onset, more hospitalizations, higher rates of rapid cycling/mixed episodes, poorer txresponse In the other direction, psychiatric illness complicates/worsens the course and treatment of SUDs Substance abuse is a well known risk factor for suicide and self-injurious behavior Dual diagnoses increase the risk for violent behavior – often much greater than an additive effect Dual diagnosis pts have higher prevalence of medical comorbidities than either group independently Dually diagnosed pts have higher relapse rates than those w/”straight” addiction 12

14. Dual diagnosis – what to do? Challenges… making the psychiatric diagnosis Psychiatric sxs can be confused with intoxication/withdrawal sxs, including protracted withdrawal Patients who are using or in new sobriety are poor historians Historical approach: Clinicians would wait months/years into sobriety to make the diagnosis and treatment was NOT integrated Given that pts often self-medicate, many would relapse long before a dx was made or treatment started! Current approach: Integrated treatment Decreased threshold for making the psychiatric diagnosis Get a good hx, and collateral! Balance risks of treatment vs risks of not treating (ie are you starting an SSRI or a mood stabilizer?) 13

15. Stages of Change (Prochaska & DiClemente) Precontemplation (Not yet acknowledging that there is a problem behavior that needs to be changed) Contemplation (Acknowledging that there is a problem but not yet ready or sure of wanting to make a change) Preparation/Determination (Getting ready to change) Action (Changing behavior) Maintenance (Maintaining the behavior change) Relapse (Returning to older behaviors and abandoning the new changes) 14

17. Steps can and usually are repeated

18. Relapse is nearly always part of recovery

20. MET: Stage relevant interventions 17

21. Relapse Prevention Therapy (RPT) “Cognitive and behavioral self-efficacy program designed to teach individuals who are trying to maintain changes in their behavior how to anticipate and cope with the problem of relapse.” (Parks & Marlatt) 1) Identify high risk situations/triggers negative emotional states, interpersonal conflict, and social pressure. 2) Teach practical coping skills and cognitive strategies to avoid and manage high risk situations 3) Encourage return to treatment following relapse (relapse leads to guilt which individuals then try to medicate away) 4) Sense of self-efficacy develops with increasing time sober 18

22. Pharmacology Strength of binding (pKa) Determines if an agent can be a blocker Action at binding site (agonist, partial agonist, antagonist) Relates to how a medication “feels” but also safety, “abusability”, treating cravings Time to onset and duration of action The faster the onset, the more a substance can produce euphoria (PO, IN, smoked, IV) 19

23. Pharmacology - Opioids Buprenorphine/naloxone Partial opioid agonist, binds tightly but has ceiling effect Safe and minimal abuse potential, treats cravings and protracted withdrawal Naltrexone Full opioid antagonist (po form of naloxone) Little risk (some hepatic involvement), blocks opioids, but does not tx cravings or protracted withdrawal Methadone Full opioid agonist Administered in a clinic per DEA regulations 20

24. Pharmacology – Alcohol1 Naltrexone Mu-opioid antagonist, attenuates effect of beta-endorphin release, particularly in Nac Good initial efficacy, unclear if long term impact on abstinence and overall small effect size Studies show compliance is significant factor May have more benefit for pts with +FHx, heavy drinkers Some studies show more effective than acamprosate Depot formulations may be more effective (increased compliance) 50mg daily, risk of hepatic dysfxn 21 1 Johnson BA. Update on Neuropharmacological treatments for alcoholism: Scentific basis and clinical findings. 2008. BiochemPharmacol. 75(1):34-56

25. Pharmacology – Alcohol Acamprosate Antagonizes NMDA glutamate receptors Suppresses EtOH induced glut receptor hypersensitivity and cue related cravings Positive European studies led to FDA approval, but US studies have not shown efficacy (COMBINE study) Well tolerated (better than naltrexone) Disulfiram Inhibits aldehydedehydrogenase, resulting in build up of acetaldehyde  flushing, nausea, vomiting, palpitation SEs include hepatitis, psychosis, depression, confusional states As mechanism is purely adversive, it does nothing for cravings and pts actually have to take it! 22

26. Pharmacology - Alcohol Topiramate Not FDA approved Multiple mechanisms of action – glutamate antagonist/facilitates GABA 3 RCTs with moderate effect size including recent multisite study showing improvement in self reported drinking outcomes, GGT, some QOL measures Titrate slowly to 200mg; to be cautious as slow as 25mg/week, starting at 25mg qhs (minimizes cognitive dulling, “Dopamax” effect) 23

27. Pharmacology Cocaine Nothing is FDA approved Psychological interventions are the mainstay of treatment (contingency management) Potential medications include modafinil, naltrexone, disulfiram, GABA-ergic agents, N-acetylcysteine 24

28. Case 48 y/o man with a h/o low back pain since an MVA 10 years ago presents for a new pt appointment seeking opioids. You initially prescribe oxycodone, but 6 months later begin to wonder if you are managing addiction vs pain. What could give you more data, and what might be indicators of prescription misuse/addiction? What do we know about how pts with SUDs experience pain? What can be helpful? Get a consult, talk to peers, make treatment as structured as possible, slow down the pace. How might you approach the issue of misuse/addiction with this patient? What options for treatment would you consider? 25