A Real Case. Substance Use Disorders in Primary Care: Screening, Brief Interventions, Pharmacotherapy. Quiz Your Clinic Panel

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1 Substance Use Disorders in Primary Care: Screening, Brief Interventions, Pharmacotherapy Katherine Julian, M.D. UCSF Division of General Internal Medicine August 7, 2013 A Real Case 31 yo man presenting to resident clinic for new patient appt Recently hospitalized with new onset atrial fibrillation. Resolved with cardioversion. Given coumadin and presenting to titrate this medication. Prompted to take an alcohol history binge drinking with indications of alcohol dependence Quiz Your Clinic Panel In your clinic panel, what percentage of your current clinic patients would be classified with alcohol abuse or dependence*? Substance Use Issues are Highly Prevalent in Americans At Risk Drinking* 23% Illicit Drug Use 8% A. <1% Substance Abuse/Dependence 9% B. 2-5% C. 6-9% D. 10% 14% 24% 35% 27% Alcohol 7% Illicit Drugs 3% E. 20% < 1 % 0% 2-5 % 6-9 % 1 0 % 2 0 % SAMHSA, National Survey on Drug Use and Health, 2008 Ages 12+ in the United States 1

2 Alcohol Use in Primary Care 3439 primary care patients 11% had at risk drinking defined as any of the following: > 2 drinks/day > 2 episodes of 5+ drinks/day in 30 days Drinking and driving Curry SJ, et al. Prev Med 2000;31(5): Alcohol Use Disorders in Older Adults 3% met full criteria for an alcohol use disorder At-risk drinking was reported in: 17% of men, 11% of women ages % of all respondents ages % of all respondents ages 65+ Binge drinking was reported in: 20% of men, 6% of women ages % of all respondents ages % of all respondents ages 65+ NSDUH, 2009 Blazer D, Wu L. Am J Psychiatry, 2009 Outline Substance Use Disorders - Definitions SBIRT Screening: quickly assess use and severity of alcohol, illicit drugs, and prescription drug abuse Brief Intervention: a 3-5 minute motivational intervention given to risky or problematic substance users Referral to Treatment Motivational Interviewing ETOH and Opiate Substance Use Pharmacotherapy Why SBIRT? The Evidence Brief interventions can reduce alcohol use for at least 12 months in patients who are not alcohol dependent % of patients can be expected to change their drinking behaviors as a result of a brief intervention. Babor & Higgins-Biddle, 2000; Fleming and Manwell,

3 Quiz Which of the following is NOT considered to be at risk drinking? A. 45 yo woman who drinks 1-2 glasses of wine each night B. 70 yo man who drinks 1-2 beers each night C. 25 yo woman who drinks 4-5 drinks once a week when she goes out with friends D. 40 yo man who drinks 1-2 glasses of wine each night 4 5 y o w o m a n w h... 8% 7 0 y o m a n w h o... 17% 2 5 y o w o m a n w h... 11% 4 0 y o m a n w h o... 64% Men Definition At Risk Drinking >4 drinks/day or >14 drinks/week Women (and > than 65 yrs) >3 drinks/day or >7 drinks/week Increased risk of alcohol-related problems Quiz Which of the following is NOT considered to be at risk drinking? A. 45 yo woman who drinks 1-2 glasses of wine each night B. 70 yo man who drinks 1-2 beers each night C. 25 yo woman who drinks 4-5 drinks once a week when she goes out with friends D. 40 yo man who drinks 1-2 glasses of wine each night A standard drink is any drink that contains about 14 grams of pure alcohol (about 0.6 fluid ounces or 1.2 tablespoons) What is a Drink? 3

4 New DSM5 - Substance Use Disorder No longer need to differentiate between substance abuse and substance dependence Each substance can be categorized as a disorder Ex: Alcohol use disorder, stimulant use disorder, etc Grade Severity: Mild, Moderate, Severe New DSM5 - Substance Use Disorder Maladaptive pattern of substance use leading to clinically significant impairment or distress, as manifested by 2 (or more) of the following, occurring within a 12-month period: Failure to fulfill role obligations Recurrent substance use in situations that are physically hazardous Persistent use despite social/interpersonal problems Criteria for Substance Use Disorder (contd) Tolerance Withdrawal Using more than originally intended Persistent desire or unsuccessful efforts to cut-down Time spent obtaining/using substance or recovering from side effects Reduction of social/occupational activities Use despite physical/psychological problems Craving Need 2 criteria for SUD 2-3 criteria =mild 4-5 = moderate >6 = severe Screening Some key opportunities include: As part of a routine examination Before prescribing a medication that interacts with alcohol or other drugs In the emergency department or urgent care center When seeing patients who.. Are pregnant or trying to conceive Have health problems that might be alcohol or drug induced/ related Have a chronic illness not responding to treatment Are likely to drink heavily NIAAA, Helping Patients Who Drink Too Much: A Clinician s Guide (Updated) 4

5 How to Screen? Ask permission: Would it be ok to spend the next few minutes talking about alcohol? Pre-screen: Do you sometimes drink beer, wine, or other alcoholic beverages? Single Alcohol Screen Question: Men: How many times in the past year have you had 5 or more drinks in one day? Women (or >65 yo): How many times in the past year have you had 4 or more drinks in one day? Positive Screen=1 or more How to Screen? Single Drug Use Screen Question: How many times in the past year have you used an illegal drug or used a prescription medication for nonmedical reasons? Positive Screen=1 or more Smith PC, et al. J Gen Intern Med 2009;24(7); NIAAA Guidelines 2005 Smith PC, et al. J Gen Intern Med 2009;24(7); NIAAA Guidelines 2005 Evidence for the Single Screen Single Question Screen Sensitivity/specificity: 88%/ 67% for alcohol use d/o Sensitivity/specificity: 82%/79% for unhealthy use CAGE: Sensitivity/specificity: 92%/ 48% for alcohol dependence AUDIT Sensitivity/specificity: 96%/ 57% for unhealthy use Sensitivity/specificity: 90%/ 61% for alcohol use d/o Single Drug Screen Sensitivity/ specificity: 100%/ 74% for drug disorder Sensitivity/specificity: 71%/ 95% for use with consequences Smith PC, JGIM 2009; Smith PC, Arch Intern Med 2010 A Positive Screen 1 or more heavy drinking days Any positive drug screen What to do next? Assess Determine how many drinks/day in a week Ask which drugs the patient has been using Ask about negative impacts The follow-up questions are to assess impact and whether or not use is serious enough to warrant a substance use disorder diagnosis. 5

6 Criteria for Substance Use Disorder Failure to fulfill role obligations Recurrent substance use in situations that are physically hazardous Persistent use despite social/interpersonal problems Tolerance Withdrawal Using more than originally intended Persistent desire or unsuccessful efforts to cut-down Time spent obtaining/using substance or recovering from side effects Reduction of social/occupational activities Use despite physical/psychological problems Craving Determining At Risk vs. Substance Use Disorder Pts who meet criteria for at-risk should get a brief intervention Patients who meet substance use disorder criteria abuse should get a Brief intervention AND A referral to specialty care (if they are willing) AND Be considered for pharmacotherapy What is a Brief Intervention? Advise and Assist the patient Short, 3-5 minute motivational interviews that encourage patients to create a plan of action (ex: reduce drinking) that is based on their willingness to change their behavior Feedback and recommendations are given respectfully in the form of useful information. Brief Intervention Non-judgmental but give direct, honest feedback Provide advice on what a patient should do Negotiate a concrete, realistic plan for behavioral change If not ready to change harm reduction Plan for follow-up 6

7 HOW TO HELP PATIENTS: A CLINICAL APPROACH: NIAAA 2005 Resource for Clinicians HOW TO HELP PATIENTS: A CLINICAL APPROACH AT-RISK DRINKING AT-RISK DRINKING Advise and Assist State your conclusion and recommendation clearly Advise and Assist State your conclusion and recommendation clearly image credit: Comstock You are drinking more than is medically safe. image credit: Comstock I strongly recommend that you cut down (or quit) and I m willing to help. HOW TO HELP PATIENTS: A CLINICAL APPROACH HOW TO HELP PATIENTS: A CLINICAL APPROACH AT-RISK DRINKING Advise and Assist State your conclusion and recommendation clearly Gauge readiness to change drinking habits image credit: Comstock Are you willing to consider making changes in your drinking? AT-RISK DRINKING Advise and Assist Is the patient ready to commit to change at this time? NO Do not be discouraged. Ambivalence is common. Your advice has likely prompted a change in your patient s thinking. With continued reinforcement, your patient may decide to take action. For now, restate your concern about his or her health. 7

8 HOW TO HELP PATIENTS: A CLINICAL APPROACH HOW TO HELP PATIENTS: A CLINICAL APPROACH AT-RISK DRINKING AT-RISK DRINKING Advise and Assist Is the patient ready to commit to change at this time? NO Encourage reflection: Ask patients to weigh what they like about drinking versus their reasons for cutting down. What are the major barriers to change? Reaffirm your willingness to help when he or she is ready. Don t forget FOLLOW-UP Advise and Assist Is the patient ready to commit to change at this time? YES Help set a goal to cut down to within maximum limits or abstain for a period of time. Agree on a plan, including -What specific steps the patient will take -How drinking will be tracked -Who can help -How to manage high-risk situations HOW TO HELP PATIENTS: A CLINICAL APPROACH HOW TO HELP PATIENTS: A CLINICAL APPROACH Example 2 -- For patients who meet the criteria for ALCOHOL USE DISORDERS Advise and Assist State your conclusion and recommendation clearly. Relate to the patient s concerns and medical findings, if present. I believe that you have an alcohol use disorder. You are drinking more than is medically safe. I m concerned about your health. I strongly recommend that you quit drinking and I m willing to help. image credit: Comstock ALCOHOL USE DISORDERS Advise and Assist Negotiate a drinking goal: Abstaining is the safest course for most patients with AUDs. Patients who have milder forms of alcohol abuse or dependence and are unwilling to abstain may be successful at cutting down. If needed, refer for additional evaluation by Specialized Substance Abuse Services Consider recommending a mutual help (self-help) group, like AA. For patients with dependence, consider medically managed withdrawal vs. medications 8

9 Motivational Interviewing Motivational Interviewing Specialized skill set designed to help patients become ready and motivated to change health-related behaviors Stages of Change from Transtheoretical Model Mentality of the Stages Maintenance Lapse Action Contemplation Precontemplation Preparation 9

10 Motivational Interviewing Principles Express empathy Develop discrepancy Roll with resistance patients aren t resistant (they just aren t seeing things the way you do!) Support self-efficacy MI: Assess Readiness to Change Readiness Ruler On a scale of 0-10, how ready are you to stop drinking? I would say about a 3 So it sounds like you aren t too interested right now. But I m curious why you said 3 rather than 0. OR What would it take to move you to a 5? Well, I know I should stop at some point. Can you say a bit more about why you think that you should stop? MI: Enhance Motivation Listen for change talk Small verbal cues that the patient has thought about changing/need to change or health consequences of their behavior I was worried there at first, but I don t really think I have a problem. I don t see why everyone is making such a fuss about this. I can handle it. MI: Enhance Motivation When you hear change talk, use MI skills (OARS) to respond Open-ended questions Why do you think everyone is making such a fuss? Affirmations I can see you really care a lot about your health Reflections You are really considering whether you should cut down Summary statements: tie together multiple points I hear you saying that you don t drink more than most people but everyone is making a fuss about your drinking 10

11 MI Ask Importance/Confidence Questions On a scale of 1-10, how important is it to you to stop drinking (or cut back)? On a scale of 1-10, how confident are you that you can stop drinking (or cut back)? This will help guide your next steps Ask about pros/cons of the behavior MI: Negotiating a Plan Plan should match the patient s level of readiness to change It is concrete, specific and realistic Patient agrees to it and is able to repeat it back to you MI Practice Continuum of Care for Substance Use Disorders Self-help (AA, etc) Outpatient with or without sober housing Intensive outpatient - > 3x/wk Day treatment Usually group-based Sober Housing ( Halfway House --can be unstaffed) Residential - brief (< 28 da) or extended, non-medical ( rehab ) Inpatient hospital for true medical detoxification Aftercare usually low intensity 1/wk indiv or group 11

12 Pharmacotherapy Addiction Treatment Model: Treating Limbic Drive and Cortical Thinking Structures Decision Making (Counseling) From Pettinati, NIH 2006 Limbic Drive (Pharmacotherapy) Substances for which Pharmacotherapy is Available Opioids Alcohol Tobacco (nicotine dependence) Substances for which Pharmacotherapy is Not Available Cocaine Methamphetamine Hallucinogens Cannabis Solvents/Inhalants Phases of Substance Use as Targets for Pharmacotherapy Intoxication/overdose Withdrawal/detoxification Abstinence initiation/use reduction Relapse prevention Sequelae (psychosis, agitation, etc.) 12

13 Alcohol Use Disorder Pharmacotherapy Two Phases of Alcohol Use Disoder Treatment: Acute Alcohol Withdrawal Subacute/Chronic Treatment: Maintenance medications to reduce use or prevent relapse to alcohol use (FDA approved) Disulfiram Acamprosate Naltrexone (oral and injectable) Minimum trial of 3 months (risk of relapse high 6-12 months) Alcohol Withdrawal Most alcohol withdrawal is managed in an inpatient setting Meds typically include: Benzodiazepines Anticonvulsants Adjunctive Medications/supplements Avoid outpatient detox; best to refer to specialized programs with close monitoring What s the role of an outpatient provider? Refer for alcohol detox and ongoing substance abuse treatment Alcohol Relapse Prevention Meds: Disulfiram (Antabuse) Blocks alcohol metabolism (prevents acetaldehyde acetate); increase in blood acetaldehyde levels Antabuse reaction: flushing, weakness, nausea, tachycardia, hypotension (up to 2 weeks later!) VA Cooperative Study of Disulfuram in 605 men No effect on number of patients maintained abstinence Among non-abstinent, signif fewer drinking days High rate of non-compliance: 80% If adherent, more likely to be abstinent Works better if given in monitored fashion Alcohol Relapse Prevention Meds: Disulfiram (Antabuse) Pt should avoid alcohol containing foods Clinical Dose: 250mg daily (range mg/d) SE: metallic taste, sulfur-like odor Rare: hepatotoxicity, neuropathy, psychosis Check LFTs before, q1mo X 3, then q3 mo Contraindications: CAD, hypersen to rubber, varices, renal disease, severe hepatic dysfunction (LFTs> 3x upper level of nl) Encourage patient to attend substance abuse treatment where disulfiram could be administered by staff/family Fuller RK, et al. JAMA, 1986;256 13

14 Alcohol Relapse Prevention Meds: Acamprosate Acts on GABA and glutamate neurotransmitter systems Impact is anti-craving, reduced protracted withdrawal Dose: 2 g daily (6 pills/day= TWO 333 mg pills three times/d) SE: Diarrhea (up to 16%), nausea, itching (up to 4%) Contraindications: severe renal disease (creat cl < 30 ml/min); dose adjust if CrCl Only approved for people who are abstinent Alcohol Relapse Prevention Meds: Acamprosate Recommended length of treatment: 1 year Effective in reducing relapse to alcohol use in studies leading to FDA approval Meta-analysis of European trials: 36% on acamprosate abstinent at 6 months vs. 23% on placebo Not effective in Project COMBINE: 1383 patients Only naltrexone signif increased % days abstinent and time to heavy drinking More severe dependence in European trials (acamprosate with greater effect in longer h/o dependence)? Fewer abstinence days required to enter COMBINE Mann K et al. Alcohol Clin Exp Res, 2004 Anton RF et al. JAMA, 2006 Naltrexone for Alcohol Use Disorder Similar structure to naloxone (Narcan) Potent inhibitor of Mu opioid receptor binding May explain reduction of relapse Endogenous opioids involved in the reinforcing (pleasure) effects of alcohol May explain reduced craving for alcohol Endogenous opioids may be involved in craving alcohol Shown to reduce drinking in those who have cut down but not abstained (28% naltrexone vs. 43% placebo) Naltrexone for Alcohol Use Disorder Cochrane Review of NTX (based on 50 RCT) Reduced risk of heavy drinking to 83% of the risk vs. placebo (RR 0.83; CI ) Decreased drinking days by 4% Not significant for return to any drinking (RR 0.96; CI ) Estimate helps 1 out of 9 Littleton & Zieglgansberger, (2003) Am J Addict 12[Suppl1]:S3-S11 Srisurapanont & Jarusuraisin (2005) Cochrane Database Syst Rev Jan 25;(1):CD

15 Pharmacotherapy of Alcohol Dependence: Naltrexone Oral Naltrexone Hydrochloride DOSE: 50 mg per day Extended-Release Injectable Naltrexone (Vivitrol) 380mg IM per month 624 patients 25% decrease in heavy drinking days vs. placebo More effective if >7 days abstinence Too little data to make conclusion if as effective as PO form (Cochrane review 2010) Must be opioid-free for 7-10 days before starting Naltrexone Safety Can cause hepatocellular injury in very high doses (eg 5-10 times higher than normal) Contraindicated in acute hepatitis or liver failure Check liver function before, q1 month for 3 months, then q 3 months Caution about NSAIDS May have additive hepatic effects Garbutt et al. JAMA, 2005 Naltrexone Safety Other contraindications Concomitant opioid analgesics Opioid dependence or withdrawal Medical conditions requiring opioid analgesics Pregnancy (Category C) Main adverse effects: Gastrointestinal: ab pain, N/V Headache Dizziness Summary Alcohol Use Disorder If abstinent: Consider disulfiram as insurance (if monitored) Consider naltrexone for relapse prevention Can consider acamprosate If still drinking Consider naltrexone If on opioids Consider acamprosate 15

16 Case Study A 42 year old man with a 14 year history of alcohol dependence relapsed to alcohol abuse 3 months ago. He currently reports drinking 3-5 drinks 4-5 times/wk, but states that he when he abstains for a day or two occasionally he does not experience alcohol withdrawal symptoms. However, his spouse is upset with his drinking and he now wants medication to help him to abstain. He tried naltrexone in the past, but says it didn t help much. He takes no other medications and has no known allergies. What of the following would you recommend? A. Liver function tests B. Acamprosate 666 mg three times daily C. Disulfiram 250 mg/d (from E. McCance-Katz, 2010) L i v e r f u n c t i o n % A c a m p r o s a t e % 0% D i s u l f i r a m Case Study: Answer A and C: This patient has a long and difficult history of alcohol dependence. He has failed naltrexone in the past and acamprosate is not likely to be helpful (the Combine Study showed it to be inferior to naltrexone). He has significant consequences of his drinking; is motivated to quit; If his liver functions indicate that he does not have significant impairment; a trial of disulfiram 250 mg daily might help. (from E. McCance-Katz, 2010) Quiz Which of the following is the most commonly misused class of prescription drugs? A. Opiates B. Stimulants C. Benzodiazepines 73% 3% 25% Rates of Prescription Narcotic Abuse Prescription Narcotic Abuse Prevalence: 12 th graders: 1992: 3.3% 2007: 9.2% 179% increase over 15 years OxyContin Vicodin 8 th 1.8% 8 th 2.7% 10 th 3.9% 10 th 7.2% 12 th 5.2% 12 th 9.6% O p i a t e s S t i m u l a n t s B e n z o d i a z e p i n e... Source: Monitoring the Future,

17 Source Where Pain Relievers Were Obtained for Most Recent Nonmedical Use among Past Year Users Aged 12 or Older: 2006 Pharmacotherapies for Opiate Dependence Source Where Respondent Obtained More than One Doctor 1.6% One Doctor 19.1% Drug Dealer/ Stranger 3.9% Bought/Took from Friend/Relative 14.8% Bought on Internet 0.1% Other 1 4.9% Free from Friend/Relative 55.7% Source Where Friend/Relative Obtained One Doctor 80.7% More than One Doctor 3.3% Free from Friend/Relative 7.3% Bought/Took from Friend/Relative 4.9% Drug Dealer/ Stranger Other 1 1.6% 2.2% Methadone Buprenorphine Naltrexone Opioid Dependence Maintenance Therapy: Methadone Can only be prescribed through a registered narcotic treatment program Characteristics Long acting mu agonist Duration of action: h mg will block withdrawal, but not craving Illicit opiate use decreases with increasing methadone dose mg is more effective at reducing opioid use than lower doses (e.g.: mg/d) Strain EC, et al. JAMA, 1999 Opioid Dependence Therapy: Methadone Agonist therapy Prevention of Withdrawal Syndrome Induction of Tolerance Who is appropriate for methadone therapy? > 18 years Greater than 1 year of opioid dependence Medical compromise Infectious disease Pregnancy* ECG: methadone prolongs QT in approx 2% (CSAT 2005) 17

18 Opioid Dependence Maintenance Therapy: Methadone Can interact with many commonly used medications Decreased methadone concentrations: Pentazocine Phenytoin Carbamazepine Rifampin Many HIV meds Increased methadone concentrations: Ciprofloxacin Fluvoxamine Discontinuation of inducing drug McCance-Katz et al Opioid Dependence Maintenance Therapy: Buprenorphine Mu Opioid receptor, high affinity, partial agonist Binds opioid receptors; slow to dissociate If recent opioids, may withdraw OD can t be reversed with standard dosing of naloxone Dosing may be daily, every other day or three times weekly Average dose 8-16 mg daily Little effect on respiration or cardiovascular responses at high doses McNicholas, 2004 Opioid Dependence Maintenance Therapy: Buprenorphine To reduce diversion, combined with naloxone in 4:1 ratio Cheaper price than buprenorphine alone! Occas increase in LFTs SE: N/V (?if due to withdrawal) Equivalent to lower dose of methadone in reducing illicit opioid use (though 80mg methadone better) Primary care physicians may be providers of this treatment as well as addiction specialists Opioid Dependence Maintenance Therapy: Buprenorphine Metabolized by cytochrome P450 Drug Interactions: Atazanavir/ritonavir: increases buprenorphine concentrations; rifampin: decreases buprenorphine concentrations; opiate withdrawal possible Buprenorphine DEA certification required to prescribe (8 hrs of training) Can treat up to 100 patients 18

19 Opioid Dependence Therapy: Antagonist Treatment (Naltrexone) Prevent impulsive use of drug Relapse rates high (90%) following detoxification with no medication treatment Dose (oral): 50 mg daily, 100 mg every 2 days, 150 mg every third day Side effects: hepatotoxicity, monitor liver function tests every 3 months Biggest issue is lack of compliance Injectable naltrexone not currently approved for opioid dependence, but likely to also be effective Take Home Points Ask, Assist, Advise, Refer: At-risk and substance use disorders common Three medications FDA-approved for the maintenance treatment of alcoholism Disulfiram: for those already abstaining Naltrexone (oral daily or injectable once monthly): To reduce use in those still drinking Acamprosate: for those who can t take Naltrexone Take Home Points Three medications FDA-approved for treatment of opioid dependence Methadone (must be given through a licensed narcotic treatment program) Buprenorphine/naloxone (Suboxone) available by prescription from qualified providers) Naltrexone: an opioid antagonist best for highly motivated patients Resources Thank You! Local mutual help groups (resources) Substance Abuse Facility Treatment Locator Website