Recognizing and Managing Substance Use Disorders. Disclosures

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1 Recognizing and Managing Substance Use Disorders Katherine Julian, M.D. Professor of Medicine UCSF Division of General Internal Medicine December 10, 2015 n None Disclosures 1

2 Quiz Your Clinic Panel n In your clinic panel, what percentage of your current clinic patients would be classified as atrisk drinkers? A. <1% B. 2-5% C. 6-9% D. 10% E. >20% Substance Use Issues are Highly Prevalent in Americans (12+years) At Risk Drinking* 27-29% Alcohol Dependence 3.5% Alcohol Dependence among binge drinkers 10.2% National Survey on Drug Use and Health, Prev Chronic Disease,

3 Alcohol Use Disorders in Older Adults n 3% met full criteria for an alcohol use disorder n At-risk drinking was reported in: n 13% of all respondents ages 65+ n Binge drinking was reported in: n 15% of all respondents ages 65+ NSDUH, 2009 Blazer D, Wu L. Am J Psychiatry, 2009 Outline Substance Use Disorders - Definitions SBIRT Screening Brief Intervention Referral to Treatment ETOH Substance Use Pharmacotherapy Treatment of Non-Cancer Pain: Balance risks/benefits Opiate Substance Use Pharmacotherapy 3

4 Quiz n 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 Definition At Risk Drinking n Men >4 drinks/day or >14 drinks/week n Women (and > than 65 yrs) >3 drinks/day or >7 drinks/week n Increased risk of alcohol-related problems 4

5 What is a Drink? A standard drink is any drink that contains about 14 grams of pure alcohol (about 0.6 fluid ounces or 1.2 tablespoons) DSM5 - Substance Use Disorder n No longer need to differentiate between substance abuse and substance dependence n Each substance can be categorized as a disorder n Ex: Alcohol use disorder, stimulant use disorder, etc n Grade Severity: Mild, Moderate, Severe 5

6 DSM5 - Substance Use Disorder n 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: n Failure to fulfill role obligations n Recurrent substance use in situations that are physically hazardous n Persistent use despite social/interpersonal problems Criteria for Substance Use Disorder (contd) n Tolerance n Withdrawal n Using more than originally intended n Persistent desire or unsuccessful efforts to cut-down n Time spent obtaining/using substance or recovering from side effects n Reduction of social/occupational activities n Use despite physical/psychological problems n Craving n Need 2 criteria for SUD n 2-3 criteria =mild n 4-5 = moderate n >6 = severe 6

7 Screening U.S Preventive Services Task Force recommends screening all adult patients for alcohol misuse AND provide persons engaged in risky drinking with brief behavioral counseling interventions 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 Smith PC, et al. J Gen Intern Med 2009;24(7) NIAAA Guidelines

8 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 Evidence for the Single Screen Single question screen generally equal to other screenings (CAGE, AUDIT) 82-88% sensitivity for at-risk drinking % sensitivity for drug use disorder Smith PC, JGIM 2009; Smith PC, Arch Intern Med 2010 Saitz R et al. J Stud Alcohol Drugs,

9 A Positive Screen n What to do next? Assess n Determine how many drinks/day in a week n Ask which drugs the patient has been using n Ask about negative impacts The follow-up questions assess impact and determine whether he/she has a substance use disorder diagnosis. Determining At Risk vs. Substance Use Disorder n Pts who meet criteria for at-risk should get a brief intervention n Patients who meet substance use disorder criteria abuse should get a n Brief intervention AND n A referral to specialty care (if they are willing) AND n Be considered for pharmacotherapy 9

10 What is a Brief Intervention? n Short motivational interviews that encourage patients to create a plan of action that is based on their willingness to change their behavior n Non-judgmental, direct, honest feedback n If not ready to change harm reduction n Plan for follow-up Brief Intervention n You are drinking more than is medically safe n I strongly recommend that you cut down or quit and I m willing to help n Are you willing to consider making changes in your drinking? How to Help Patients: A Clinical Approach: NIAAA 2005 Resource for Clinicians 10

11 Motivational Interviewing n Express empathy, develop discrepancy, support self-efficacy n Tools: n Listen for change talk n Readiness to change ruler n Importance/confidence ruler Pharmacotherapy 11

12 Addiction Treatment Model: Treating Limbic Drive and Cortical Thinking Structures Decision Making (Counseling) From Pettinati, NIH 2006 Limbic Drive (Pharmacotherapy) Alcohol Use Disorder Pharmacotherapy Two Phases of Alcohol Use Disorder Treatment: n Acute Alcohol Withdrawal n Maintenance medications to reduce use or prevent relapse (FDA approved) n Disulfiram n n Acamprosate Naltrexone (oral and injectable) 12

13 Alcohol Relapse Prevention Meds: Disulfiram (Antabuse) n n n n n n Blocks alcohol metabolism (prevents acetaldehyde acetate); increase in blood acetaldehyde levels Antabuse reaction: flushing, weakness, nausea, tachycardia, hypotension VA Cooperative Study of Disulfuram in 605 men n High rate of non-compliance: 80% n If adherent, more likely to be abstinent Works best if given in monitored fashion Clinical Dose: 250mg daily (range mg/d) SE: Hepatotoxicity (check LFTs qmo x 3 then q3 mo) Fuller RK, et al. JAMA, 1986;256 Naltrexone for Alcohol Use Disorder n Similar structure to naloxone (Narcan) n Potent inhibitor of Mu opioid receptor binding n Endogenous opioids involved in the craving and reinforcing (pleasure) effects of alcohol 13

14 Naltrexone for Alcohol Use Disorder n Cochrane Review of NTX (based on 50 RCT) n Reduced risk of heavy drinking to 83% of the risk vs. placebo (RR 0.83; CI ) n Decreased drinking days by 4% n Not significant for return to any drinking (RR 0.96; CI ) n Estimate helps 1 out of 9 Srisurapanont & Jarusuraisin (2005) Cochrane Database Syst Rev Jan 25;(1):CD Pharmacotherapy of Alcohol Dependence: Naltrexone n Oral Naltrexone Hydrochloride n DOSE: 50 mg per day n Extended-Release Injectable Naltrexone (Vivitrol) n 380mg IM per month n Must be opioid-free for 7-10 days before starting n Contraindicated in liver failure or acute hepatitis Garbutt et al. JAMA,

15 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 effective 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,

16 Summary Alcohol Use Disorder n If abstinent: n Consider disulfiram as insurance (if monitored) n Consider naltrexone for relapse prevention n Can consider acamprosate n If still drinking n Consider naltrexone n If on opioids n Consider acamprosate Quiz n Which of the following is the most commonly misused class of prescription drugs? A. Opiates B. Stimulants C. Benzodiazepines 16

17 Rates of Prescription Medication Abuse Ages 12+ Non-Medical Use of Psychotherapeutics Ever Use 20.5% 5.6% Pain Medications 13.6% 3.9% Sedatives 3% 0.3% Use in Last Year (2014) DetTabs2014/NSDUH-DetTabs2014.pdf Prescription Opioid Abuse Unintentional US Overdoses n In 2007, one overdose death every 19 minutes n More than heroin and cocaine combined National Vital Statistics System. Available at 17

18 Source Where Pain Relievers Were Obtained for Most Recent Nonmedical Use among Past Year Users Aged 12 or Older: 2006 Source Where Respondent Obtained Drug Dealer/ Stranger More than 3.9% One Doctor 1.6% One Doctor 19.1% 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% Case n 64 yo woman presenting with c/o chronic osteoarthritis in both knees. X-rays are c/w OA. She has a h/o ulcer approximately 3 years ago. She says she needs something for pain as she is not interested in knee replacement. Do you: n A) Start her on acetaminophen with codeine n B) Refer her to orthopedics anyway n C) Start an NSAID with clear precautions on GI side effects n D) Try other treatment modalities (PT, tramadol) 18

19 Non-Cancer Pain n Complete hx and PE to evaluate pain n Agree on pain control goal and function goal n Consider non-medication options if appropriate n Lifestyle changes n Exercise, PT n Therapy, biofeedback n Alternative medicine: mindfulness, massage, acupuncture, etc Makris UE, et al. JAMA, 2014 How to Treat Non-Cancer Pain? n Consider non-opiate meds first n Tylenol, topical NSAIDS, NSAIDS n Neuropathic pain: gabapentin, TCAs (nortriptyline), pregabalin, lidocaine patch n Duloxetine (SNRI) n Muscle relaxants n Tramadol (weak affinity for Mu receptor) 19

20 Opioids for Non-Cancer Pain n Good evidence opioids help with acute pain in the short-term (<6 weeks) n No good evidence long-term opioids help with chronic (>3 mo) non-cancer pain n May cause harm (quality of evidence low) n Increased risk overdose, abuse, addiction, MI, fractures n 9940 patients on opioids >3 months n Risk of annual overdose 3.7X for 50-99mg/d morphine equivalent (0.7% annual overdose rate) n 8.9X for > 100mg/d (1.8% annual overdose rate) Chou R, Ann Intern Med, 2015; Dunn KM, Ann Intern Med, 2010 Opioid Dose and Risk for Overdose Daily Opioid dose (MSO4 eq) Hazard Ratio for OD (95% CI) None 0.31 ( ) 1 to <20 mg 1 20 to <50 mg 1.44 ( ) 50 to <100 mg 3.73 ( ) ( ) Any dose 5.16 ( ) Dunn et al Annals 20

21 What is a High Dose of an Opioid? n Cut-off is not exact n MSO4 50 mg is about the same as. n Codeine 60 mg q4h n Hydrocodone/APAP 10/300 5 times a day n Methadone 5 mg tid n Hydromorphone 4 mg tid n Oxycodone/APAP 10 mg/300 tid n Oxymorphone ER 7.5 mg bid n Fentanyl 25 mcg/hr patch Opioidcalculator.practicalpainmanagement.com Long vs. Short-Acting Opiates and Risk of Overdose Duration of Use Event Rates/ 10,000 person years LONG- ACTING Event Rates/ 10,000 person years SHORT- ACTING Hazard Ratio Any <14 days days Miller M, et al. JAMA Intern Med,

22 How To Balance Treating Pain with Risk* n ID factors for abuse n Opioid Risk Tool, Current Opioid Misuse Measure and others n Pain Agreement to discuss risks of opioids n Toxicology screening before prescribing and get old records n Get permission to talk to one family/friend who is NOT on opiates *For all patients Building a Patient-Provider Agreement 22

23 The PEG tracks benefits of opioids On a scale of 0-10, over the last week: What has your average pain been? (0-10) How much has your pain interfered with your enjoyment of life? (0-10) How much has your pain interfered with your general activity? (0-10) Krebs, 2009 Using Opiates for Non-Cancer Pain n Avoid concomitant benzos/sedative-hypnotics n Check medication list for interactions (esp methadone) n Initiate with short-acting low dose n Don t increase more frequently than q2 weeks n Document pain score and function each visit (PEG) n Avoid escalating doses above mg/d morphine equivalent doses 23

24 How To Balance Treating Pain with Opioid Risk? n Compliance monitoring n Pill counts, Utox, CURES reports n Watch for aberrant behaviors n Unsanctioned use, drug seeking behaviors, rx losses, etc n Re-assess function and goals at each visit n Check last dosing (for Utox) Urine Drug Testing n Test everyone, with frequency standardized according to risk. n Morphine equiv 200 mg+ or recent aberrancy: monthly n mg: quarterly n mg: annually 24

25 Urine Toxicology Results Drug Window of Detection 3 (Days) Medications that Cause False Positives (Common Examples) Amphetamine 1-3 days Bupropion, ciprofloxacin, ephedrine, labetalol, melatonin, metoprolol, phenylephrine, pseudoephedrine, ranitidine, sertraline. Confirmatory Testing Available for Screening Test? Yes Benzodiazepines* 1-7 days (2-30 days for diazepam) Diphenhydramine, gemfibrozil, hydroxyzine, indomethacin, sertraline, trazodone Cocaine 1-3 days - No Methadone 3-10 days - No Opiates (only codeine, morphine, heroin) 1-3 days Fluoroquinolones, quinine, poppy seeds, rifampin Yes** Yes Oxycodone 1-2 days Codeine, hydrocodone, hydromorphone, oxymorphone Yes Adapted from UCSF Outpatient Handbook,

26 Urine Toxicology Results n If concern for tampering, order urine creatinine (should be >20) n ALWAYS cause opiate screen to be positive? n Heroin, morphine, codeine n SOMETIMES cause opiate screen to be positive? n Hydrocodone, hydromorphone, oxycodone, oxymorphone n NEVER cause opiate screen to be positive? n Buprenorphine, fentanyl, meperidine, methadone, tramadol n Check fentanyl immunoassay or methadone screen Steiger S, Drug Testing FAQ When to Taper Prescription Opioids (Non-Cancer Pain)? n When risks > benefits n Aberrant behaviors n If multiple agents, convert to morphine equivalents to calculate total dose n n Reduce long-acting agents first vs. convert to shortacting and taper 26

27 When to Taper Prescription Opioids (Non-Cancer Pain)? n Slow Taper: reduce dose by 10%/month n Minimizes withdrawal sx n Rapid Taper n Remove 10-15%/week n Indications: substance abuse, loss of control over pill use n Consider referral for substance abuse counseling/ treatment n Immediate Cessation n Overdose, suicide attempt, rx forgery, diversion, other threats Reducing Risk for All Patients Which of the following interventions has been demonstrated to reduce rates of overdose in patients prescribed opioids for chronic non-cancer pain? a) Implementing pill count visits b) Random urine toxicology testing c) Tapering them to lower doses d) Prescription of naloxone 27

28 Reducing risk for all patients n Reduction in OD among heroin users since late 90 s n Project Lazarus in NC showed decrease in opioid OD from 47 to 29 per 100,000* n palliative/ *Albert et al., Pain Med CA.Detailing_Provider_final.pdf 28

29 Pharmacotherapies for Opiate Dependence Methadone Buprenorphine Naltrexone Opioid Dependence Maintenance Therapy: Methadone Can only be prescribed through a registered narcotic treatment program Long acting mu agonist (24-36h) mg will block withdrawal, but not craving mg is more effective at reducing opioid use than lower doses (e.g.: mg/d) Interacts with LOTS of medications QT prolongation (approx 2%) Strain EC, et al. JAMA,

30 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) Buprenorphine DEA certification required to prescribe (8 hrs of training) 30

31 Opioid Dependence Therapy: Antagonist Treatment (Naltrexone) n Prevent impulsive use of drug n Relapse rates high (90%) following detoxification with no medication treatment n Dose (oral): 50 mg daily, 100 mg every 2 days, 150 mg every third day n Dose (IM): 380mg IM q month n Side effects: hepatotoxicity, monitor liver function tests every 3 months n Biggest issue is lack of compliance Take Home Points At-risk and substance use disorders common Three medications FDA-approved for the maintenance treatment of alcoholism n Prescription opioids high abuse/misuse potential n Consider non-opioid treatments for chronic noncancer pain n Ongoing monitoring required for opioid prescribing 31

32 Thank You! n Special thanks to Scott Steiger, MD, UCSF Division of General Internal Medicine n Resources n Local mutual help groups n (resources) n n Substance Abuse Facility Treatment Locator Website n n 32

33 Substance Use Disorders Selected References Katherine Julian, MD December 2015 Ballantyne JC et al. Opioid therapy for chronic pain. N Eng J Med, 2003;349: Bema C, et al. Tapering long-term opioid therapy in chronic non cancer pain: evidence and recommendations for everyday practice. Mayo Clin Proc, 2015;90(6): Bradley K et al. Brief approaches to alcohol screening: practical alternatives for primary care. J Gen Intern Med, 2009;24(7): Britt GC and McCance-Katz EF. A brief overview of the clinical pharmacology of club drugs. Substance Use and Misuse, 2005;40: Byrne PR et al. Brief intervention for problem drug use in safety-net primary care settings. JAMA, 2014;312(5): Centers for Disease Control and Prevention. CDC grand rounds: prescription drug overdoses a U.S. epidemic. MMWR, January 13, 2012 / 61(01); Chou R, et al. The effectiveness and risks of long-term opioid therapy for chronic pain: a systematic review for a national institutes of health pathways to prevention workshop. Ann Intern Med, 2015; 162(4): Curry SJ et al. At-risk drinking among patients making routine primary care visits. Preventive Medicine, 2000;31: Esser MB, Hedden SL, et al. Prevalence of Alcohol Dependence Among US Adult Drinkers, Prev Chronic Dis 2014;11. Fiellin DA, et al. Primary care-based buprenorphine taper vs. maintenance therapy for prescription opioid dependence. JAMA Intern Med, 2014;174(12): Franklin GM. Opioids for chronic noncancer pain. American Academy of Neurology, 2014;83: Garbutt JC et al. Efficacy and tolerability of long-acting injectable naltrexone for alcohol dependence. JAMA, 2005;293: Garbutt JC. The state of pharmacotherapy for the treatment of alcohol dependence. Journal of Substance Abuse and Treatment, 2009;36:S15-S23.

34 Gordon A, et al. Prescribing opioids for chronic noncancer pain in primary care: risk assessment. Postgraduate Medicine, September 2014;126(5): Hill KP et al. Diagnosing and treating opioid dependence. J Fam Pract Oct;61(10): Makris UE, et al. Management of persistent pain in the older adult. JAMA, 2014;312(8): McCance-Katz EF. Office-based buprenorphine treatment for opioid-dependent patients. Harv Rev Psychiatry, 2004;12: Merrill JO and Duncan MH. Addiction disorders. Med Clin N Am, 2014;98: Miller M, Barber CW, et al. Prescription opioid duration of action and the risk of unintentional overdose among patients receiving opioid therapy. JAMA Intern Med, 2015;175: National Institute on Alcohol Abuse and Alcoholism. Helping patients who drink too much: a clinician's guide National Institute on Drug Abuse. (accessed 2/2/2011) Nicholls L, et al. Opioid dependence treatment and guidelines. J Manag Care Pharm, 2010;16(1-b):S14-S21. Rosner RS, et al. Acamprosate for alcohol dependence (review). The Cochrane Collaboration Rosner RS, et al. Opioid antagonists for alcohol dependence (review). The Cochrane Collaboration Rubak S et al. Motivational interviewing: a systematic review and meta-analysis. British Journal of General Practice, 2005;55: Saitz R, et al. Screening and brief intervention for drug use in primary care: the aspire randomized clinical trial. JAMA, 2014;312(5): Saitz R, et al. The ability of single screening questions for unhealthy alcohol and other drug use to identify substance dependence in primary care. J Stud Alcohol Drugs, 2014; 75: Smith PC et al. A single-question screening test for drug use in primary care. Arch Intern Med, 2010;170(13): Smith PC et al. Primary care validation of a single-question alcohol screening test. J Gen Intern Med, 2009;24(7):

35 Vasilaki EI et al. The efficacy of motivational interviewing as a brief intervention for excessive drdinking: a meta-analytic review. Alcohol & Alcoholism, 2006;41(3): Wu LT and Blazer DG. Illicit and nonmedical drug use among older adults: a review. Journal of Aging and Health, 2010.