1. Identification and Treatment of Alcohol Use Disorders in Primary Care Valerie Carrejo, MD Resident school 8/31/2016

2. Objectives Know who to screen for alcohol use in the primary care setting Know how to screen for and interpret screening for at risk drinking and alcohol use disorders in the primary care setting Know how to start a conversation about alcohol use in patients who may drink too much Know how to identify patients who may need medication assisted treatment for their alcohol use disorder Know the three FDA approved medications for treating alcohol use disorders in the outpatient setting Review other medications that may be beneficial for treating alcohol use disorders in the outpatient setting

3. Do you know this patient? 54 yo male with a history of hepatitis C and alcohol use who is admitted to the family medicine service after having a witnessed seizure. The patient says “my doctor told me to quit drinking because I have cirrhosis”

4. Alcohol use affects us all

5. Why should we care?

6. We all know it is a problem Excessive alcohol use can increase a person’s risk of developing serious health problems in addition to those issues associated with intoxication behaviors and alcohol withdrawal symptoms. Many Americans begin drinking at an early age. In 2012, about 24% of eighth graders and 64% of twelfth graders used alcohol in the past year. http://www.samhsa.gov/disorders/substance-use

7. Short-term health risks Injuries, such as motor vehicle crashes, falls, drownings, and burns Violence, including homicide, suicide, sexual assault, and intimate partner violence Alcohol poisoning, a medical emergency that results from high blood alcohol levels Risky sexual behaviors, including unprotected sex or sex with multiple partners STDs Unintended pregnancies Still births, miscarriage and fetal alcohol syndrome http://www.cdc.gov/alcohol/fact-sheets/alcohol-use.htm

8. Long-term health risks High blood pressure, heart disease, stroke, liver disease, and digestive problems Cancer of the breast, mouth, throat, esophagus, liver, and colon Learning and memory problems, including dementia and poor school performance Mental health problems, including depression and anxiety. Social problems, including lost productivity, family problems, and unemployment Alcohol dependence, or alcoholism http://www.cdc.gov/alcohol/fact-sheets/alcohol-use.htm

9. National statistics According to the Centers for Disease Control and Prevention (CDC), excessive alcohol use causes 88,000 deaths a year. National Survey on Drug Use and Health (NSDUH) slightly more than half (52.7%) of Americans ages 12 and up reported being current drinkers of alcohol. Most people drink alcohol in moderation. However, of those 176.6 million alcohol users, an estimated 17 million have an AUD.

10. New Mexico In 2007, the estimated cost of excessive alcohol consumption in New Mexico was more than $2.8 billion, or $1,400 per person.* Over the last 15 years, New Mexico’s death rate for alcohol related injury has consistently been among the worst in the nation ranging from 1.4 to 1.8 times the national rate.* Over the past 25 years, New Mexico’s rate of Alcohol-related Chronic Liver Disease (AR-CLD) has increased 14% while the national rate has decreased 24%.** Since 1998, the death rate from AR-CLD has been 45-50% higher than the death rate from alcohol-related motor vehicle crashes.** *The State of Health in New Mexico 2013, NM Dept of Health **New Mexico Substance Abuse Epidemiology Profile, New Mexico Department of Health, October 2010

11. Who do we treat? Only about 13 percent of persons with alcohol dependence receive specialized addiction treatment Only 24 percent seek any kind of help. Only the most severely dependent drinkers attend alcohol rehabilitation programs. For those who do, there is a 10-year gap between the onset of the disorder (21 years of age, on average) and first treatment.

12. When use becomes a disorder Problem drinking that becomes severe is given the medical diagnosis of “alcohol use disorder” or AUD. Approximately 7.2 percent or 17 million adults in the United States ages 18 and older had an AUD in 2012. 11.2 million men and 5.7 million women. An estimated 855,000 adolescents ages 12–17 had an AUD. Unfortunately, only of a fraction of people who could benefit from treatment receive help. In 2012, 1.4 million adults received treatment for an AUD at a specialized facility (8.4 percent of adults in need). This included 416,000 women (7.3 percent of women in need) and 1.0 million men (8.9 percent of men in need). https://www.niaaa.nih.gov/alcohol-health/overview-alcohol- consumption/alcohol-use-disorders https://www.niaaa.nih.gov/alcohol-health/overview-alcohol- consumption/alcohol-use-disorders

13. Who should we screen?

14. USPSTF Adults age 18 and older The USPSTF recommends that clinicians screen ALL adults aged 18 years or older for alcohol misuse and provide persons engaged in risky or hazardous drinking with brief behavioral counseling interventions to reduce alcohol misuse. Grade B recommendation Adolescents The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening and behavioral counseling interventions in primary care settings to reduce alcohol misuse in adolescents Grade I statement

15. How should we screen?

16. One question “Do you drink alcohol?” Then move on if the answer is yes

17. How should we screen? The USPSTF recommends one of the following tools AUDIT questionnaire Abbreviated AUDIT-Consumption Single Question of alcohol use “How many times in the past year have you had five (for men) or four (for women and all adults older than 65 years) or more drinks in a day?” This single-question screen has been shown to be as sensitive and specific as other screening methods

18. Standard Drink

20. Counsel all patients who drink Advise to stay within recommended limits For healthy men up to age 65— no more than 4 drinks in a day AND no more than 14 drinks in a week For healthy women (and healthy men over age 65)— no more than 3 drinks in a day AND no more than 7 drinks in a week Recommend lower limits or abstinence as medically indicated; for example, for patients who take medications that interact with alcohol have a health condition exacerbated by alcohol are pregnant (advise abstinence) Express openness to talking about alcohol use and any concerns it may raise Rescreen annually

21. Levels of consumption Moderate Drinking—According to the Dietary Guidelines for Americans, moderate drinking is up to 1 drink per day for women and up to 2 drinks per day for men. Binge Drinking— SAMHSA defines binge drinking as drinking 5 or more alcoholic drinks on the same occasion on at least 1 day in the past 30 days. The National Institute on Alcohol Abuse and Alcoholism (NIAAA) defines binge drinking as a pattern of drinking that produces blood alcohol concentrations (BAC) of greater than 0.08 g/dL. This usually occurs after 4 drinks for women and 5 drinks for men over a 2 hour period. Heavy Drinking—SAMHSA defines heavy drinking as drinking 5 or more drinks on the same occasion on each of 5 or more days in the past 30 days.

22. Alcohol Use Disorder More than moderate, binge or heavy drinking May require more specific questioning Use DSM criteria to help decide

25. Risky Drinking State your concern and recommendation clearly “You are drinking more than is medically safe” “I encourage you to cut back or quit drinking” “Are you willing to consider making this change?” Helping Patients Who Drink Too Much

26. Is the patient ready to change? NO Don’t be discouraged Restate your concern Encourage reflection Reaffirm your willingness to help YES Help set goals Agree on a plan Specific steps/goals How will it be tracked Arrange follow up Provide tools Offer referral for counseling

27. Behavioral support Counseling Cognitive behavioral therapy Motivational enhancement therapy Marital and family therapy Brief Interventions Mutual Help Groups Alcoholics anonymous Other 12-step programs Al Anon- for family members Online recovery services SMART Recovery Life Process Program

28. Behavioral Health Supports Developing the skills needed to stop or reduce drinking Helping to build a strong social support system Working to set reachable goals Coping with or avoiding the triggers that might cause relapse

29. Your patient likely has AUD, now what?

30. Laboratory evaluation CBC Mean corpuscular volume (MCV) may be elevated in alcohol induced macrocytic anemia Platelets may be suppressed in heavy drinkers Liver function testing AST commonly elevated over ALT Elevated GGT plus elevated AST has high specificity for heavy alcohol use Chemistry Assess renal function and glucose HIV, HCV and other STD testing Pregnancy test in women

31. Assess for risk of alcohol withdrawal Definitions of withdrawal: Simple Withdrawal: Sweating, tremor, anxiety, palpitations Complicated Withdrawal: Seizure or Delirium Tremens Risk factors for ANY withdrawal: Former history of withdrawal Conscious with a B.A.L. over 0.3 % by volume Risk factors for complicated withdrawal: Former history of withdrawal seizure or Delirium Tremens Traumatic brain injury Acute illness (increases the likelihood of DTs)

32. Consider acute detoxification Inpatient detoxification is recommended if risk for significant alcohol withdrawal Outpatient management of alcohol withdrawal May be fixed schedule or symptom triggered Chlordiazepoxide taper (Librium) Metabolized by the liver Do not use if suspect significant liver disease Lorazepam taper (Ativan) Oxazepem taper (Serax)

33. Medication Assisted Treatment There are 4 medications have been FDA approved for MAT for alcohol use disorder Three oral medications Disulfuram (Antabuse) Naltrexone (Depade, ReVia) Acamprosate (Campral) One long acting injectable medication Extended release injectable naltrexone (Vivitrol)

34. Disulfiram Usual adult dosage Oral dose: 250mg daily (range 125mg to 500mg) Do not take for at least 12 hours after last drink Action Inhibits immediate metabolism of alcohol Build up of acetaldehyde causes flushing, nausea, sweating and tachycardia Contraindications Concomitant use of alcohol containing products Coronary artery disease Hypersensitivity to rubber derivatives Precautions Hepatic cirrhosis, cerebral vascular disease, psychosis, diabetes, epilepsy, hypothyroidism, renal impairment, pregnancy

35. Disulfiram Serious adverse reactions Disulfiram-alcohol reaction Hepatotoxicity Optic neuritis Peripheral neuropathy Psychotic reactions Common side effect Metallic after-taste Dermatitis Transient drowsiness

36. Naltrexone Usual adult dosing 50 mg daily oral dose 380mg IM monthly dose Patient must be opioid free for 7-10 days prior to first dose Action Blocks opioid receptors resulting in reduced craving and reduced reward to drinking Patient cuts back on alcohol use over time Contraindications Currently using opioids or in acute opioid withdrawal Anticipated need for opioid analgesics Acute hepatitis or liver failure

37. Naltrexone Precautions Hepatic disease, renal impairment, suicide attempt or depression, pregnancy Serious adverse reactions Will precipitate severe opioid withdrawal if patient is dependent on opioids Hepatotoxicity (not at recommended doses) Common side effect Nausea, vomiting, decreased appetite Headache, dizziness Fatigue, somnolence Anxiety

38. Acamprosate Usual adult dosing 666mg (two 333mg tablets) three times per day Renal impairment (CrCl 30-50 mL/min) reduce dose to 333mg three times per day Action Affects glutamate and GABA neurotransmitter systems Contraindications Severe renal impairment (CrCl <30mL/min)

39. Acamprosate Precautions Moderate renal impairment, reduce dose to 333mg TID Depression or suicidal ideation and behavior Pregnancy Serious adverse reactions Rare events of suicidal ideation and behavior Common side effect Diarrhea Somnolence

40. Other pharmaceutical options may be coming

41. Gabapentin Mason, BJ et al. “Gabapentin Treatment for Alcohol Dependence: A Randomized Controlled Trial” JAMA Intern Med. 2014;174(1):70-77. Importance: Approved medications for alcohol dependence are prescribed for less than 9% of US alcoholics. Objective: To determine if gabapentin, a widely prescribed generic calcium channel/γ-aminobutyric acid–modulating medication, increases rates of sustained abstinence and no heavy drinking and decreases alcohol-related insomnia, dysphoria, and craving, in a dose-dependent manner.

42. Gabapentin Design, Participants and Setting: A 12-week, double-blind, placebo-controlled, randomized dose-ranging trial of 150 men and women older than 18 years with current alcohol dependence, conducted from 2004 through 2010 at a single- site, outpatient clinical research facility adjoining a general medical hospital. Interventions: Oral gabapentin (dosages of 0 [placebo], 900 mg, or 1800 mg/d) and concomitant manual-guided counseling. Main Outcomes and Measures: Rates of complete abstinence and no heavy drinking (coprimary) and changes in mood, sleep, and craving (secondary) over the 12-week study.

43. Gabapentin Results: Gabapentin significantly improved the rates of abstinence and no heavy drinking. The abstinence rate was 4.1% in the placebo group, 11.1% in the 900-mg group, and 17.0% in the 1800-mg group The no heavy drinking rate was 22.5% in the placebo group, 29.6% in the 900-mg group, and 44.7% in the 1800-mg group Similar linear dose effects were obtained with measures of mood, sleep, and craving There were no serious drug-related adverse events, and terminations owing to adverse events, time in the study, and rate of study completion did not differ among groups.

44. Gabapentin Conclusions and Relevance Gabapentin (particularly the 1800-mg dosage) was effective in treating alcohol dependence and relapse-related symptoms of insomnia, dysphoria, and craving, with a favorable safety profile. Increased implementation of pharmacological treatment of alcohol dependence in primary care may be a major benefit of gabapentin as a treatment option for alcohol dependence.

45. Baclofen- may be useful Rigal, L, et al. “Abstinence and ‘Low-Risk’ Consumption 1 Year after the Initiation of High-Dose Baclofen: A Retrospective Study among ‘High Risk’ Drinkers. Alcohol and Alcoholism Vol 47, No. 4, pp. 439-442, 2012. DOI: http://sx.doi.ort/10.1093/alcalc/ags028http://sx.doi.ort/10.1093/alcalc/ags028 Aim To assess the proportions of “high risk” drinkers’ abstinent or with “low-risk” consumption levels 1 year after the initiation of high dose baclofen Methods Retrospective open study Outcome was to assess the level of alcohol consumption in the 12 th month of treatment

46. Baclofen- continued Results 132 or 181 patients completed study After 1 year, 80% of the 132 were either abstinent (n=78) or drinking at low risk levels (n=28) in their 12 th month of treatment Mean baclofen dose was 129 +/- 71mg/day Conclusion High-dose baclofen should be tested in randomized placebo- controlled trials among high risk drinkers.

47. References CDC http://www.cdc.gov/alcohol/fact-sheets/alcohol-use.htmhttp://www.cdc.gov/alcohol/fact-sheets/alcohol-use.htm ECHO ACCESS: Alcohol Use Disorder Protocol Mason, BJ et al. “Gabapentin Treatment for Alcohol Dependence: A Randomized Controlled Trial” JAMA Intern Med. 2014;174(1):70-77. Rigal, L, et al. “Abstinence and ‘Low-Risk’ Consumption 1 Year after the Initiation of High-Dose Baclofen: A Retrospective Study among ‘High Risk’ Drinkers. Alcohol and Alcoholism Vol 47, No. 4, pp. 439- 442, 2012. National Institute on Alcohol use and Alcoholism https://www.niaaa.nih.gov/alcohol-health/overview-alcohol- consumption/alcohol-use-disorders https://www.niaaa.nih.gov/alcohol-health/overview-alcohol- consumption/alcohol-use-disorders SAMSHA http://www.samhsa.gov/disorders/substance-usehttp://www.samhsa.gov/disorders/substance-use Willenbring, ML, et al. “Helping Patients Who Drink to Much: An Evidence Based Guide for Primary Care Physicians” Am Fam Physician. 2009;80(1):44-50.

48. Questions?