Decreasing Alcohol Use with Medications: What Works?

Decreasing Alcohol Use with Medications: What Works? Annual Review of Family Medicine December 7 th, 2017, UCSF Mission Bay Ben Smith, MD MPH Assistant Professor of Family and Community Medicine San Francisco General Hospital Family and Community Medicine Residency Program National Clinician Consultation Center Substance Use Warmline

Decreasing Alcohol Use with Medications: What Works? Annual Review of Family Medicine December 7 th, 2017, UCSF Mission Bay Ben Smith, MD MPH Assistant Professor of Family and Community Medicine San Francisco General Hospital Family and Community Medicine Residency Program National Clinician Consultation Center Substance Use Warmline I have no financial disclosures or conflicts of interest to report

Objectives Review diagnostic criteria for alcohol use disorder (DSM-V) Review Evidence Base for Pharmacotherapy of AUD (reducing use). Touch on outpatient treatment of alcohol withdrawal. NIAAA, USDA

DSM 5 Criteria for Alcohol Use Disorder AUD Severity: - Mild: 2-3 Sxs harmful use - Moderate: 4-5 Sxs dependence - Severe: 6+ Sxs dependence Saitz R Unhealthy alcohol use N Engl J Med 2005;352596-607

Alcohol Use Disorder-Screening Single-item screening is preferred: How many times in the past year have you had five or more (for men) or four or more (for women) drinks in a day? An initial question can be Do you sometimes drink beer, wine, or other alcoholic beverages? Ries, R. K., Fiellin, D. A., Miller, S. C., & Saitz, R. (2014). The ASAM principles of addiction medicine. Lippincott Williams & Wilkins. NIAAA. Clinicians Guide to Helping Patients Who Drink Too Much, 2007.

Pharmacotherapy: Patient Selection Moderate to severe alcohol use disorder? Not drinking but craving? Contraindications? Interested in treatment? O'malley, Stephanie S., et al. "Initial and maintenance naltrexone treatment for alcohol dependence using primary care vs specialty care: a nested sequence of 3 randomized trials." Archives of Internal Medicine 163.14 (2003): 1695-1704.

Pharmacotherapy: Which Medications? Jonas, Daniel E., et al. "Pharmacotherapy for adults with alcohol use disorders in outpatient settings: a systematic review and meta-analysis." Jama 311.18 (2014): 1889-1900.

Pharmacotherapy: 1 st Line Medication Studies Effect Size Strength of Evidence Acamprosate 16 RCTs -0.14 to -0.04 Moderate Jonas, 2014

Pharmacotherapy: 1 st Line Medication Studies Effect Size Strength of Evidence Acamprosate 16 RCTs -0.14 to -0.04 Moderate Disulfiram 2 RCTs -0.11 to 0.03 Low Jonas, 2014

Pharmacotherapy: 1 st Line Medication Studies Effect Size Strength of Evidence Acamprosate 16 RCTs -0.14 to -0.04 Moderate Disulfiram 2 RCTs -0.11 to 0.03 Low Naltrexone 16 RCTs -0.10 to -0.02 Moderate Jonas, 2014

Pharmacotherapy: Evidence Base Medications for Alcohol Strong Evidence- 20+ RCTs Acamprosate Naltrexone Some Evidence (7-11 RCTs) Disulfiram Topirimate Limited Evidence Gabapentin Ondansetron Gabapentin Varenicline Buspirone Jonas, 2014

Pharmacotherapy: Evidence Base Medications for Alcohol Strong Evidence- 20+ RCTs Acamprosate (22) Naltrexone (40) Some Evidence (7-11 RCTs) Disulfiram (4) Topirimate Limited Evidence Gabapentin Ondansetron Gabapentin Varenicline Buspirone FDA Approved (RCT #) Jonas, 2014

Pharmacotherapy: Disulfiram Disulfiram High Dose Disulfiram Low Dose, Placebo P>0.05 Richard K. Fuller, Laure Branchey, Dennis R. Brightwell, Robert M. Derman, Chad D. Emrick, Frank L. Iber, Kenneth E. James, Roy B. Lacoursiere, Kelvin K. Lee, Ilse Lowenstam, Iradj Maany, Dewey Neiderhiser, James J. Nocks, Spencer Shaw. Disulfiram Treatment of AlcoholismA Veterans Administration Cooperative Study. JAMA. 1986;256(11):1449 1455.

Pharmacotherapy: Disulfiram Because of its long-standing availability, clinicians may be more familiar with disulfiram than naltrexone or acamprosate. However, well-controlled trials of disulfiram did not show overall reductions in alcohol consumption. In a subgroup analysis of the largest disulfiram trial, there were fewer drinking days for patients who returned to drinking and had a complete set of assessments. Jonas 2014 Jonas 2014

Pharmacotherapy: Naltrexone and Acamprosate Naltrexone + Acamprosate Naltrexone Acamprosate Placebo Kiefer, Falk, et al. "Comparing and combining naltrexone and acamprosate in relapse prevention of alcoholism: a double-blind, placebo-controlled study." Archives of general psychiatry 60.1 (2003): 92-99.

Pharmacotherapy: Naltrexone and Acamprosate Naltrexone + Acamprosate Naltrexone Acamprosate Placebo Kiefer2003

Pharmacotherapy: 1 st Line Specifics Dosing, Side Effects Medication Dose Contraindication Side Effects Acamprosate 666 mg TID Renal Insufficiency GI Distress Naltrexone 50 mg Daily Liver**, Opioids GI Distress Disulfiram 500 mg/day Recent EtOH Neuropathy Jonas, 2014

Pharmacotherapy: Topiramate? Stay Tuned Baltieri, D. A., Daró, F. R., Ribeiro, P. L. and De Andrade, A. G. (2008), Comparing topiramate with naltrexone in the treatment of alcohol dependence*. Addiction, 103: 2035 2044.

Pharmacotherapy: Topiramate? Stay Tuned Medication Dose Contraindication Side Effects Topiramate 300 mg Daily None Sedation Baltieri, D. A., Daró, F. R., Ribeiro, P. L. and De Andrade, A. G. (2008), Comparing topiramate with naltrexone in the treatment of alcohol dependence*. Addiction, 103: 2035 2044.

Outpatient Alcohol Withdrawal Treatment

EtOH Withdrawal: Patient Selection Asplund, Chad A., Jacob W. Aaronson, and Hadassah E. Aaronson. "3 regimens for alcohol withdrawal and detoxification." Journal of family practice 53.7 (2004): 545-545.

EtOH Withdrawal: Patient Selection Asplund 2004

EtOH Withdrawal: Pharmacotherapy Outpatient Treatment Protocols Long acting, smoother course Asplund 2004

EtOH Withdrawal: Pharmacotherapy Outpatient Treatment Protocols Shorter acting, more attention to timing needed, better in hepatic dysfunction Asplund 2004

EtOH Withdrawal: Pharmacotherapy Outpatient Treatment Protocols Needs rapid dose escalation (zzz), used widely in Europe, but no RCTs showing seizure or delerium tremens prevention. Asplund 2004

EtOH Withdrawal: Gabapentin, Stay Tuned Myrick, Hugh, et al. "A Double Blind Trial of Gabapentin Versus Lorazepam in the Treatment of Alcohol Withdrawal." Alcoholism: Clinical and Experimental Research 33.9 (2009): 1582-1588.

Thank You! Asplund, Chad A., Jacob W. Aaronson, and Hadassah E. Aaronson. "3 regimens for alcohol withdrawal and detoxification." Journal of family practice 53.7 (2004): 545-545. Baltieri, D. A., Daró, F. R., Ribeiro, P. L. and De Andrade, A. G. (2008), Comparing topiramate with naltrexone in the treatment of alcohol dependence*. Addiction, 103: 2035 2044. Jonas, Daniel E., et al. "Pharmacotherapy for adults with alcohol use disorders in outpatient settings: a systematic review and meta-analysis." Jama 311.18 (2014): 1889-1900. Kiefer, Falk, et al. "Comparing and combining naltrexone and acamprosate in relapse prevention of alcoholism: a double-blind, placebo-controlled study." Archives of general psychiatry 60.1 (2003): 92-99. Myrick, Hugh, et al. "A Double Blind Trial of Gabapentin Versus Lorazepam in the Treatment of Alcohol Withdrawal." Alcoholism: Clinical and Experimental Research 33.9 (2009): 1582-1588. O'malley, Stephanie S., et al. "Initial and maintenance naltrexone treatment for alcohol dependence using primary care vs specialty care: a nested sequence of 3 randomized trials." Archives of Internal Medicine 163.14 (2003): 1695-1704. Ries, R. K., Fiellin, D. A., Miller, S. C., & Saitz, R. (2014). The ASAM principles of addiction medicine. Lippincott Williams & Wilkins. NIAAA. Clinicians Guide to Helping Patients Who Drink Too Much, 2007. Richard K. Fuller, Laure Branchey, Dennis R. Brightwell, Robert M. Derman, Chad D. Emrick, Frank L. Iber, Kenneth E. James, Roy B. Lacoursiere, Kelvin K. Lee, Ilse Lowenstam, Iradj Maany, Dewey Neiderhiser, James J. Nocks, Spencer Shaw. Disulfiram Treatment of AlcoholismA Veterans Administration Cooperative Study. JAMA. 1986;256(11):1449 1455. Saitz R Unhealthy alcohol use N Engl J Med 2005;352596-607 Thank you!

Cases: Alcohol Pharmacotherapy

Case #1 42 y/o female, HIV neg, HTN, drinks unknown quantity of vodka daily. Has Anxiety and PTSD from murder of son 4 years ago. Was hospitalized recently after drinking 1 bottle of vodka and becoming unconscious. History of crack use but has not used crack for many, many years. Accessed NA or AA for crack use. Amlodipine 10mg Pantoprazole 40mg Imipramine 25mg Nicotine patch Ondansetron HCl 4 Past Behavioral Interventions: Past AA and NA attendance. Has gone to grief groups in the past, which did help with grief and loss over son's deaths. Question: how do I reduce this patient s drinking?

Case #2 48 y/o female interested in outpatient detox. Drinks 1/2 bottle of hard alcohol (unknown type). Nauseous with tremors in AM prior to drinking. CIWA score 13. Motivated to stop drinking. First alcohol use was after husband's death 1 year ago. She has HTN, anxiety, Major Depressive Disorder. No other substance use reported. Currently enrolled in psychiatry. She has never tried AA. Buspar 10mg BID HCTZ 25 mg QD Losartan 25 QD Labs: ALT 73 AST 102, macrocytic anemia MCV 108 Hg 15.9 Hct 47.9 Question: Is outpatient detoxification appropriate for this patient?