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Pharmacologic Treatment of Alcohol Use Disorder

Michael Baca Atlas, MD and Neda Frayha, MD
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How much do we really know about the pharmacologic treatment of alcohol use disorder? After this segment with Dr. Michael Baca-Atlas and our own Neda Frayha, the answer will be, a whole lot.

 

Pearls:

  • Fewer than 10% of adults with alcohol use disorder (AUD) receive pharmacotherapy due to lack of familiarity and perceived efficacy of FDA-approved medications.

  • FDA-approved medications for AUD include disulfiram, acamprosate and naltrexone (oral and IM). Non-FDA approved medications with proven efficacy that are also recommended include gabapentin and topiramate.

 

  • Demographics:

    • 15 million people in the US have alcohol use disorder (AUD) and 88,000 people die annually

    • Fewer than 10% of adults with AUD received pharmacotherapy to treat it due to lack of familiarity and perceived efficacy of FDA approved medications

  • Definition:

    • No longer alcohol dependence or abuse → those terms went away with DSM-5 in 2013

    • Per DSM-5 there are 11 criteria of which you only need to meet 2 criteria:

    • Rethinking Drinking Campaign: online tool where providers can can show patients how much they are drinking, the financial implications and the harms

  • Treatment:

    • 1. Disulfiram:

      • FDA approved in 1951

      • Inhibits aldehyde dehydrogenase resulting in higher levels of acetaldehyde leading to the disulfiram ethanol reaction. This can lead to vital sign instability, cardiovascular collapse and even seizures (usually associated with higher doses).

      • Does not take away their alcohol cravings

      • Useful for patient interested in abstaining from alcohol 100% and in a setting where adherence to the med can be controlled

      • Must stop drinking for 24 hours before taking

      • The disulfiram-ethanol reaction can occur up to 2 weeks after stopping the medication

      • Start with 500mg daily for 1-2 weeks and then follow by 250mg daily

      • Not a good option for patients with other significant medical comorbidities

      • Hand sanitizer or ethanol found in small food products may trigger this reaction

    • 2. Acamprosate:

      • FDA approved in 2004

      • Gaba receptor agonist and NMDA receptor antagonist

      • Good in situation where person is in a post detox state because it can help with protracted withdrawal, does not have to 100% abstinent

      • Renally cleared

      • Dose 666mg TID, which can be hard for patients to remember

    • 3. Naltrexone (PO):

      • FDA approved in 1994

      • Mu-opioid receptor antagonist

      • No adverse reaction if currently drinking alcohol

      • Shown to prevent relapse to heavy drinking, reduced craving and overall drinking days

      • Dose at 25mg daily and increase up to 100mg, although FDA approved dose is 50mg

      • Check liver function and urine tox to ensure no concurrent opioid use

      • Should not use any opioids within last 7 days (short-acting) to 14 days (long-acting)

    • 4. Naltrexone (IM):

      • Shown to reduce heavy drinking by 25% and also effective at improving days of abstinence

      • Costly for uninsured at $1400 per month

      • 380mg monthly IM

      • Works well to reduce cravings

      • Continue for at least 6-12 months

    • 5. Gabapentin:

      • non-FDA approved, reserved for moderate to severe AUD

      • Gaba agonist

      • About a 20% misuse rate in studies where people use it at high enough doses for anxiolytic effect or even to get high

      • For use in protracted or subacute withdrawal symptom management

      • May be used in combination with naltrexone

    • 6. Topiramate:

      • non-FDA approved, reserved for moderate to severe

      • Gaba agonist

      • Recommended dose is 200-300mg per day. Slow uptitration watching out for side effects like weight loss, limb paresthesias and cognitive slowing.

  • Other potential treatments that are not yet ready for use:

    • Baclofen

    • Varenicline

    • Aripiprazole

    • Ondansetron

  • Pregnancy:

    • Aforementioned medications are not for use in pregnancy and should be avoided

    • Benzodiazepines may be used in acute withdrawal

 

References:

  1. Ries, R.K. & Fiellin, D.A. & Miller, S.C. & Saitz, R. (2014). The ASAM Principles of Addiction Medicine: Fifth edition.

  2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2945872/

  3. https://www.rethinkingdrinking.niaaa.nih.gov/

  4. Reus V, Fochtmann L, et al. The American Psychiatric Association Practice Guideline for the Pharmacological Treatment of Patients with Alcohol Use Disorder. Am J Psychiatry 2018; 175:86–90

  5. Center for Behavioral Health Statistics and Quality. (2017). 2016 National Survey on Drug Use and Health: Detailed Tables. Substance Abuse and Mental Health Services Administration, Rockville, MD. Retrieved from https://www. samhsa.gov/data/.

  6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3914416/

  7. O’Malley SS, Zween A, Fucito LM, et al. Effect of varenicline combined with medical management on alcohol use disorder with comorbid cigarette smoking: a randomized clinical trial. JAMA Psychiatry. 2018;75(2):129–138.

  8. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0203410

  9. Reus, V. I., Fochtmann, L. J., Bukstein, O., Eyler, A. E., Hilty, D. M., Horvitz-Lennon, M., … & McIntyre, J. (2018). The American Psychiatric Association Practice Guideline for the Pharmacological Treatment of Patients With Alcohol Use Disorder. American Journal of Psychiatry, 175(1), 86-90.

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