Pharmacologic Treatment Options for Alcohol Dependency

1. Pharmacologic Treatment Options for Alcohol Dependency Damon Landreau, D.O. LCDR/USPH/USCG Flight Surgeon

2. Objectives • Review basic neurobiology • Review “road ahead” views of Alcohol Dependency • Review treatment options • Look at a few Coast Guard Pictures

3. Neurobiology 101 • Neurons are the functional unit of the nervous system • They release neurotransmitters(NT) via electrical impulses – we currently know of about 60 • Neurotransmission occurs in 3 basic stages • Sending neuron releases NT via electrical impulses via flow of Na and K • Receiving neuron binds the NT at a receptor • Chemical changes happen that are similar to the process of the sending neuron

4. Understanding this process is the key to understanding dependency

5. Implications The process for neurotransmission is highly regulated on the molecular level. 1. Dysregulation is the core molecular problem of dependency 2. Symptoms of dysregulation may be overcome with treatment.

6. Mesolimbic Dopamine System (MDS) • Primal emotional center of the brain • Components • Anterior cingulated cortex – autonomic nervous system, cognition, decision making • Ventral tegmental area – primary site of drug actions • Nucleus accumbens - pleasure center • Frontal/prefrontal cortex – executive functions • Amygdala – emotional center

8. Drug Dysregulation • Down/Up regulates production of NT • Depletes NT stores • Blocks release of NT • Inhibits NT transport systems • Binds to receptors blocking NT • Blocks the second messenger - electrical and chemical impulses caused by NT

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10. USCG Clinics

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12. Drugs Effects - Molecular Level Note – very specific actions The Neurobiology of Addiction, Erickson, C.K. , 2009 pg 33

13. Alcohol Principles of addiction medicine, 3d ed, 2003, page 104 [ISBN = 1-880425-08-4]. Compliments of Dr David Franz

14. Genetic Predisposition The Neurobiology of Addiction, Erickson, C.K. , 2009 pg 47

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16. Road Ahead • Approaching Dependency as a Chronic Disease • Expect relapse • Success greatly depends on behavioral changes • Medications may help • Disease Management Systems • Exploring Medications as more Neurobiology is understood • More research and doing away with the untreatable stigmata

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18. Medications • Will not cover alcohol detox • FDA and non-FDA options • Much is expert opinion

20. Clev Clin J Med 2006;73:641 [PMID = 16845975]. Compliments of Dr David Franz

21. Naltrexone • Opioid Antagonist • Decreases the acute pleasure of drinking by blocking endogenous opioids that reinforce the pleasure • Reduces relapse frequency in ~ 50% of alcoholics • More effective when there is a strong Family History of ETOH

22. Naltrexone • Dosage • Oral 50-100 mg/day for 12 weeks • Some advocate 6-12 months of treatment • Depot naltrexone – 380 mg IM (gluts) q 4 weeks. • Monitor for local injection site complications • FDA approved

23. Naltrexone • Contraindications • Opioid Use – consider drug testing • Acute Hepatitis • Acute liver failure • Side Effects • Nausea, headache, dizziness – most common

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25. Acamprosate (Campral) • Exact mechanism is unknown, but it targets the glutamate system • May helps in decreasing the amount of ETOH used • Renal clearance – consider with liver disease • FDA approved

26. Disulfiram (Antabuse) • Increases amount of acetaldehyde after ETOH • Causes a noxious reaction • Not very effective – it has shown to decrease the amount ETOH but not abstinence • FDA approved

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28. Ondansetron (Zofran) • Affects the corticomesolimbic dopamine pathway and effects the reward pathways that are activated by alcohol • Most effective for early onset alcohol dependence. • Not FDA approved

29. Topiramate (Topamax) • Increases GABA and decreases glutamate function (opposite of ETOH) • Reduces # of heavy drinking days • Increased # abstinent days • Not FDA approved

30. Baclofen • Alcohol alters the balance between gamma-aminobutyric acid (GABA) and glutamate • Baclofen increases GABA function • May reduces alcohol cravings and leads to a higher rate of abstinence • Not FDA Approved

31. National Maritime Center

32. Varenicline (Chantix) • Antagonizes nicotinic acetylcholine receptors • May reduce the rewarding properties and cravings • Not FDA approved

33. SSRI • May be more effective when: • Co-Morbid depression • Older age with onset of ETOH • Not a strong family history

34. Pharmacologic Strategies to Reduce Drinking Behavior • Reduce ETOH seeking and craving • Naltrexone, ondansetron, topiramate • Reduce dysphoria and sxs of acute and protracted withdrawal • Acamprosate, sedatives, baclofen, anti-epileptics • Reduce ETOH bioavailability • Kudzu, alpha 2 antag (clonidine) • Reduce impulsivity/attention deficits • Dopamine agonist and antagonist, ondansetron • Treat comorbid psychiatric disease • TCA, SSRI, antipsychotics, buspirone Adapted from Pharmacologic Interventions for the Treatment of Addiction – Dr. Marvin Seppala

35. Questions?