Pharmacologic Treatment Options for Alcohol Dependency

Damon Landreau, D.O.LCDR/USPH/USCG Flight Surgeon

Objectives

• Review basic neurobiology• Review “road ahead” views of Alcohol

Dependency• Review treatment options• Look at a few Coast Guard Pictures

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

Understanding this process is the key to understanding dependency

Implications

The process for neurotransmission is highlyregulated on the molecular level.

1. Dysregulation is the core molecular problem of dependency

2. Symptoms of dysregulation may be overcome with treatment.

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

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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• Provide Healthcare to active duty and reserve personnel to support USCG missions

• Maintain medical and dental readiness for world wide deployment

• Oversight of occupational and preventative services

USCG Clinics

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Drugs Effects - Molecular LevelDrug Effects

Nicotine Acetylcholine

Amphetamine , Cocaine Dopamine

Marijuana Endocannabinoids

Opiates Endorphins

Benzo’s Gamma-aminobutyric Acid (GABA)

LSD Serotonin

Note – very specific actionsThe Neurobiology of Addiction, Erickson, C.K. , 2009 pg 33

AlcoholNeurotransmitter system Effects of alcohol

Gamma-aminobutyric acid (GABA) Enhance

Glycine Enhance

Acetylcholine Enhance

Serotonin Enhance

Adenosine triphosphate (ATP) Inhibit

Glutamate Inhibit

Voltage-gated (several) Enhance + inhibit

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

Genetic PredispositionDrugs % Dependency Over Time

Nicotine 32%

Heroine 23%

Crack 20%

Cocaine 17%

ETOH 15%

Stimulants 11%

Opiates 9%

Sedatives 9%

Marijuana 9%

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

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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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Medications

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

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

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

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

Naltrexone

• Contraindications– Opioid Use – consider drug testing– Acute Hepatitis– Acute liver failure

• Side Effects– Nausea, headache, dizziness – most common

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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

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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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

Topiramate (Topamax)

• Increases GABA and decreases glutamate function (opposite of ETOH)

• Reduces # of heavy drinking days• Increased # abstinent days• Not FDA approved

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

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Center

Varenicline (Chantix)

• Antagonizes nicotinic acetylcholine receptors• May reduce the rewarding properties and

cravings • Not FDA approved

SSRI

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

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

Questions?