Treatment of Alcoholism and Addiction

Steven R. Ey, M.D.

Medical Director

Genesis Chemical Dependency Unit

South Coast Medical Center

Laguna Beach, CA

April 14, 2005

Addiction Reward Pathway

Admission Labs

Labs (BAL, CBC, Chem 22, Mg, TSH, RPR, lipase, UDS, UA, pregnancy test)

PPD CXR EKG Acetaminophen and salicilate level as

indicated

Absorption and Metabolism

Sites include stomach, small intestine, and colon Dependent on gastric emptying time Metabolized primarily in the liver by oxidation Alcohol dehydrogenase exhibits zero-order kinetics

(15 mg/dl/hr) Proportional to body weight Microsomal ethanol oxidizing system (MEOS) Alcohol inhibits cytochrome P-450

Alcohol Breakdown

Alcohol ADH

AcetaldehydeALDH

Acetic acid and water

Alcohol Intoxication

20-99mg% loss of muscular coordination, change in behavior

100-199mg% ataxia, mental impairment 200-299mg% obvious intoxication, nausea

and vomiting 300-399mg% severe dysarthria and amnesia

Alcohol Intoxication cont.

400-600mg% coma occurs 600-800mg% decreased respirations and

blood pressure, obtundation, often fatal Important to remember the role of tolerance

in all these categories

Management of Alcohol Intoxication

Cardiovascular and respiratory support to control blood pressure and maintain airway

Intravenous fluids (“Banana Bag-NS, thiamine, MVI, Folate, B-12)

Assess for other drug use especially benzo’s or opioids as antagonists can be used

Closely monitor until withdrawal begins and then start treatment

Monitoring Alcohol Withdrawal

MSSA (Modified Selective Severity Assessment)

CIWA-A (Clinical Institute Withdrawal Assessment for Alcohol)

Advantage for personnel to monitor progress and treat accordingly

Disadvantage is cookbook approach

Withdrawal Signs and Symptoms

Tremor Agitation Autonomic changes (BP, HR, Temp.) Seizures Sensorium changes (eg, hallucinations,

confusion)

Withdrawal Syndrome Stage 1

Begins within 24 hours Lasts up to 5 days 90% of cases do not go beyond stage 1 Other symptoms include depressed mood,

anxiety, diaphoresis, headache, nausea/vomiting, etc.

Withdrawal Syndrome Stage 2

Mostly untreated or undertreated in stage 1 Same signs and symptoms in stage 1 only

more severe Hallmark is hallucinations (generally

perceived as benign) Usually occurs 48 hours after last drink

Withdrawal Syndrome Stage 3

Usually occurs 72 hours after last drink Delirium Tremens (acute reversible organic

psychosis) has 2% mortality Lacks insight into hallucination, often

disoriented and labile Seen in persons with severe alcoholism

and/or significant medical problems

Detoxification Treatment

Begin benzodiazepine at onset of withdrawal symptoms

Be cautious that symptoms are withdrawal and not intoxication

If uncertain repeat BAC to be sure it is decreasing before sedating detoxification meds are instituted

Detox Pharmacology

Benzodiazepine and Barbiturate equivalents: Diazepam 10mg Lorazepam 2mg Phenobarbital 30mg Chlordiazepoxide 25mg Oxazepam 30mg

Detox Pharmacotherapy

Know 2-3 drugs well for routine detox (e.g., Diazepam 10-20 mg Q1 hr prn withdrawal)

Magnesium sulfate 2 gm for severe withdrawal (esp. in seizure risk)

Daily thiamine 100 mg, folate 1mg, and MVI Push fluids Supportive therapy (eg hypertension meds, etc.) Stage 3 withdrawal usually requires iv fluids, foley

catheter, soft restraints, etc.

Alcohol Withdrawal Seizures

More common in untreated alcoholics Should hospitalize if first seizure Need to be evaluated for other causes (eg, head injury,

CVA, or CNS infection, etc.) if first seizure or history not clear

Work up includes brain imaging and EEG 1 in 4 patients have a second seizure within 6-12 hours Must report any seizure to County Health Dept. and

inform patient not to drive

Alcohol Withdrawal Seizures

Mostly Grand mal seizures Usually 24-48 hours after last drink but may

be within 8 hours BAC does not have to be zero Less than 3% become status epilepticus Increased risk if prior seizure or detoxing off

sedative hypnotic as well

Substance Abuse, J Lowinson, MD. Third Edition, 1997, page 129.

GABA and NMDA Neuronal Receptors

Kindling and Seizures

Alcohol Withdrawal Seizure Treatment

Parenteral benzodiazepines (eg, ativan 2 mg or valium 10 mg iv stat)

Seizure precautions Valium 10-20 mg q1 hour prn or scheduled taper Anti-convulsants are generally not indicated unless

the diagnosis is in doubt Work up if 1st seizure Report to County Health Dept. and no driving until

cleared

Pharmacotherapy Treatment

Disulfiram Naltrexone Acamprosate

Disulfiram

Deterrent therapy Inhibits metabolism of alcohol by blocking

acetaldehyde dehydrogenase Acetaldehyde is toxic product causing the reaction

(flushed, tachycardia, diaphoresis, nausea, headache, etc.)

Metronidazole and alcohol may cause disulfiram like reaction

Disulfiram (cont.)

Prescribing tips (read the label for alcohol if not sure)

Monitor liver enzymes May cause psychosis Evaluate need for patient to take in front of

staff

Volpicelli, 1992

Naltrexone

Opiate blocker Evidence for reduced cravings and relapse

rates 23% relapsed vs. 54% placebo during 12

week study Definition of relapse

Krystal, et al. NEJM Volume 345, pg. 1734-39, Dec 13, 2001

Naltrexone cont.

VA study Dec 13, 2001 NEJM 627 veterans given 12 mo Naltrexone, or 3

mo. Naltrexone and 9 mo placebo, or 12 mo placebo

No statistically significant difference in # days to relapse at 13 weeks, and no difference in % days drinking at 52 weeks

Acamprosate

Affinity for GABA A and GABA B receptors

Inhibits glutamate effect on NMDA receptors

Now available in the United States

Acamprosate cont.

Multiple studies in Europe show it effectiveness and safety

Tempesta, et al. (2000) found abstinence rate 57.9% with acamprosate versus 45.2% with placebo

Sass, et al. (1996) found at the end of 48 weeks of treatment and 48 more weeks of follow-up that 39% of the acamprosate group vs. 17% of the placebo group remained abstinent

Case Scenario #1

40 y.o. male admitted with BAC 460 mg/dl. Communicates clearly History of recent Alcohol Withdrawal

Seizure History of multiple AMA’s during detox in

the past

Case Scenario #1 Treatment

Patient has high tolerance so medicate appropriately Monitor closely and repeat BAC to ensure it is

decreasing May use Librium 100 mg po or Phenobarbital 130

mg im to decrease risk of seizure Start valium 10-20 mg q 1 hour prn (or Ativan) Begin thiamine 100 mg, folate 1 mg, & MVI daily 2 gm MgSO4 if withdrawal difficult or Mg low Consider Depakote or Dilantin but not necessary

Case Scenario #2

55 y.o. female drinking 1 bottle wine per day and taking xanax 4 mg. per day

Smokes 1 pack per day cigarettes Complains of hip pain, fell 1 week ago

Case Scenario #2 Treatment

Alcohol detox with usual meds or Phenobarbital Slow klonopin taper as outpatient is one option but

there are more (eg anti-seizure meds and quick taper in hospital) to detox off of Xanax

Smoking cessation program Don’t forget to check the hip pain.

Case Scenario #3

30 y.o. female drinking 1-2 bottles of wine per day

History of Bulimia nervosa, last binge/purge 3 months ago

History of multiple relapses

Case Scenario #3 Treatment

Pregnancy test positive! OB/GYN consult but you can order an

ultrasound now Always treat as if they will keep the baby Detox med of choice is Phenobarbital Extended care in dual diagnosis program

Opioid Dependence

Physiologic dependence versus addiction Common opioids Rx drugs on the streets, etc. Abuse patterns

Opioid Withdrawal Signs

COWS Scale Elevated HR & BP, diaphoresis, restlessness,

pupil size, bone or joint aches, runny nose or tearing, GI upset, tremor, yawning, anxiety or irritability, gooseflesh skin

Score items stage to withdrawal

Opioid Treatment

Clonidine 0.1 mg every 2 hours prn Benzodiazepine or barbiturate prn (eg,

Phenobarbital 15-30 mg every 3 hours prn) NSAID Muscle relaxant (eg, methacarbamol) Bentyl for abdominal cramps Sleeping agent (eg, temazepam)

Opioid Treatment (cont.)

Subutex (buprenorphine) Suboxone (buprenorphine/naloxone) Sublingual administration of partial opioid

agonist Must be certified through DEA to use

Treatment with Suboxone

Certification requires ASAM, Addiction Psychiatry, or 8 hour training course

Capacity to provide or to refer patients for necessary ancillary services

Treat no more than 30 patients at one time

Opioid Case #1

45 y.o. female taking increasing doses of hydrocodone per day

Currently on 90 mg per day Repeatedly calling office, loses prescriptions No pain etiology to explain use of narcotics

Opioid Case #1 Treatment

Recommend inpatient detox in CD program Consider outpatient detox only in reliable,

motivated patient Clonidine 0.1 mg q 2 hrs. prn, NSAID,

Muscle relaxant, bentyl, benzo’s for anxiety and insomnia

Most CD programs using suboxone now

Sedative/Hypnotic Dependence

Difficult to detox Seizure prophylaxis important Rebound anxiety needs to be treated Methods to obtain meds include legitimate

prescriptions, prescription fraud, multiple MD’s or clinics, internet, foreign countries and the street

Sedative/Hypnotic Treatment

Taper as outpatient 10% of dose per week as outpatient

Quick taper as inpatient with anti-seizure meds

Consider valproic acid or other anti-seizure med for equivalent doses of valium 30 mg. per day or more (based on clinical experience)

Sedative/Hypnotic Case #1

32 yo male taking xanax for 3 years Began with xanax 0.5 mg. BID Now taking 6 mg. per day for 3 months Also on SSRI No history of seizure

Sed/Hyp Case #1 Treatment

Equivalent dose of valium 60 mg. per day Likely to have seizure if stops abruptly Recommend inpatient detox Start valproic acid 250 mg. QID, keep on therapeutic

dose minimum 6 weeks Substitute benzo or barb with limited doses for 5-7

days Consider zyprexa or equivalent Continue SSRI

Psychostimulants

Detox not a covered benefit Medical complications usually bring patient

to ER May admit for workup of Chest pain, CVA,

seizure, etc. Referral to program

Nicotine

Fagerstrom Test Nicotine Replacement (gum, patches) Bupropion Support Groups