1. 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

2. Addiction Reward Pathway

3. Admission Labs
Labs (BAL, CBC, Chem 22, Mg, TSH, RPR, lipase, UDS, UA, pregnancy test)
PPD
CXR
EKG
Acetaminophen and salicilate level as indicated

4. 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

5. Alcohol Breakdown
Alcohol ADH Acetaldehyde ALDH Acetic acid and water

6. Alcohol Intoxication
20-99mg% loss of muscular coordination, change in behavior
mg% ataxia, mental impairment
mg% obvious intoxication, nausea and vomiting
mg% severe dysarthria and amnesia

7. Alcohol Intoxication cont.
mg% coma occurs
mg% decreased respirations and blood pressure, obtundation, often fatal
Important to remember the role of tolerance in all these categories

8. 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

9. 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

10. Withdrawal Signs and Symptoms
Tremor
Agitation
Autonomic changes (BP, HR, Temp.)
Seizures
Sensorium changes (eg, hallucinations, confusion)

11. 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.

12. 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

13. 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

14. 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

15. Detox Pharmacology Benzodiazepine and Barbiturate equivalents:
Diazepam 10mg
Lorazepam 2mg
Phenobarbital 30mg
Chlordiazepoxide 25mg
Oxazepam 30mg

16. Detox Pharmacotherapy
Know 2-3 drugs well for routine detox (e.g., Diazepam 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.

17. 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

18. Alcohol Withdrawal Seizures
Mostly Grand mal seizures
Usually 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

19. GABA and NMDA Neuronal Receptors
Substance Abuse, J Lowinson, MD. Third Edition, 1997, page 129.

20. Kindling and Seizures

21. Alcohol Withdrawal Seizure Treatment
Parenteral benzodiazepines (eg, ativan 2 mg or valium 10 mg iv stat)
Seizure precautions
Valium 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

22. Pharmacotherapy Treatment
Disulfiram
Naltrexone
Acamprosate

23. 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

24. 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

25. Naltrexone Opiate blocker
Evidence for reduced cravings and relapse rates
23% relapsed vs. 54% placebo during 12 week study
Definition of relapse
Volpicelli, 1992

26. 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
Krystal, et al. NEJM Volume 345, pg , Dec 13, 2001

27. Acamprosate Affinity for GABA A and GABA B receptors
Inhibits glutamate effect on NMDA receptors
Now available in the United States

28. 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

29. 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

30. 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 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

31. 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

32. 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.

33. 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

34. 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

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

36. 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

37. Opioid Treatment Clonidine 0.1 mg every 2 hours prn
Benzodiazepine or barbiturate prn (eg, Phenobarbital mg every 3 hours prn)
NSAID
Muscle relaxant (eg, methacarbamol)
Bentyl for abdominal cramps
Sleeping agent (eg, temazepam)

38. Opioid Treatment (cont.)
Subutex (buprenorphine)
Suboxone (buprenorphine/naloxone)
Sublingual administration of partial opioid agonist
Must be certified through DEA to use

39. 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

40. 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

41. 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

42. 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

43. 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)

44. 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

45. 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

46. 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

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