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 Acetaldehyde ALDH 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

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

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

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

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. 1734-39, Dec 13, 2001

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