1. Alcohol Use Disorder Assessment & Treatment Strategies
Sharon Vipler
MD, CCFP, dipl.ABAM

2. No financial or commercial conflicts of interest and
St. Pauls’ Hospital Addiction Medicine Consult Team
Medical Lead, Creekside Withdrawal Management Centre (Inpatient unit and RAAC)
Surrey Memorial Hospital Addiction Medicine Consult Liaison team
Quibble Creek Opioid Agonist Therapy Clinic
BCCSU Clinical Expert
Disclosures
No financial or commercial conflicts of interest and
no identified mitigating biases.

3. Objectives Diagnosis of Alcohol Withdrawal
Understand the neurobiology of acute alcohol withdrawal and develop an approach to the management of acute withdrawal
Explore the pharmacological options for relapse prevention

4. But first…

5. What’s being used?

6. Who’s using Alcohol

12. Alcohol and the Brain Alcohol is a central nervous system depressant
It simultaneously enhances inhibitory tone (via GABA) and inhibits excitatory tone (via glutamate)
Constant presence of ethanol = new homeostasis
Abrupt cessation =
Reveals adaptive responses to chronic ethanol use
Results in over activity of central nervous system
UpToDate
Management of Moderate and Severe Alcohol Withdrawal Syndromes -- UpToDate

13. GABA (gamma aminobutyric acid)
Major inhibitory neurotransmitter in the brain
Highly specific binding sites for ethanol on GABA receptor complex.
Constant etoh = insensitivity to GABA = more inhibitor required to maintain constant inhibitory tone
As etoh tolerance develops – Arousal is maintained at alcohol concentrations normally producing lethargy in relatively alcohol naïve patients.
Cessation (or reduction) of alcohol = decreased inhibitory tone.
UpToDate

14. Excitatory Amino Acids (Glutamate)
Glutamate is one of the major excitatory amino acids. Binds to NMDA receptor = calcium influx, leading to neuronal excitation. Ethanol inhibits glutamate induced excitation. Adaptation occurs by increasing number of glutamate receptors in an attempt to maintain a normal state of arousal. Cessation (reduction) of alcohol results in unregulated excess excitation.
UpToDate Management of moderate and severe alcohol withdrawal syndromes

15. Acute Withdrawal

16. Minor Withdrawal Symptoms
Insomnia
Tremulousness
Mild anxiety
Gastrointestinal upset; anorexia
Headache
Diaphoresis
Palpitations
Symptoms usually present within 6 hours of cessation of drinking.
Can develop while patient still has a significant blood alcohol concentration
If no further progression of withdrawal, symptoms can resolve within 24 to 48 hours
uptodate

17. Withdrawal Seizures Generalized tonic clonic convulsions
Usually singular or a brief flurry of seizures over a short period
Usually occur within hours after the last drink
uptodate

18. Alcoholic Hallucinosis
NOT synonymous with delirium tremens
Usually visual hallucinations
Auditory and tactile hallucinations may also occur
No associated global clouding of sensorium and vital signs usually normal
Develop within hours of abstinence
Typically resolve within hours (earliest development of DTs is around the 24 hour mark)
uptodate

19. Delirium Tremens (DTs)
Synonymous to severe alcohol withdrawal in most texts
Hallucinations, disorientation, tachycardia, hypertension, hyperthermia, agitation and diaphoresis, in the setting of acute reduction or abstinence from alcohol.
Symptoms typically persist up to 7 days (in absence of complications)
Approximately 5-10% of patients in alcohol withdrawal develop DTs.
Associated with a mortality rate of up to 5 percent.
Previously (early 20th century) mortality rate approached 40%. Improvement likely result of earlier diagnosis, improvements in supportive and pharmacological therapies and improved management of comorbid illness.

20. “Kindling” Effect in Alcohol Withdrawal
The term “kindling” was first introduced by Goddard et al (1969) to explain a phenomenon noted after repeated weak electrical stimulation of the brain. Initial stimulation resulted in no seizure activity.
After repeated periodic application, the same stimulus induced full motor seizures. The brain had become sensitized to the stimulation.
Later, it was shown that sensitization could occur in the setting of electrical or chemical stimulation.
Goddard et al. A permanent change in brain function resulting from daily electrical stimulation. Experimental Neurology 25: , 1969.
Goddard et al. A permanent change in brain function resulting from daily electrical stimulation. Experimental Neurology 25: , 1969.

21. Kindling
For kindling to occur, the stimulus needs to be administered in a repeated and intermittent fashion.
Researchers have postulated that each withdrawal-induced episode of CNS hyperexcitability may serve as a stimulus that supports a kindling process.
Kindling in Alcohol Withdrawal
Alcohol Health and Research World Vol 22, No.1, 1998
Howard Becker
Kindling in Alcohol Withdrawal, Becker. Alcohol Health and Research World Vol 22, No.1, 1998.

22. Acute Withdrawal
….management

23. CIWA-Ar Most widely used clinical tool for management of AWS
Based on patient report and observer rating
Validated only in mild-to-moderate WD
Does not incorporate vital sign assessment (can be important in recognizing severe AWS)
Not a prediction tool – tool to recognize severity of withdrawal as it is occurring.
Maldonado et al (2014),
Maldonado et al (2014)

24. CIWA-Ar
Additionally, initiating CIWA in certain patient populations is not without risk….
Care needs to be taken when initiating CIWA protocols
Ensure that alcohol withdrawal is truly the cause of the patient’s presentation
Providing benzodiazepines to a patient who has evolving delirium for reasons other than alcohol withdrawal is very risky and can create situations exceedingly difficult to manage.

25. Management of Alcohol Withdrawal:
Barbiturates
Benzodiazepines
Fixed dosing vs symptom triggered dosing

26. pharmacological options
Relapse prevention
pharmacological options

27. Disulfiram FDA approved 1951 Aversive agent
Blocks aldehyde dehydrogenase = build up of acetylaldehyde
Flushing, tachy, sob, N/V, HA, etc
Serious potential SE
Low adherence
Possible utility in highly motivated, specific situations

28. Naltrexone FDA approved 1994 Opioid antagonist
less pleasure derived from drinking
Reduces relapse to heavy drinking (NNT = 11)
Target dose = 50mg OD (titrate up to target dose)
Avoid in patients with depression or hepatic dysfunction or opioid req’ment.
HA/dizziness (12%) and nausea (14%) most common SE
ACP Journal Club; 10/1/2014, Vol. 161 Issue 8, p6-6

29. Acamprosate FDA approved 2004
Inhibitor of glutamate and modulator of GABA (“gaba- ergic”)
Reduces chronic withdrawal symptoms
Can help maintain abstinence (NNT = 11)
Dose 666mg TID (333mg TID in moderate renal impairment)
avoid in severe renal impairment
Diarrhea/other GI (17%) most common SE
ACP Journal Club Rösner S, et al

30. Gabapentin Off label use Another “gaba-ergic” agent
Unique in that can be initiated during acute withdrawal (acts as bzd sparing agent)
Can be continued for relapse prevention
Improves rates of abstinence and no heavy drinking days (NNT 8)
Target dose 600mg tid

31. Other considerations

34. If the patient be in the prime of life and from drinking he has trembling hands, it may be well to announce beforehand either delirium or convulsion
--Hippocrates