Management of Alcohol Use Disorder

1. ALCOHOLISM: MANAGEMENT
Soumen Karmakar

2. Unit of Alcohol(1)
• 1 unit = 10 ml of Ethanol
E.g. 250 ml wine with 10% alcohol = 2.5 units
• Weekly limits in units (NICE)

3. Reducing Harmful Drinking
• FRAMES (NICE recommendation)
Feedback
Responsibility
Advice
Menu
Empathy
Self-efficacy

4. Assessing Alcohol Use
Detailed History:
• H/O: alcohol use- daily consumption, recent patterns, most recent drink
• Severity of dependence & withdrawal symptoms
• H/O: other drug use
• P/H/O: withdrawal symptoms
• Co-existing medical & psychiatric problems
• Physical examination
• Assessment of cognitive function
• Lab: CBC, LFT, RFT, Electrolytes, PT, INR, Urinary drug screen

5. Structured Assessment Tools: AUDIT
• Alcohol Use Disorders Identification Test
• 10 item questionnaire
• Q 1-3: quantity of alcohol consumed
• Q 4-6: signs & symptoms of dependence
• Q 7-10: behaviors & symptoms a/w harmful alcohol use
• Each Q scored 0-4, Max score 40
• Score ≥8 s/o hazardous/harmful use

7. Structured Assessment Tools: SADQ
• Severity of Alcohol Dependence Questionnaire
• 20 item questionnaire
• Each item score 0-3, Max score 60
• Severity of Alcohol Dependence
Mild: ≤15
Moderate: 15-30
Severe: ≥30

8. Alcohol Withdrawal (1)
• In dependent, neuroadaptation to presence of alcohol
• Blood Alcohol Concentration (BAC) is lowered, brain remains in hyperexcited
state, resulting in withdrawal
• Self-limiting symptoms: tremor, sweating, n/v, retching, tachycardia, agitation,
headache, insomnia, malaise
• In moderate to severe dependence: withdrawal may be a/w seizures, Wernicke’s
encephalopathy, DT

9. Features of Alcohol Withdrawal (1)

10. Alcohol Detoxification (1)
• Pharmacologically assisted withdrawal
• Likely to be needed when
Regular consumption > 15 units/day
AUDIT score > 20

11. Withdrawal Assessment (1)
• Symptom scales – helpful in determining adequacy of prescribed regimen
CIWA-Ar: Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised
10 item Objective scale
SAWS: Short Alcohol Withdrawal Scale
10 item self complete tool
• CIWA-Ar > 15 or SAWS > 12 : Assisted withdrawal

12. CIWA-Ar

13. Setting for Detoxification: Outpatient (1)
• Generally community/outpatient.
• Ideally 24 hours monitoring at home.
• Medication to be picked up daily/alternate day basis.
• Patient to be seen regularly during process.
• Should include psychosocial support, such as motivational interviewing.
• Assisted withdrawal should stop if patient resumes drinking.

14. Setting for Detoxification: Inpatient (1)
• Likely to be required if:

15. Drugs for Detoxification (1)
• Benzodiazepines are the TOC for alcohol withdrawal.
• Exhibit cross tolerance with Alcohol and have anticonvulsant properties
• Use supported by: NICE guidelines, Cochrane systematic reviews & BAP
guidelines.
• Chlordiazepoxide is most commonly used; considered to have relatively low
dependence-forming potential.
• Some centre use Diazepam.
• In hepatic impairment, Oxazepam or Lorazepam is TOC.
• Parenteral Thiamine & other vitamin replacement is an important adjunctive
treatment.

16. Assisted Withdrawal regimens (1)
• Fixed dose reduction: most commonly used
• Variable dose reduction: less benzodiazepine used, but reserved for setting
where staffs have specialist training
• Front-loading: infrequently used.
• Assisted withdrawal never to be started if BAC is very high or still rising.

17. Fixed Dose Reduction regimen (1)
• Used in community or non-specialist inpatient settings.
• Dose of benzodiazepine selected after assessment of severity of dependence
(clinical history, number of units per drinking day and SADQ score)
• For Chlordiazepoxide: rule of thumb is that the starting dose estimated from
current alcohol consumption
• Eg: 20 units/day = starting dose 20 mg QDS and tapered to zero over 5-10 days.
• Withdrawal symptoms to be monitored using CIWA-Ar or SAWS

18. Dosing with Level of Dependence (1)
• Mild: very small doses or no Chlordiazepoxide at all
• Moderate: 10-20mg Chlordiazepoxide QDS, reducing over 5-7days

19. Dosing with Level of Dependence (1)
• Severe: Intensive daily monitoring in first 2-3 days. Dose tapered over 7-10 days
or even longer.

20. Variable Dose Reduction/Symptom-triggered regimen (1)
• Used in specialist inpatient settings & in patients with no H/O complications
• Regular monitoring of pulse, BP, temperature, level of consciousness, severity of
withdrawal symptoms (CIWA-Ar/SAWS)
• Medication is given only when withdrawal symptoms are observed.
• Typical example: 20-30 mg Chlordiazepoxide hourly as needed
• Generally last for 24-48 hours, then switched over to fixed dosing schedule.

21. Front-loading Regimen (1)
• Initial loading dose of chlordiazepoxide 100mg
• Followed by 50-100mg 4-6 hourly, until light sedation achieved
• Patient monitored every 2 hours
• C/I in advanced liver disease, COPD, head injury

22. Considerations (1)
• CIWA-Ar > 15 or SAWS > 12 suggests the regimen prescribed is inadequate &
further intervention necessary
• Hallucinations/Agitation: increased dose of benzodiazepines required
• Hepatic impairment: Oxazepam
• Chronic respiratory disease: Oxazepam
• Chlordiazepoxide & Oxazepam have nearly similar potencies

23. Complications A/W withdrawal
• Seizures
• Hallucinations
• DT
• Wernicke’s Encephalopathy

24. Seizures (1)
• First time seizure during assisted withdrawal: R/O organicity or idiopathic
epilepsy
• Longer acting benzodiazepines (eg Diazepam) recommended for medically
assisted withdrawal with P/H/O seizures
• Carbamazepine loading recommended: untreated epilepsy, more than 2 seizures
during previous withdrawal episodes or previous seizure despite adequate
benzodiazepine loading
• No role of Phenytoin
• For alcohol withdrawal seizure: no need to continue anticonvulsants long term

25. Hallucinations (1)
• Mild cases respond to chlordiazepoxide
• Resistant cases: Oral haloperidol used
• Haloperidol can be given IM or IV also

26. Delirium Tremens (1)
• Toxic confusional state when withdrawal symptoms severe
• Risk factors: long H/O dependence, severe dependence, multiple previous
withdrawals, old age, H/O DT or alcohol related seizures, other medical disorder
• Classic Triad: clouding of consciousness/confusion, vivid hallucinations, tremors
• Other C/F: paranoid delusions, agitation, insomnia, autonomic hyperactivity
• Symptoms peak between 72-96 hours after last drink
• Prodromal: Night time insomnia, restlessness, fear, confusion
• Treatment: early diagnosis, prompt transfer to specialist setting, IV diazepam,
fluid & electrolyte replacement, IV thiamine

27. Wernicke’s Encephalopathy (1)
• Progressive neurological condition caused by Thiamine deficiency
• Malnourished secondary to restricted diet/Reduced absorption of Thiamine
• Thiamine required to utilize glucose. Glucose load in thiamine-deficiency can
precipitate Wernicke’s encephalopathy
• Classical symptoms triad: ophthalmoplegia, ataxia, global confusion – Rare
• Presumptive diagnosis (During detoxification): ataxia, hypothermia,
hypotension, confusion, ophthalmoplegia, nystagmus, memory disturbance,
unconsciousness/coma.
• Treatment: transfer to specialist facility, IV thiamine
• Left untreated: progress to Korsakoff’s psychosis (permanent memory
impairment, confabulation, confusion, personality changes)

28. Thiamine recommendations (NICE) (1)
• Parenteral B-complex must be administered before glucose in all patients with
altered mental status.
• Community detoxification: oral thiamine
• All Inpatient detoxification: IM thiamine 500 mg daily x 5 days, followed by oral
thiamine/B-complex as long as needed
• Suspected/ established Wernicke’s encephalopathy: IV thiamine 1000 mg TDS x 3-
5 days, followed by 500 mg daily x 3-5 days or longer

29. (1)

30. (1)

31. Relapse Prevention
• No role of benzodiazepines beyond treatment of acute withdrawal symptoms
• Acamprosate & Disulfiram licensed in UK(1)
• Acamprosate, Naltrexone, Disulfiram USFDA approved (2)
• Pharmacotherapy in combination with psychosocial treatment

32. Acamprosate (1)
• Synthetic taurine analogue
• Functional glutamatergic NMDA antagonist. Also increases GABA-ergic function
• NNT for abstinence 9-11. Treatment most pronounced at 6 months, significant
upto 12 months
• BAP guidelines: should be started during detoxification for potential
neuroprotective effect.
• Well tolerated drug. Lack of hepatic metabolism. Excreted though Kidney(2)
• S/E: diarrhoea, abdominal pain, N/V, pruritus
• C/I: severe renal impairment (CrCl <30ml/min(2)), pregnancy, lactation

34. Naltrexone (1)
• Non-selective opioid receptor antagonist (μ>δ>κ)
• Prevents increased dopaminergic activity after consumption of alcohol, reduces
rewarding effects. Significantly reduces relapse. Reduces Craving. (2)
• Usual dose 50 mg/day. Recent US trials 100mg/day
• Well tolerated. S/E: nausea, headache, abdominal pain, anorexia, fatigue.
• Baseline LFT, RFT. C/I: acute liver failure
• Can be started when patients are still drinking or during assisted withdrawal
• Opioid analgesics if required, used after 48-72 hours of naltrexone cessation
• Injectable preparations developed for improving compliance. Dose 380mg
4weekly IM(2)

36. Disulfiram (Antabuse) (1)
• 2nd line option for moderate to severe dependence (NICE)
• Inhibits aldehyde dehydrogenase, leading to aldehyde accumulation after drinking,
causing unpleasant physical effects. Continued drinking may lead to arrythmias,
hypotension & collapse
• Ensure no alcohol consumed for atleast 24 hours before commencing treatment.
• S/E: common- halitosis. Rare- hepatoxicity
• C/I: heart failure, CAD, HTN, h/o CVD, pregnancy, breastfeeding, liver disease,
peripheral neuropathy & severe mental illness.
• Baseline LFT, RFT, electrolytes
• Dose: 800 mg first dose, reducing to 100-200 mg daily for maintenance.
• Comorbid alcohol & cocaine dependence: 500 mg daily.

38. Nalmefene (1)
• Opioid antagonist
• Reduces heavy drinking days
• Do not promote abstinence
• Limited role in relapse prevention

39. Baclofen (1)
• GABA-β agonist
• May have role in reducing anxiety in severely dependent patients
• Well tolerated, can be given to dependent patients with cirrhosis
• 10-20mg TDS

40. Anticonvulsants (1)
Topiramate
• Reduce the percentage of heavy drinking days
• Improve harmful consequences of drinking, physical health and QoL
• Dose: 25 mg daily, increase to 300 mg daily
• S/E: parasthesia, dizziness, altered taste, anorexia, weight loss, difficulty in memory
and concentration
• Less common but notable side effects include metabolic acidosis, nephrolithiasis, and
precipitation of acute angle-closure glaucoma.(2)
Pregabalin & Gabapentin
• Limited but promising evidence of efficacy in withdrawal and in reducing drinking.

41. Special Populations

42. Pregnancy & Alcohol Use (1)
• Complete abstinence advised
• If not possible, abstinence for first 3 months, consumption limited to 1-2 units
once/twice a week for the rest of pregnancy
• Dependant woman with withdrawal symptoms-pharmacological cover for
detoxification offered in inpatient setting
• Chlordiazepoxide suggested to be used, but dose dependent malformations have
been observed.
• No relapse prevention medications(2)

43. Extremes of age (1)
• Children & Adolescents: lower dosage of chlordiazepoxide used.
• Older adults: lower dosage of benzodiazepines, shorter acting drugs may be
preferred.

44. Concurrent Alcohol and Other Drug Use Disorders (1)
• Benzodiazepine co-dependence: best managed with single long acting
benzodiazepine. Starting dose (equivalent dose) should take into account typical
daily dose of both alcohol and relevant benzodiazepine. Inpatient treatment
carried out over 2-3 weeks period or longer.
• Cocaine co-dependence : daily dose of 500 mg disulfiram or 150 mg naltrexone
have been used.
• Opioid co-dependence : both to be treated. Naltrexone used.
• Nicotine co-dependence : encourage to quit smoking. In inpatients-nicotine
patches/inhalator may be used during assisted alcohol withdrawal

45. Co-morbid mental health disorders (1)
• Anxiety & depression common
• For most people, symptoms diminish after 3-4 weeks of abstinence.
• RDD, BPAD, Anxiety disorder, OCD, PTSD may be initial trigger to drinking
• Specialist centres offering psychological as well as pharmacological treatments
required

46. Depression (1)
• TCAs have better performance than SSRIs but have more S/Es
• Greater antidepressant effect if diagnosis made one week after abstinence,
excluding affective symptoms d/t withdrawal
• Escitalopram & Mirtazapine tried with promising results
• Relapse prevention medication used concurrently.
• Sertraline 200 mg with naltrexone 100mg daily has good outcomes.
• Acamprosate can also ne used

47. Bipolar Affective Disorder (1)
• Valproate and lithium combination a/w better drinking outcomes, but no extra
benefit on mood than lithium alone
• Lithium avoided in binge drinkers d/t chance of electrolyte imbalance and
toxicity
• Concurrent relapse prevention strategies. Naltrexone tried first, the acamprosate
and lastly disulfiram

48. Anxiety (1)
• Common during intoxication, withdrawal as well as abstinence
• Difficult to diagnose as separate entity
• Assisted withdrawal and supported abstinence for upto 8 weeks required before
full assessment.
• Role of benzodiazepines controversial d/t chance of abuse & dependence
• Buspirone, paroxetine & baclofen have been tried with success
• Abstinence & relapse prevention to be ensured

49. Schizophrenia (1)
• Naltrexone or acamprosate may be considered
• Antipsychotic medications to be optimized
• Clozapine may be considered

53. • In choosing between acamprosate and naltrexone for an individual patient,
selection of a medication is likely to be guided by factors such as ease of
administration, available formulations, side effect profile, potential risks in
women who are pregnant or breastfeeding, the presence of co-occurring
conditions (e.g., hepatic or renal disease), or the presence of specific features of
AUD (e.g., craving).
• Decisions about the duration of treatment with these medications will also be
based on individual factors such as patient preference, disorder severity, history
of relapses, potential consequences of relapse, clinical response, and tolerability.
• There is insufficient evidence available on concomitant use of acamprosate and
naltrexone to determine the benefits and harms of combined treatment or to
make any statement about using these medications together.

55. • Abstain from drinking alcohol for at least 12 hours before taking a dose of the
medication and be advised that reactions with alcohol can occur up to 14 days
after taking disulfiram
• Well tolerated at dose of 250 mg daily
• Not advised in patients with seizure disorder
• Assessment of cardiac function to be assessed before starting

57. • Topiramate was associated with significant reductions in the percent of heavy
drinking days and the percent of drinking days in most, but not all studies. Also
showed improvements in other drinking outcomes, such as drinks per drinking
day and abstinence, the subjective experience of “craving”, and quality of life and
well-being.
• Topiramate was typically administered at doses of 200–300 mg daily, but gradual
dose titration may minimize some of the medication’s adverse effects.
• Gabapentin, at doses between 900 and 1800 mg/day, was associated with an
increased rate of abstinence (number needed to treat [NNT]=8 for 1800 mg daily)
and a reduction in heavy drinking days (NNT=5 for 1800 mg daily. Reductions
were also noted in drinking quantity and frequency, GGT, craving, mood, and
insomnia.

58. Other medications(2)
• Other medications are being investigated for use in the treatment of AUD.
Examples include zonisamide and ondansetron.
• Alcohol-related outcomes were also reduced by varenicline in several studies,
suggesting that varenicline may be a promising treatment of AUD, particularly
for individuals with co-occurring nicotine dependence.
• Aripiprazole treatment was associated with reduced secondary endpoints of
harm and reduced drinking However, aripiprazole could be considered in a
patient with AUD and another indication for this medication.
• Findings with baclofen are mixed, and recent RCTs have found no benefit of its
use in treatment for AUD.
• Nalmefene has also been studied in AUD in multiple European trials but is not
available in the United States or Canada

61. References
1. The Maudsley Prescribing Guidelines in Psychiatry, 12th Edition, 2015
2. Practice Guideline for the Pharmacological Treatment of Patients With Alcohol
Use Disorder, APA, 2017