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Guidance on the Treatment of Alcohol and Benzodiazepine Dependence in Adults

for Inpatient Units - version 1.1

Incorporating

Guidance on the Management of Alcohol Withdrawal and the Prevention of Wernicke-Korsakoff Syndrome

RATIFYING COMMITTEE Drugs and Therapeutics Group

DATE RATIFIED 24.04.17 with a minor amendment to the We3rnicke's prevention advice - January 2020

NEXT REVIEW DATE April 2020

AUTHORS Dr James Fallon - Consultant Psychiatrist Helen Manuell – Clinical Pharmacist Originally written by Dr Hugh Williams - Consultant Psychiatrist, Hon. Clinical Senior Lecturer (no longer working for the Trust)

Summary:

This guidance aims to assist inpatient staff in the safe and appropriate prescribing and administration of medicines for adults undergoing treatment for alcohol problems This document is compliant with the NICE clinical guidelines 100 and 115 on alcohol dependence and alcohol-use disorders.

If you require this document in another format, ie easy read, large text, audio, Braille or a community

language please contact the Pharmacy Team on 01243 623349 (Text Relay calls welcome)

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CONTENTS Page 1. Management of Alcohol Withdrawal and the Prevention of Wernicke / Korsakoff syndrome. 1.1 Alcohol Withdrawal Syndrome 3 1.2 Pharmacological management of alcohol detoxification 3 1.3 Prevention of Wernicke Korsakoff syndrome 5 1.4 General management 6 2. Pharmacological Management used in Relapse Prevention in alcohol dependence 2.1 Prescribing advice for acamprosate 6 3. Benzodiazepine withdrawal 3.1 Benzodiazepine stabilisation 7 3.2 Doses of benzodiazepines equivalent to 5mg diazepam 8 3.3 Benzodiazepine detoxification 8 4. References 9

Appendices 10

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1. Management of Alcohol Withdrawal and the Prevention of Wernicke / Korsakoff syndrome. 1.1 Alcohol Withdrawal Syndrome Not all heavy drinkers will experience withdrawal phenomena and there is a wide range in the severity of withdrawal symptoms. In some cases withdrawal may be life threatening. It is therefore important to recognise early clinical features and treat them appropriately. Early withdrawal symptoms occur up to 12 hours after the last drink. They include tremor, sweating, anorexia, nausea, insomnia and anxiety. In moderate withdrawal the signs are more marked and transient auditory hallucinations in clear consciousness may also occur. Withdrawal fits (“rum fits”) can occur at 12 to 48 hours and are more likely if there is a previous history of withdrawal fits or epilepsy. Fits tend to be generalised tonic-clonic (if focal, suspect other causes e.g.head injury) and may occur in bouts. In 30% of cases, fits are followed by delirium tremens. Severe withdrawal / delirium tremens usually develop after 72 hours but can be sooner. Clinical features include; marked tremor, confusion, disorientation, agitation, restlessness, fearfulness, visual and auditory hallucinations, delusions, autonomic disturbances, tachycardia, sweating, fever and dehydration. Persons consuming more than 16 units per day (half to one bottle of spirits per day or equivalent) are particularly at risk. Other risk factors include severe dependence, previous history of DTs, older age and coexisting medical conditions such as infection. 1.2 Pharmacological management of alcohol detoxification

Which drug to use? Benzodiazepines are the treatment of choice in the management of alcohol withdrawal.

Management Guidelines Alcohol dependent patients that exhibit withdrawal features or are at risk of developing withdrawal should be prescribed benzodiazepines, (i.e. diazepam or chlordiazepoxide). Dosage should be individually titrated and will depend on severity of dependence, withdrawal severity, gender, size, weight, general health and liver function. The following regime for inpatient detoxification is a guideline only:

A typical inpatient regime for a severely dependent adult male would be: Day 1: Diazepam, 20 mg qds Day 2: Diazepam, 15-20 mg qds Day 3: Diazepam, 15 mg qds Day 4: Diazepam, 10 mg qds Day 5: Diazepam, 10 mg tds Day 6: Diazepam, 10 mg bd Day 7: Diazepam, 10 nocte

Females, the elderly and those with milder dependence / withdrawal should be commenced on a lower starting dose, e.g. diazepam 10-15 mg qds, and reduced accordingly.

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Alternatively, chlordiazepoxide can be used - (5 mg diazepam is approximately equivalent to 10 - 15 mg chlordiazepoxide). A sample regime for a moderately dependent adult male would be: Day 1: Chlordiazepoxide 30 mg qds Day 2: Chlordiazepoxide, 25 mg qds Day 3: Chlordiazepoxide, 20 mg qds Day 4: Chlordiazepoxide, 15 mg qds Day 5: Chlordiazepoxide, 10 mg tds Day 6: Chlordiazepoxide, 10 mg bd Day 7: Chlordiazepoxide, 10 nocte There may be need for dose flexibility especially during the first 48hrs as dosage is titrated against withdrawal symptoms / over-sedation. Patients should therefore be regularly and closely monitored. In very severe withdrawal, (e.g. DTs), additional ‘as required’ oral doses of diazepam (or IM lorazepam) may be necessary for the first few days. Similarly, dosage will need to be reduced in response to excessive drowsiness or over-sedation. Special caution is necessary in the case of severe liver impairment (eg cirrhosis) as the metabolism of benzodiazepines may be reduced and lead to over-sedation. (Lorazepam or oxazepam may be suitable alternatives to diazepam and chlordiazepoxide in these cases). For withdrawal fits or status epilepticus use rectal diazepam (Stesolid®) 10 mg (in view of risk of respiratory depression with IV route). This dose may be repeated at 15-minute intervals where necessary. In the case of severe behavioural disturbance use oral haloperidol 5-10 mg. However, be aware that use of antipsychotics may lower the seizure threshold. For severe vomiting use metoclopramide 10 mg IM for up to 5 days or cyclizine 50 mg IM. NB. Haloperidol also has anti-emetic action and therefore if used for behavioural disturbance might also combat any nausea and vomiting. If it does not, it should not be used in combination with metoclopramide as this greatly increases the risk of extrapyramidal side effects, instead of cyclizine.

What dose to start on? Scores on the Severity of Alcohol Dependence Questionnaire (SADQ) and / or units of alcohol per week can provide a rough guide to deciding the starting dose of benzodiazepines, (i.e. what point to start on the Alcohol Detoxification Prescription Chart *). However, this is no substitute for careful, regular observation and monitoring, especially in the first day or two. *Special prescription forms for prescribing benzodiazepines and vitamin supplements for alcohol detoxification are available.

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Table 5: Guide to starting dose of benzodiazepines for alcohol detoxification (adult male)

MILD MODERATE SEVERE V SEVERE

SADQ 15 15-30 30-40 40+

UNITS/WEEK 100 100-200 200+ 250+

Diazepam 5-10mg QDS

10-15mg QDS

20mg QDS

20mg QDS

Chlordiazepoxide 10-15 mg QDS

25-30mg QDS

40-50 mg QDS

50mg QDS

Severity of Alcohol Dependence Questionnaire (SADQ) (See appendix 1). The Severity of Alcohol Dependence Questionnaire is a self-administered and reliable instrument to measure the severity of alcohol dependence. It can also be used to predict the degree of withdrawal symptoms and help in judging medication. The amount of alcohol consumed per week (units/week) can also give estimate of dependence and likelihood of withdrawal. (See appendices 2 and 3). Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar). This scale can sometimes be used to assist in the assessment of withdrawal symptoms and their severity. A simplified version of it can be found on the reverse of the special prescription forms for inpatient alcohol detoxification. Patients should be breathalysed and the first dose of benzodiazepine given if serial readings show a falling alcohol concentration and there is no evidence of gross alcohol intoxication. Caution is needed if the patient shows a high alcometer level (e.g. 0.35mg/L breath alcohol, BrAC). 1.3 Prevention of Wernicke-Korsakoff syndrome Wernicke’s encephalopathy is a common and potentially fatal consequence of alcoholism. Failure to prevent or successfully treat Wernicke’s encephalopathy can lead to the development of Korsakoff’s psychosis, which may be extremely difficult to manage and represents a huge healthcare burden. Wernicke’s encephalopathy (acute confusion, ataxia, ophthalmoplegia) may be difficult to recognise /diagnose as all 3 features are only present in 10% of cases. Vitamin Supplements: It is important to note that oral thiamine is poorly absorbed in alcohol dependent patients. Therefore all patients undergoing inpatient detoxification should receive IM/IV high potency vitamin B complex preparations (Pabrinex®) for five days. On admission, the first dose should be administered before any food is offered. This should be followed by oral thiamine (vitamin B1) 100mg TDS for a minimum of six weeks before reviewing if Wernicke’s encephalopathy and Korsakoff’s psychosis (amnesia, time disorientation and confabulation) are to be prevented. Anaphylactic reactions are rare (1 in 5 million for IM, 1 in 250,000 for IV) but facilities for treating anaphylactic reactions must be readily available whenever IM / IV preparations of vitamin B complex preparations (Pabrinex®) are used. Note: the first dose of parenteral vitamins should be given before the first meal of the day. IM is the more common and preferred route of administration. Pabrinex® IM should be given in divided doses and no more than 4ml volume per injection site. If the IV

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route is used then drip infusion using 50-100 mls of normal saline for dilution, over a period of 30 minutes is the preferred method. 1.4 General management All patients, and especially those with marked withdrawal, need close observation and monitoring of vital signs and level of consciousness, correction of dehydration or electrolyte imbalance and treatment of concurrent conditions (e.g. infection, hypoglycaemia, hepatic failure, GI bleeding etc). Patients should be orientated and reassured that any distressing symptoms will eventually settle. An explanation of the symptoms and their relationship to excessive alcohol consumption should be given. If the patient is discharged prior to completion of detoxification, clear instructions should be given regarding medication on discharge and, where necessary, arrangements made for on going supervision of detoxification (e.g. by the GP). This may also be an opportunity for discussion of follow-up psychosocial interventions, counselling, relapse prevention etc. Directive counselling during the process of detoxification can enhance a patient’s motivation to continue the treatment. 2. Pharmacological Management used in Relapse Prevention in alcohol dependence Disulfiram, acamprosate and naltrexone are used for maintaining abstinence in alcohol dependent patients. Acamprosate is covered here. 2.1 Acamprosate Acamprosate is an adjunctive treatment for alcohol dependence combined with counselling. Before being commenced on acamprosate the patient must:

Have a physical examination and liver function tests ordered. Acamprosate is contraindicated in patients with known hypersensitivity, pregnancy/ breastfeeding, cases of severe hepatic failure and renal impairment (serum creatinine>120 micromol/L) Dosage is 2 tablets three times daily with meals in subjects weighing 60 Kg or more; reducing to 2 tablets in the morning, 1 tablet at noon and 1 tablet at night in subjects weighing less than 60 kg. Treatment is usually initiated as soon as possible after the withdrawal period and should be maintained if the patient relapses. There is some evidence that prescribing at the beginning of an alcohol detox can be potentially neuroprotective so this may be considered. The recommended treatment period is 1 year, although continued alcohol abuse negates the therapeutic benefit of acamprosate. Side effects of acamprosate commonly include gastrointestinal disorders and skin rashes. Very rarely hypersensitivity reactions occur.

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3. Benzodiazepine withdrawal The onset, nature and extent of withdrawal symptoms experienced are influenced by the type of benzodiazepine used and whether medication is used to assist withdrawal. During un-assisted withdrawal from short-acting benzodiazepines such as lorazepam, withdrawal symptoms may appear within hours. However, it may take several days/weeks for the benzodiazepine withdrawal syndrome to develop after stopping a long-acting drug such as diazepam. The withdrawal symptoms typically last at least four weeks after stopping medication. A significant number of patients will suffer protracted withdrawal symptoms and a return to full normal health may take several months.

Many symptoms of benzodiazepine withdrawal are similar to those experienced by persons suffering from anxiety disorders. These symptoms include anxiety, insomnia, depression, tremor, poor concentration, panic attacks and palpitations. Other symptoms, namely perceptual distortions, depersonalisation, paraesthesia, muscle pain, myoclonic jerks, visual disturbances (blurring of vision, photophobia) and nasal congestion appear to be more specific of benzodiazepine withdrawal. A minority of patients will develop severe withdrawal complicated by grand-mal seizures and/or delirium.

Table 3: BENZODIAZEPINE ABSTINENCE SYMPTOMS

Short Term* Long Term** Psychological Anxiety Apprehension Perceptual distortion Tremor Hallucinations, delusions Insomnia Agoraphobia Nausea Depression Vomiting Unreality Convulsions Depersonalisation Paranoid thoughts and

feelings of persecution Craving Somatic

Paraesthesia Pain Ataxia Visual disturbances Gastrointestinal

symptoms Influenza-like symptoms

Metabolic and endocrine symptoms

*Symptoms may occur 3 to 10 days following discontinuation of treatment with a long-acting benzodiazepine and within 24 hours after abrupt withdrawal of a benzodiazepine with a short half-life.

** These may last for months, and may appear in the first 3 to 10 days.

3.1 Benzodiazepine stabilisation – (Inpatient) Benzodiazepine stabilisation may be carried out prior to benzodiazepine detoxification, to establish the baseline dose from which drug withdrawal will be commenced. Diazepam is the drug of choice to assist benzodiazepine detoxification

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as it has a long duration of action and therefore produces a smoother more protracted withdrawal. The patient’s reported total benzodiazepine daily intake should be converted to a diazepam equivalent dose which is set as the maximum amount of diazepam that may be dispensed within a 24-hour period. (See guide below to aid conversion to diazepam equivalent dose). It should be borne in mind that most patients rarely need benzodiazepines in dosage approximating to what they report using. For example, one study found little relationship between reported use and amount of diazepam for stabilization. Furthermore, the majority of patients can be comfortably and safely stabilised on diazepam 40–80 mg daily, regardless of their use prior to admission. The equivalent diazepam dose should therefore be considered to be an absolute maximum and the amount and number of doses of diazepam given should be titrated against objective and subjective symptoms of benzodiazepine withdrawal. It is wiser to give smaller divided doses and ‘as required’ doses initially when trying to establish stabilisation / tolerance. 3.2 Doses of benzodiazepines that are approximate equivalent to diazepam 5 mg: Chlordiazepoxide 15 mg Clonazepm 0.5mg-1mg Loprazolam 0.5mg – 1 mg Lorazepam 500 micrograms Nitrazepam 5 mg Oxazepam 15 mg Temazepam 10 mg The period of benzodiazepine stabilisation should last three days. During the first day patients should be administered small doses of diazepam, (range 10- 20 mg), as frequently as required (e.g. qds +prn). By day four the patient can be administered their total daily requirement of diazepam in one or two doses if they wish. 3.3 Benzodiazepine detoxification – (Inpatient) This involves daily reduction from an individually tailored starting dose of diazepam that has been established either before admission or following a three-day period of inpatient assessment. The length of the withdrawal schedule will depend on the dose of diazepam from which withdrawal is commenced. The withdrawal schedules detailed below should usually be followed (i.e. reduction by 10mg daily until dose of 40mg is reached, then reduction by 5mg daily). Once stabilised, the daily dose can be split, (if requested), into two approximately equal doses, the first to be taken in the morning and the second in the evening.

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Table 4: TYPICAL BENZODIAZEPINE WITHDRAWAL SCHEDULE FOR INPATIENTS USING DIAZEPAM (MIXTURE)

DAY

8am

NOON

5pm

10pm

TOTAL

1-3

4

5

6

7

8

9

10

11

12

13

14

15

16

20mg

20mg

20mg

10mg

10mg

10mg

10mg

5mg

5mg

5mg

5mg

5mg

- -

20mg

10mg

10mg

10mg

10mg

5mg

5mg

5mg

5mg

- - - - -

20mg

20mg

10mg

10mg

10mg

10mg

5mg

5mg

5mg

5mg

- - - -

20mg

20mg

20mg

20mg

10mg

10mg

10mg

10mg

5mg

5mg

5mg

5mg

5mg

5mg

80mg

70mg

60mg

50mg

40mg

35mg

30mg

25mg

20mg

15mg

10mg

10mg

5mg

5mg

If the patient is pregnant then the withdrawal schedule should be extended to last at least 20 days, regardless of the initial diazepam dose. If the patient is struggling to tolerate their withdrawal symptoms, they may be stabilised on the previous day’s diazepam dose for two days. This serves to prevent self-discharge and, in the case of pregnant women, foetal distress. Convulsions should be treated with 10 mg diazepam administered rectally. If a patient suffers a seizure they need to be reviewed by the ward doctor and further reductions in the dose of diazepam should be delayed for 48 hours. 4. References National Institute for Health and Clinical Excellence, Alcohol-use disorders 2010 & 2011 Drug Misuse and Dependence-Guidelines on Clinical Management (2007) Alcohol and Brain Damage in Adults Royal College of Psychiatrists May 2014 British National Formulary (Current edition).

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Appendix 1

THE SEVERITY OF ALCOHOL DEPENDENCE QUESTIONNAIRE

Referred to as the S.A.D.Q., this is a standardized assessment tool used for measuring a patient’s alcohol dependence. (Stockwell et al 1979). It is widely employed for clinical work and research purposes and focuses on measuring the following: Physical withdrawal Affective withdrawal Drinking to avoid/relief of withdrawal Quantity and frequency of intake Rapidity of onset of withdrawal symptoms following a period of abstinence The patient completes the questionnaire but may need assistance The range of scoring is zero to 60 A score of zero to 30 indicates mild to moderate dependence A score of 30+ indicates severe dependence Scoring is: ALMOST NEVER SOMETIMES OFTEN NEARLY ALWAYS

0 1 2 3

THIS IS A CONFIDENTIAL QUESTIONNAIRE THAT IS DESIGNED TO ASSIST IN

ASSESSING THE DEGREE AND NATURE OF Alcohol Dependence

It should be completed prior to your appointment and brought with you.

If you have any difficulties completing this questionnaire we will help you at the time

of your appointment.

NAME: M F

First of all, we would like you to recall a recent month when you were drinking heavily

in a way which, for you, was fairly typical of a heavy drinking period.

Please fill in the month and the year.

MONTH: YEAR:

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PLEASE ANSWER EVERY QUESTION BY PUTTING AROUND A RING AROUND THEMOST

APPROPRAITE ANSWER.

1. During a heavy drinking period, I wake up feeling sweaty:

ALMOST NEVER SOMETIMES OFTEN NEARLY ALWAYS

2. During a heavy drinking period, my hands shake first thing in the morning:

ALMOST NEVER SOMETIMES OFTEN NEARLY ALWAYS

3. During a heavy drinking period, my whole body shakes violently first thing in the

morning if I do not have a drink:

ALMOST NEVER SOMETIMES OFTEN NEARLY ALWAYS

4. During a heavy drinking period, I wake up absolutely drenched in sweat:

ALMOST NEVER SOMETIMES OFTEN NEARLY ALWAYS

The following statements refer to moods and states of mind you may experienced

first thing in the morning during these periods of heavy drinking.

5. When I am drinking heavily I dread waking up in the morning:

ALMOST NEVER SOMETIMES OFTEN NEARLY ALWAYS

6. During a heavy drinking period, I am frightened of meeting people first thing in

the morning:

ALMOST NEVER SOMETIMES OFTEN NEARLY ALWAYS

7. During a heavy drinking period, I feel at the edge of despair when I awake:

ALMOST NEVER SOMETIMES OFTEN NEARLY ALWAYS

8. During a heavy drinking period, I feel very frightened when I awake:

ALMOST NEVER SOMETIMES OFTEN NEARLY ALWAYS

9. During a heavy drinking period, I like to have a morning drink:

ALMOST NEVER SOMETIMES OFTEN NEARLY ALWAYS

10. During a heavy drinking period, I always gulp my first few morning drinks down as

quickly as possible:

ALMOST NEVER SOMETIMES OFTEN NEARLY ALWAYS

11. During a heavy drinking period, I drink in the morning to get rid of the shakes:

ALMOST NEVER SOMETIMES OFTEN NEARLY ALWAYS

12. During a heavy drinking period, I have a strong craving for a drink when I awake:

ALMOST NEVER SOMETIMES OFTEN NEARLY ALWAYS

13. During a heavy drinking period, I drink more than a quarter of a bottle of a spirits

per day (4 doubles or 1 bottle of wine or 4 pints beer:

ALMOST NEVER SOMETIMES OFTEN NEARLY ALWAYS

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14. During a heavy drinking period, I drink more than half a bottle of spirits per day (or

2 bottles of wine or 8 pints of beer):

ALMOST NEVER SOMETIMES OFTEN NEARLY ALWAYS

15. During a heavy drinking period, I drink more than one bottle of spirits per day (or 4

bottles of wine or 15 pints of beer):

ALMOST NEVER SOMETIMES OFTEN NEARLY ALWAYS

16. During a heavy drinking period, I drink more than 2 bottles of spirits per day (or 8

bottles of wine or 30 pints of beer):

ALMOST NEVER SOMETIMES OFTEN NEARLY ALWAYS

IMAGINE THE FOLLOWING SITUATION:

1. You have been COMPLETELY OFF drink for FEW WEEKS

2. You then drink VERY HEAVILY for TWO DAYS.

HOW WOULD YOU FEEL THE MORNING AFTER THOSE TWO DAYS OF HEAVY DRINKING?

17. I start to sweat:

NOT AT ALL SLIGHTLY MODERATELY QUITE A LOT

18. My hands would shake:

NOT AT ALL SLIGHTLY MODERATELY QUITE A LOT

19. My body would shake:

NOT AT ALL SLIGHTLY MODERATELY QUITE A LOT

20. I would be craving for a drink:

NOT AT ALL SLIGHTLY MODERATELY QUITE A LOT

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Appendix 2

Aquarius Unit Reckoners These tables show how many units are in a pint, bottle, can or glass of different strength drinks. Check the label or can for the strength of a drink (usually shown as % alcohol by volume or %ABV) and the volume of the container, and use this information to find the number of units in the relevant table.

Beer, Lager and Cider

%ABV 1% 2% 3.5% 4.5% 5.5% 6% 7% 8% 9% 9.5%

Pint (568ml) 0.6 1.1 2 2.6 3.1 3.4 4 4.5 5.1 5.4

Large can (500ml) 0.5 1 1.8 2.3 2.8 3 3.5 4 4.5 4.8

Can (440ml) 0.4 0.9 1.5 2 2.4 2.6 3.1 3.5 4 4.2

Bottle (330ml) 0.3 0.7 1.2 1.5 1.8 2 2.3 2.6 3 3.1

Small Bottle (275ml) 0.3 0.6 1 1.2 1.5 1.7 1.9 2.2 2.5 2.6

Wine

%ABV 8% 9% 10% 11% 12% 13% 14%

Bottle (750ml) 6 6.8 7.5 8.3 9 9.8 10.5

Large glass (250ml) 2 2.3 2.5 2.75 3 3.3 3.5

Small glass (175ml) 1.4 1.6 1.8 1.9 2.1 2.3 2.5

V. small glass (125ml) 1 1.1 1.3 1.4 1.5 1.6 1.8

Fortified Wines & Aperitifs (eg Sherry, Martini)

%ABV 15% 16% 17% 18% 20% 24%

Bottle (750ml) 11.3 12 12.8 13.5 15 18

Small glass (50ml) 0.8 0.8 0.9 0.9 1 1.2

Spirits %ABV 37.5% 40% 50%

Bottle (700ml) 26.3 28 35

Large single* (35ml) 1.3 1.4 1.8

Single* (25ml) 0.9 1 1.3

* Licensed premises may choose whether to serve spirits in

either 25ml or 35ml measure, and multiples of these.

Alco-pop

%ABV 4% 4.5% 5% 5.5% 6%

Bottle or can (330ml) 1.3 1.5 1.7 1.8 2

Bottle (275ml) 1.1 1.2 1.4 1.5 1.7

If your drink is not here, this is how to calculate the number of units in any container:

(Volume in ml) X (strength in % abv) divided by 1000 = Units of Alcohol eg a 250ml bottle of 4% abv lager contains exactly 1 unit of alcohol ( (250 x 4)/1000 = 1)

The Aquarius website www.aquarius.org.uk

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Appendix 3

1 Standard Unit – 10ml (8g) Absolute Alcohol

or

or

Beer

(3.5%)

½ Pint =

1 unit

Wine (8%)

125ml

1 glass =

1 unit

Spirit

(40%)

1 x 25ml

measure

=

1 unit

750ml

Wine

(12%)

= 9 units

or

700ml

Spirits

(40%)

= 28

units