10. Pharmacological interventions

How to provide pharmacological interventions for alcohol dependence, covering specific medications such as benzodiazepines for withdrawal management, acamprosate and naltrexone for preventing relapse and thiamine supplementation to prevent neurological complications.

10.1 Main points

Pharmacological interventions are used:

for medically assisted withdrawal from alcohol
to prevent and manage specific complications of withdrawal from alcohol
to prevent and treat the consequences of thiamine deficiency, including Wernicke’s encephalopathy, in people at high-risk who continue to drink alcohol, as well as those undergoing withdrawal
to reduce craving, prevent relapse and promote abstinence
to reduce alcohol consumption in specific groups of people who have a high drinking risk level

Pharmacological interventions can be provided in a range of settings. Clinicians will need to plan the setting and regimens for interventions, based on a full assessment of the patient, considering a range of factors including:

severity of dependence
complexity of need including co-occurring physical and mental health conditions
skills and resources needed to provide the intervention effectively and safely

The main purpose of medication in medically assisted withdrawal is to help people with alcohol dependence to stop drinking without experiencing withdrawal complications. These can include seizures, delirium tremens and Wernicke’s encephalopathy.

Benzodiazepine reducing regimens are the standard pharmacological treatment to manage withdrawal from alcohol. Regimens can be fixed-dose or symptom-triggered.

If a person experiences any severe withdrawal complications during medically assisted withdrawal in the community, it should be treated as an emergency. You should provide appropriate emergency care (as available) and call an ambulance.

The choice of relapse prevention medication will need to be based on full assessment of the patient, their preference and ability to adhere to the regimen.

Clinicians should provide thiamine supplementation to all people about to undergo or undergoing medically assisted withdrawal. However, it’s important to offer thiamine prophylaxis to all people who drink harmfully and dependently, whether or not they intend to undergo medically assisted withdrawal.

Where possible, clinicians should explore options for medication to support relapse prevention and promote abstinence with the person before they start making plans for medically assisted withdrawal.

Particular considerations apply when using pharmacological interventions for people from specific groups or with co-occurring conditions (see section 10.6 for guidance on this).

10.2 Context

10.2.1 General principles

When pharmacological interventions are used, they should be as part of a broad treatment plan where a person’s goals have been agreed.

You should choose the pharmacological intervention based on a thorough assessment and be clear about the goals and purpose for prescribing medication, considering the patient’s views and preferences.

When using medication, you will need to monitor for effectiveness and for any unwanted effects in the patient. People who are particularly unwell will need specifically skilled nursing and medical care, for example, if they are in severe acute withdrawal.

Where there is a choice of recommended medications or regimens that are equally effective, it is usually better for clinical teams to work with the option with which they are most experienced. For example, although you can use a range of benzodiazepine drugs (most commonly, chlordiazepoxide or diazepam in the UK) to manage acute alcohol withdrawal, skilled care and monitoring are more important than the choice of medication.

Medication regimens will vary, depending on the setting where they are administered. Each organisation or service should have written policies and procedures on administering pharmacological interventions that are appropriate to the setting and level of competence of the staff.

Prescribers should adhere to the:

General Medical Council (GMC) guidance Good practice in prescribing and managing medicines and devices
Royal Pharmaceutical Society’s prescribing competency framework
British National Formulary (BNF) guidance on non-medical prescribing, where appropriate

Clinicians should administer medication in line with Royal Pharmaceutical Society guidance Professional guidance on the administration of medicines in healthcare settings (PDF, 319KB).

You should also be aware of potential interactions between alcohol and prescribed drugs. You can view this information on the BNF website.

You should provide information about medication in a way that is accessible to the person, considering:

their preferred language
their level of literacy
any sensory disability
any cognitive impairment
any neurodiversity

In some cases, you may need to determine whether the patient has the mental capacity to consent to medical treatment. You can find information on mental capacity in annex 1 on relevant legislation and guidance.

10.2.2 Off-label or unlicensed use of medicines: prescribers’ responsibilities

There are situations when clinicians might decide that using unlicensed medicines or using medicines outside the terms of the licence (known as off-label use) is in the best interest of the patient, based on available evidence.

When prescribing unlicensed or off-label medications, prescribers should be aware of their responsibilities under:

GMC guidance
local organisational policies
the Medicines and Healthcare products Regulatory Agency (MHRA) guidance Off-label or unlicensed use of medicines: prescribers’ responsibilities

10.2.3 The importance of setting and staff skills

Pharmacological interventions take place in a variety of settings, including:

primary care
community alcohol treatment services
specialist inpatient units
acute (general) hospitals
mental health inpatient units
prisons

It is important that the setting in which you deliver a pharmacological intervention is the appropriate place for the intervention. For example, some community alcohol treatment services are well set up to administer oral or intramuscular thiamine on-site for patients who continue to drink and are at high risk of Wernicke’s encephalopathy (WE). Other alcohol services may need to make alternative arrangements. Most specialist inpatient units will need to transfer people to acute general hospital settings to manage severe medical complications, such as delirium tremens or WE. Other specialist inpatient units that are closely aligned to general hospitals may be able to manage these complications without transfer.

This chapter goes on to describe the approaches a service can take, depending on the setting and skill-set of the staff. It is important that:

staff responsible for assessing and managing should be clinicians competent in diagnosing and assessing alcohol dependence and withdrawal symptoms
the setting in which the intervention is taking place is appropriate for the intervention and for the patient’s needs
the service provider has clinical governance, supervision and assurance systems in place to ensure staff are appropriately skilled and settings are appropriate

10.2.4 Setting for medically assisted withdrawal based on severity of dependence and complexity of need

Planning the setting and regimens

Clinicians will need to plan the setting and regimens for medically assisted withdrawal based on:

the patient’s severity of dependence
withdrawal history
all assessed patient risk factors including co-occurring physical and mental health conditions
the patient’s needs and circumstances

You can find guidance on assessing someone for medically assisted withdrawal in section 11.5 in chapter 11 on community based medically assisted withdrawal and chapter 12 on specialist inpatient medically assisted withdrawal.

People with moderate alcohol dependence (who typically drink 15 to 30 units per day and score between 15 and 30 on the Severity of Alcohol Dependence Questionnaire (SADQ)) should be offered an assessment for community medically assisted withdrawal.

Criteria for specialist inpatient medically assisted withdrawal

Clinicians should base decisions on whether to refer people for specialist inpatient medically assisted withdrawal on individual clinical assessment. But they should consider specialist inpatient withdrawal weighing up the risks and benefits of that setting for people who meet one of more of the criteria below.

These criteria are based on the National Institute for Health and Care Excellence (NICE) clinical guideline Alcohol-use disorders: diagnosis, assessment and management of harmful drinking (high-risk drinking) and alcohol dependence (CG115) and clinical consensus from the guidelines development group.

They drink over 30 units of alcohol per day or have a score of more than 30 on SADQ (indicating severe dependence). Clinicians should normally consider inpatient medically assisted withdrawal for people who experience severe dependence. But if the person does not have any complex needs or significant comorbidities, it can be appropriate to offer them a community-based medically assisted withdrawal. A decision to do this should be based on individual assessment by a clinician with appropriate training and expertise in managing withdrawal for people with severe alcohol dependence and comorbidities.

They have a history of seizures, or experience of withdrawal-related seizures or delirium tremens during previous assisted withdrawal programmes.

They are assessed as at high risk of WE. Based on individual assessment, it may be possible to offer them medically assisted withdrawal in the community if intramuscular thiamine is available on site and there is a sufficiently skilled, trained and resourced team to administer it. Clinicians should follow guidance in section 10.4.3 on WE and medically assisted withdrawal.

They have a co-occurring substance use problem, including harmful or dependent use of illicit drugs, prescribed, or over the counter medication, which requires management, or concurrent medically assisted withdrawal from alcohol and one or more substances.

They have a severe mental health condition (for example, untreated psychosis, severe depression or suicidal ideation) that makes medically assisted withdrawal in a community or residential setting potentially unsafe.

They have a significant physical health condition (for example, chronic liver disease, malnutrition, congestive cardiac failure ,or unstable angina or chronic lung disease) that makes medically assisted withdrawal in a community or residential setting potentially unsafe.

They have a significant learning disability or cognitive impairment.

They are pregnant.

There is guidance on delivering medically assisted withdrawal in inpatient settings in chapter 12 on specialist inpatient medically assisted withdrawal and chapter 16 on acute hospital settings.

Lower threshold referrals

Clinicians should consider a lower threshold for referring vulnerable groups and people who are frail to specialist inpatient medically assisted withdrawal. This includes:

people experiencing homelessness
older people
children and young people
people with established liver disease

People in each of these groups are very likely to require closer monitoring (for safety reasons) than can be provided in a community medically assisted withdrawal. Additionally, people experiencing homelessness are unlikely to have a sufficiently safe and stable home environment to manage community-based medically assisted withdrawal.

Support for community medically assisted withdrawal

During community medically assisted withdrawal, an appropriate family member or other support person should normally stay with the person, for support and to call an ambulance in an emergency. Where an appropriate family member or support person is not available, the person should normally be offered medically assisted withdrawal in a residential setting. However, the clinician can work with the person to assess their relative risks and benefits of a community-based medically assisted withdrawal, considering:

severity of alcohol dependence
history of withdrawal symptoms
co-occurring physical and mental health conditions
other risk factors

If the person experiences severe complications in the community, they should be immediately admitted to hospital.

Chapter 11 on community-based medically assisted withdrawal gives detailed guidance on delivering community-based medically assisted withdrawal.

10.2.5 Specific groups

Specific considerations apply when using pharmacological interventions for:

young people
older adults
women and those who are pregnant
people with co-occurring physical or mental health problems or other complexities

You can read more about considerations for specific groups in section 10.6, which you should read along with the guidance on specific pharmacological interventions below.

10.3 Prescribing medication for management of withdrawal from alcohol

It is important to read this section along with section 10.4 on preventing complications of withdrawal. Depending on your setting, you should also read:

chapter 11 on medically assisted withdrawal in the community
chapter 12 on specialist inpatient medically assisted withdrawal units
section 16.8 on medically assisted alcohol withdrawal and section 16.9 on withdrawal complications in chapter 16 on alcohol care in acute hospitals

10.3.1 Main purpose of medication in medically assisted withdrawal

The main purpose of medication in medically assisted withdrawal is to enable people with alcohol dependence to stop drinking without experiencing complications of withdrawal, which include:

seizure
delirium tremens
WE

Medication also eases discomfort and distress associated with withdrawal and so helps the person to plan with confidence to prevent future relapses.

10.3.2 Planned and unplanned withdrawal

This section provides guidance on planned medically assisted withdrawal following assessment and preparation. Section 16.7.7 in chapter 16 on acute hospital settings provides guidance on unplanned medically assisted withdrawal in hospital.

If a patient has stopped drinking in an unplanned way and is beginning to experience withdrawal symptoms, which are not yet acute, you should tell them about the risks of stopping drinking suddenly, which can lead to withdrawal complications. Withdrawal symptoms can include:

sweating
shaking
palpitations
headache
nausea or vomiting
anxiety or agitation
insomnia or disturbed sleep

you should tell them about the risks of stopping drinking suddenly (which can lead to withdrawal complications). You should also consider offering an assessment for a planned medically assisted withdrawal.

If the person is severely alcohol dependent, it may be appropriate for them to continue to drink at a steady pace (to avoid potential complications), avoiding episodes of increased heavy alcohol use or periods without alcohol until they can access medically assisted withdrawal. In this situation, you should arrange access to medically assisted withdrawal as quickly as possible.

If the person is mildly or moderately alcohol dependent and does not have any risk factors for complications in withdrawal, you can advise them to cut down gradually while they are waiting for medically assisted withdrawal if they want to do this, with the support of the alcohol service.

There is guidance on assessing for suitability and safety when stopping drinking gradually in sections 8.5 and 8.6 in chapter 8 on harm reduction.

Sometimes, a patient might present to a community treatment service when they are already in complicated acute withdrawal. Symptoms of complicated acute withdrawal include intense shaking and may include:

seizures
delirium tremens
suspected WE

In this situation, you should arrange for the patient to be transferred to an appropriate setting immediately. Patients in the community who experience severe withdrawal complications should be transferred to an acute hospital setting.

You can find guidance on dealing with acute alcohol withdrawal in section 16.7.7 in chapter 16 on acute hospital settings.

10.3.3 Benzodiazepine withdrawal regimens

Benzodiazepine reducing regimens are the standard pharmacological treatment of choice to manage withdrawal from alcohol. The choice of specific regimen will depend on the individual and the setting. In all settings, regular skilled monitoring of symptoms and of the effects of medication is an essential component of care.

For planned medically assisted withdrawal, selecting an appropriate setting for the person is an important consideration. See section 10.2.4 for guidance on setting.

10.3.4 Choice of regimen

Fixed dose regimens (with a specified schedule of reducing daily dose, subject to daily review) are suitable for medically assisted withdrawal in the community.

The initial dose of medication should be titrated to the severity of a person’s alcohol dependence or their regular daily level of alcohol consumption. There are example regimens provided in section 10.7 on benzodiazepine withdrawal regimens.

Fixed-dose regimens should include some flexibility:

to give additional ‘top-up’ doses in case the person’s symptoms are not adequately controlled
to reduce the dose to avoid over-sedation before the next daily review

This flexibility is supported by clinical consensus of the guidelines development group.

The prescribing regimen can include additional doses and the person supporting the patient can be advised on the situations in which this should be given. For instance, if there are breakthrough withdrawal symptoms present in the morning before the reviewing team are able to attend. If the additional dose is used, the monitoring team should review whether the prescribed doses are adequate or whether the regimen should be reviewed by the prescriber.

In inpatient settings, you can use either fixed dose regimens or symptom-triggered regimens. In contrast to fixed dose regimens, the symptom-triggered approach does not follow a pre-planned reduction schedule but has a flexible dosing system in response to careful monitoring of the person’s withdrawal symptoms. A symptom-triggered approach only continues as long as the patient shows withdrawal symptoms. This is a specialist approach that requires all team members to be trained to ensure that it can be applied consistently and safely.

Hospitals intending to use symptom-triggered regimens should consider investing in additional training and competency assessment to ensure that this can be done safely. One of the roles of a specialist alcohol care team (ACT) can be to support safe and consistent use of this approach. However, in hospitals where there is no ACT or suitably trained staff, it is more appropriate to use fixed-dose regimens with daily review.

The quality of monitoring of the person’s response to medication is important with both fixed dose and symptom-triggered regimens.

10.3.5 Choice of medication

Chlordiazepoxide, diazepam and other benzodiazepines

Chlordiazepoxide or diazepam are the most commonly used benzodiazepines. There are example regimens for both of these in section 10.7.

You can choose benzodiazepines with a shorter half-life, such as oxazepam, for people who potentially metabolise medication more slowly, such as those with extensive liver disease or older patients. This is to avoid patients gradually becoming over-sedated. However, you can also use chlordiazepoxide successfully for these patients, and the quality, level and skill of monitoring is more important than the choice of benzodiazepine.

Chlordiazepoxide and diazepam are recommended by NICE CG115 and are licensed for use in medically assisted withdrawal. Other recommended benzodiazepines do not have a specific license but may be used for this purpose (see section 10.2.2 on off-label and unlicensed prescribing).

You should be aware of the MHRA safety alert for the use of benzodiazepines and opioids.

Chlordiazepoxide and possible risk of genotoxicity (damage to genetic information)

Chlordiazepoxide should not be used during pregnancy, especially during the first and last trimesters unless the clinical condition of the woman requires treatment with chlordiazepoxide. You can find the available evidence on the safety of chlordiazepoxide in the summary of product characteristics for Librium 5mg capsules.

The European Medicines Agency (EMA) safety working party and non-clinical working party issued guidance in 2022, revised in March 2023, outlining recommendations on the duration of contraception following the end of treatment with a genotoxic drug (PDF, 1.07MB). Following this, the summary of product characteristics for Librium and some generic chlordiazepoxide varied their licence to implement the guidance.

The change is the result of new EMA guidance, rather than new evidence for the genotoxicity of chlordiazepoxide.

MHRA is reviewing the evidence available on chlordiazepoxide to ensure that appropriate and proportional warnings are implemented as required. MHRA advises that healthcare professionals should continue to use current clinical guidelines while this evaluation takes place.

The risks from continued excessive alcohol consumption and complications from alcohol withdrawal, such as seizures and delirium tremens, are likely to significantly outweigh any potential risk of genotoxic effects from the duration and doses of chlordiazepoxide used for medically assisted withdrawal. When prescribing chlordiazepoxide, the clinician should consider the proportionate balance of risk and discuss this with the patient. Both men and women should be advised about contraception following the end of treatment.

10.3.6 Using carbamazepine as an alternative to a benzodiazepine for managing withdrawal

Carbamazepine is an effective alternative medication for medically assisted withdrawal from alcohol. There are specific (though uncommon) circumstances in which it is a helpful alternative to benzodiazepines. These include situations where the patient has a:

history of adverse reaction or allergy to benzodiazepine drugs (although uncommon, this can be fatal)
preference for carbamazepine (for example, people who have a history of harmful use or dependence on benzodiazepine drugs and who do not want to take them in this context)

You can use carbamazepine in inpatient settings for managing concurrent withdrawal from alcohol and benzodiazepine drugs.

You can find more information on concurrent withdrawal from alcohol and benzodiazepines in section 10.6.1.

Carbamazepine is not licenced for management of withdrawal. See section 10.2.2 on unlicensed or off-label prescribing.

Also, for patients who are pregnant, you should be aware of the MHRA safety review on using antiepileptic drugs in pregnancy.

10.3.7 Using clomethiazole

Clomethiazole was used historically to manage alcohol withdrawal but has been replaced by benzodiazepine drugs, which are safer. NICE CG115 recommends that you should not use clomethiazole for medically assisted withdrawal in the community, where the preferred medication for assisted withdrawal is a benzodiazepine (chlordiazepoxide or diazepam).

In inpatient settings, clomethiazole has no advantages over benzodiazepines in managing withdrawal.

10.4 Prescribing medication to prevent and to manage specific complications of withdrawal

Depending on your setting, you should read this section along with:

chapter 11 on community-based medically assisted withdrawal
chapter 12 on specialist inpatient medically assisted withdrawal
chapter 16 on acute hospital settings

There is detailed guidance on alcohol-related brain damage in chapter 20.

10.4.1 Preventing and managing withdrawal seizures

Withdrawal seizures

Withdrawal seizures are grand mal epileptiform seizures (a seizure causing loss of consciousness and violent muscle contractions) occurring usually 12 to 48 hours after stopping or significantly reducing alcohol consumption. It is important to note that seizures can occur with a breathalyser reading greater than zero in people with severe alcohol dependence. Several seizures may occur, but status epilepticus (a seizure that lasts longer than 5 minutes, or more than one seizure in a 5-minute period, without returning to a normal level of consciousness between episodes) is rare.

If a person has a seizure during medically assisted withdrawal in the community, this should be treated as an emergency. Provide appropriate emergency care as available and call an ambulance.

Preventing withdrawal seizures

Preventing withdrawal seizures is one of the main aims of medically assisted withdrawal. Identifying people at risk will enable you to effectively plan their care, to reduce the likelihood of this complication.

Initial assessment should identify the following risk factors in as much detail as possible, including any history of:

seizures, including withdrawal seizures
epilepsy

Other factors such as electrolyte disturbance can contribute to seizure risk in severe alcohol dependence with comorbid malnutrition, though this is a matter of debate, you should consider detecting and correcting this before planned withdrawal, where this is possible.

People at risk of severe withdrawal should generally undergo medically assisted withdrawal in a specialist inpatient withdrawal unit or in general hospital. Those at high risk are likely to need a higher dose regimen of long-acting benzodiazepine.

There is no evidence to support prophylactic use of additional anticonvulsant medication to prevent seizures in people who are at high-risk, and you should not initiate additional anticonvulsant medication. Your focus should be on adequate dosing with the chosen benzodiazepine, in line with the British Association for Psychopharmacology (BAP) updated guidelines for the pharmacological management of substance abuse, harmful use, addiction and comorbidity (PDF, 1.13MB).

For people who are already on established anticonvulsant medication to treat epilepsy, you should continue the antiepileptic treatment dose along with the medically assisted withdrawal medication. You should then monitor their medication levels to ensure they stay within the therapeutic range.

10.4.2 Preventing and managing delirium tremens

Identifying delirium tremens

Delirium tremens usually emerges between day 2 and 3 (occasionally up to day 5) of alcohol withdrawal in a person with severe alcohol dependence. This is a medical emergency and requires immediate transfer to an inpatient setting with 24 hour medical and nursing care. It is crucial that you are alert to the possibility of delirium tremens developing in people undergoing alcohol withdrawal. One of the main aims of medically assisted withdrawal is to prevent the onset of delirium tremens.

Delirium tremens is a toxic confusional state, characterised by:

disorientation
agitation
tachycardia (heart rate of more than 120 beats per minute)
hypertension (20mmHg (millimetre of mercury) rise in systolic blood pressure)
fever
hallucinations (auditory, olfactory, and visual)
marked tremor
sleeplessness
paranoid ideation

These symptoms may not always all be present at the same time.

Preventing delirium tremens in medically assisted withdrawal

Many potential cases of delirium tremens can be prevented by quickly starting appropriate treatment for withdrawal as set out in section 10.3 and thiamine prophylaxis as set out in 10.4.3 of this chapter.

Risk factors for delirium tremens include:

previous seizures or delirium
many co-occurring physical health problems
low potassium
thiamine deficiency
systemic disease
low magnesium

Under-treated withdrawal is also a significant factor.

If there is high risk of delirium tremens, planned medically assisted withdrawal should take place in a specialist inpatient withdrawal unit with appropriate staffing and facilities, or in an acute hospital setting with alcohol specialist input.

Evidence on the role of magnesium deficiency as a risk factor for delirium tremens is inconclusive and an area of ongoing debate. However, in people with severe alcohol dependence and comorbid malnutrition, consider checking and rectifying magnesium levels as quickly as possible, though this should not delay other treatment. Where magnesium deficiency is identified, you should be mindful of risk and monitor for any signs of the onset of delirium tremens.

Managing established delirium tremens

If the person develops delirium tremens despite preventative efforts as outlined above, you should treat it as a medical emergency. If delirium tremens emerges during medically assisted withdrawal in the community, you must transfer the person to an acute hospital as an emergency.

If the person is being managed in a specialist inpatient medically assisted withdrawal unit that is not in an acute hospital, you should consider transferring the patient to an acute medical setting, depending on resources and staff expertise available to the unit.

NICE clinical guideline Alcohol-use disorders: diagnosis and management of physical complications (CG100) recommends using lorazepam for treatment of delirium tremens and haloperidol as an option where oral lorazepam is declined or symptoms persist. However, the consensus of the alcohol clinical guidelines development group (and clinical guidelines from other countries) is that neuroleptics such as haloperidol should:

not be given as first line treatment or monotherapy for delirium tremens
only be used as an adjunct to benzodiazepine treatment where adequate doses have failed to manage the behavioural disturbance
not replace adequate doses of benzodiazepines

The treatment should be different from that for delirium arising from other causes, and larger doses of benzodiazepines are required (ASAM, 2020; Schuckit, 2014; Mayo-Smith and others, 2004). Haloperidol can lower the threshold for seizures.

There is guidance on the medical and nursing management of delirium tremens in section 16.9.3 on identifying risk and managing delirium tremens in chapter 16 on alcohol care in acute hospitals.

10.4.3 Preventing and managing Wernicke’s encephalopathy

WE is a serious complication of deficiency of thiamine (vitamin B1), for which the most common cause is alcohol dependence. This can result in lasting brain injury, so preventing this complication is vital. See chapter 20 for more detailed guidance on alcohol-related brain damage.

Thiamine is used to:

prevent WE in people at risk (in community or inpatient settings)
treat WE (in an inpatient setting)

WE is a potential complication of alcohol withdrawal and thiamine should be prescribed as part of medically assisted withdrawal to prevent WE from developing. However, WE does not occur only when people stop drinking, and people who are malnourished or have decompensated liver disease remain at risk while they continue to drink alcohol.

People with any degree of risk of WE, who choose not to have parenteral (intramuscular or intravenous) thiamine, should be offered oral thiamine.

This section deals with prophylactic administration of thiamine You can find guidance on treatment of suspected or established WE in section16.9.4 and in section 16.9.3 on identifying risk and managing delirium tremens in chapter 16 on acute hospital settings.

All local areas should have an agreed pathway for provision of preventive intramuscular (IM) or intravenous (IV) thiamine, which ensures that the setting in which it is provided is equipped to respond appropriately in the event of anaphylaxis.

Thiamine prophylaxis to prevent WE

Many people with alcohol dependence are at risk of developing WE due to thiamine deficiency. They may also have deficiencies in other vitamins. You should provide thiamine supplementation as part of any medically assisted withdrawal. However, you should also consider offering thiamine prophylaxis in all people who drink harmfully and dependently, whether or not they intend to undergo medically assisted withdrawal.

The risk of anaphylactic reaction from parenteral (IM or IV) vitamins has sometimes deterred clinicians from using them, but the risks of failing to correct thiamine deficiency are significant. You should consider the following points.

Absorption of oral thiamine from the intestine is saturated at 5 to 10 milligrams (mg) per dose in healthy people and can be reduced to negligible amounts in people with alcohol dependence, especially those with malnutrition. So, the oral route will not be adequate to replace depleted thiamine in a significant proportion of these people (Tallaksen and others, 1993; Weber and Kewitz, 1985).

Thiamine stores need to be replaced as quickly as possible and high circulating levels of thiamine are needed for passive diffusion into the central nervous system (based on clinical consensus of the guidelines development group).

For people who need parenteral thiamine, the risk of anaphylaxis is very low: less than 1 in 5,000,000 for IV infusion and lower still for the IM route (Cook and others, 1998; Thomson and Marshall, 2006).

MHRA has published a drug safety update on allergic reactions to parenteral Pabrinex (thiamine and other vitamins).

Pharmacological regimen for thiamine prophylaxis

The appropriate regimen for thiamine prophylaxis will depend on whether the person:

is considered to be at lower-risk
has no signs of WE but is at high risk of it developing
is showing signs of WE

Thiamine should be given orally or parenterally as described below.

The lower-risk group comprises people who drink harmfully or dependently but who do not have any of the conditions that put them at high-risk. In practice, all people presenting for treatment in community alcohol treatment services, who do not meet criteria for the high-risk regimen, should be given thiamine 50mg oral 4 times daily.

People in the high-risk group can have a range of conditions, including:

significant weight loss
poor diet
low body mass index (BMI) (a BMI score of less than 18)
other signs of malnutrition
memory disturbance
peripheral neuropathy
previous history of complicated withdrawal including WE
decompensated liver disease
long history of harmful drinking and alcohol dependence

In community settings, consider offering prophylactic IM thiamine to people at high risk of WE, following the dosing below.

Give IM thiamine 200mg to 300mg once daily for at least 3 days with daily review and monitoring for signs of WE.

Injections should be given by appropriately skilled, trained and resourced staff.

If the person is significantly underweight with limited tissue for IM injection, has a clotting problem or prefers IV rather than IM thiamine, you should transfer them to an inpatient setting.

IM thiamine should be followed by a course of oral thiamine until holistic review of overall recovery indicates it is no longer necessary.

If you have well-founded nutritional concerns, you can also prescribe a suitable nutritional supplement.

For administration of prophylactic IM or IV thiamine in hospital settings, see section 16.9.4 in chapter 16 on alcohol care in acute hospitals.

Treatment for incipient Wernicke’s encephalopathy

Incipient WE is characterised in most cases by confusion, in some cases with classical symptoms of ataxia (unsteady walking), memory disturbance and ophthalmoplegia (impaired eye movements). People with suspected WE should immediately be transferred to an inpatient setting with 24 hour medical and nursing staffing.

You can find guidance on managing and prescribing for treatment of WE in section 16.9.4 in chapter 16 on alcohol care in acute hospitals.

Preventing Wernicke’s encephalopathy in people who continue to drink alcohol

There are opportunities, in alcohol treatment services, primary care and other community settings, to provide thiamine to people:

in the lower risk group for WE who continue to drink alcohol
at high risk of developing WE even if they intend to continue to drink

In community settings, consider offering:

preventive oral thiamine to people in the lower-risk group
IM thiamine followed by oral thiamine to people at high risk of WE (as described above in this section)

Appropriately skilled and resourced services should assess and consider offering parenteral thiamine to people at high risk when they present to services, even if they do not imminently plan to undergo medically assisted withdrawal. The benefits of this outweigh the low risk of anaphylaxis (see above and chapter 16 on acute hospital settings and chapter 20 on alcohol-related brain damage).

10.5 Pharmacological interventions for preventing relapse and promoting abstinence

10.5.1 Principles for prescribing for relapse prevention and promoting abstinence

Planning medication to support relapse prevention

Medication can be an important addition to psychosocial treatment and recovery plans, yet clinicians often under-use evidence-based pharmacological treatments. This could be because both clinicians and people seeking help are unaware of all the options.

Where possible, you should explore options for medication to support relapse prevention and promote abstinence with the person before you start making plans for medically assisted withdrawal. This allows you to carry out baseline assessments, so you are ready to prescribe in a seamless plan after the end of the patient’s withdrawal. This also allows (off-label) acamprosate treatment to begin before withdrawal. If you need to carry out medically assisted withdrawal without prior planning, you should consider relapse prevention medication before the patient completes withdrawal.

For people with harmful patterns of drinking or with mild alcohol dependence who have not responded to psychological interventions alone, or who have specifically requested a pharmacological intervention, you should consider offering acamprosate or oral naltrexone along with a psychosocial intervention. There is less evidence for acamprosate in the treatment of these groups than that for naltrexone and this would be an off-label use of acamprosate.

Integrating pharmacological and psychosocial interventions in community alcohol treatment services or primary care

Whether through community alcohol treatment or primary care, there should be an agreed local pathway for prescribing relapse prevention medications and partners should share information so they are familiar with a person’s prescribing history. You should prescribe medication for relapse prevention in the context of a psychosocial treatment and recovery plan. This does not mean that you need to provide complex formal psychological treatments, and the lack of specialised approaches should not stop someone accessing relapse prevention medication.

If the person has not received treatment from a specialist alcohol treatment service, their GP should offer them a referral and encourage them to attend the specialist service. If they decline referral, or if they have completed their treatment at a specialist alcohol service, regular monitoring and review by the GP along with supportive contact in primary care will help them to benefit from medication.

If a GP prescribes relapse prevention medication, they should provide information about:

alcohol use disorders
the purpose of the medication
how to manage safe adherence to a medication regimen

The GP can support the person’s treatment by encouraging them to engage with mutual aid groups and peer support organisations. To support treatment effectiveness, it helps to return to the offer of a referral to a specialist alcohol treatment service where appropriate and encourage the person to attend.

10.5.2 First-line pharmacological interventions

Acamprosate and naltrexone are first-line options for pharmacological treatment to support relapse prevention, following successful withdrawal from alcohol for people with moderate to severe dependence.

Acamprosate

This section on acamprosate covers:

indications
baseline investigations and monitoring
dose schedule
suggested dose schedule in renal impairment
prescribing arrangements

Indications

Acamprosate is usually well-tolerated, and mild gastrointestinal disturbance is the most commonly reported side effect (see section on acamprosate in the BAP guidelines (PDF, 1.13MB)). It is a first-line treatment for relapse prevention and you should consider it as an option for all people who are undergoing or have completed a medically assisted withdrawal, as well as for people with alcohol dependence who have managed to withdraw without medication but still need help with relapse prevention.

Acamprosate can be started before or during medically assisted withdrawal. Acamprosate is thought to have the potential to reduce toxicity and neuronal impairment during the withdrawal process, although this is not clearly established (Kalk and Lingford-Hughes, 2014). Prescribing acamprosate before completing withdrawal ensures that the person can benefit in the vulnerable period when medication to manage withdrawal symptoms has finished. This prescribing is outside the summary of product characteristics (SPC), but it is common practice and it is supported by clinical consensus of the alcohol guidelines development group. The Royal Pharmaceutical Society provides an overview of SPC.

Baseline investigations and monitoring

You should determine the person’s body weight before prescribing, because a lower dose schedule is used for adults who weigh under 60kg.

Baseline blood tests should include hepatic and renal function. Acamprosate is predominantly excreted by the kidneys. The manufacturers recommend it should not be prescribed in “cases of renal insufficiency” and state this is indicated with a serum creatinine level of more than 120 micromoles per litre, based on a 1994 report. Clinical judgement may also be supported by measuring a person’s estimated glomerular filtration rate (eGFR) (see dose schedule below).

The safety of acamprosate has not been established in patients with severe liver insufficiency. So, the manufacturers recommend caution in its use for this group. You should not give acamprosate to people with severe hepatic impairment, but you can give it to people with mild to moderate hepatic impairment if there is ongoing monitoring.

For people with acceptable baseline blood test results, repeated blood test monitoring is not essential. Although it may be helpful in treatment generally to provide feedback on a person’s improvement (for example, if liver enzymes were elevated at baseline but have since come down).

Dose schedule

Appropriate doses are 666mg (2 tablets), 3 times daily, for adults whose weight is 60kg and over. Adults under 60kg are advised to take a total of 1,332mg daily in divided doses (for example, 2 tablets (666mg) in the morning, one tablet (333mg) in the afternoon and one (333mg) more in the evening).

You should prescribe for people with mild to moderate renal impairment with caution (Ashley and Dunleavy, 2019) and in consultation with the BNF guidance on prescribing in renal impairment.

Suggested dose schedule in renal impairment

Guidance from the renal drug handbook (Ashley and Dunleavy, 2019) recommends that acamprosate can be considered for prescribing in renal impairment at the following doses:

eGFR 30 to 50 millilitres per minute - 333mg 3 times a day
eGFR 10 to 30 millilitres per minute - 333mg twice daily
eGFR below 10 millilitres per minute - 333mg once daily

Prescribing in renal impairment should be a shared decision with the patient and other professionals, such as the specialist renal team if applicable. Prescribing in patients with a creatinine level greater than 120 micromoles per litre, remains a contraindication based on the SPC. Naltrexone is an alternative option.

Prescribing arrangements

You can prescribe acamprosate in community alcohol treatment services, primary care, or hospital. When a person starts being prescribed acamprosate in community alcohol treatment services or hospital, it is generally in their best interests that prescribing is transferred to primary care when possible. This allows them to move on from specialist services while continuing to benefit from the medication.

There is no specific time limit on prescribing acamprosate, but a common approach is to prescribe for 6 months, with an extension to 12 months for people who experience ongoing benefit.

You should consider stopping prescribing acamprosate after 4 to 6 weeks if the person is continuing to drink alcohol and has experienced no reduction in drinking days and alcohol consumption.

Naltrexone

This section on naltrexone covers:

indications
baseline investigations and monitoring
dose schedule
prescribing arrangements

Indications

Naltrexone is a non-selective opioid antagonist that reduces the rewarding effect of alcohol and therefore the motivation to drink alcohol. Several meta-analyses and systematic reviews have concluded that naltrexone reduces a person’s return to heavy drinking, by reducing the risk that a lapse progresses to a full relapse (NICE, 2011).

Naltrexone is a first-line treatment for relapse prevention and you should consider it as an option for people who are undergoing or have completed a medically assisted withdrawal. You should also consider it for people with alcohol dependence who have managed to withdraw without medication but who need help with relapse prevention.

Specific considerations

Naltrexone is an opioid-receptor antagonist, so you should not prescribe it for people who:

are prescribed opioid medication
use non-prescribed opioids regularly or intermittently
are likely to need opioid medication

Naltrexone administered to opioid-dependent people can cause life-threatening withdrawal symptoms. If you suspect a patient of using or being dependent on opioids, you should establish that they have not taken any opioids for 7 to 10 days before starting naltrexone treatment.

Baseline investigations and monitoring

Baseline blood tests should include hepatic and renal function. Repeat blood tests are not needed for everyone but are advised for:

older people
people with co-occurring health conditions, including obesity
feedback on improvement of physical health, where that would be useful

You should not prescribe naltrexone for people with severe or acute hepatic impairment, acute hepatitis, or liver failure.

You can prescribe naltrexone for people with mild to moderate hepatic impairment with ongoing monitoring.

Dose schedule

The typical dose is 25mg as an initial dose increasing to 50mg daily. The 25mg dose is off-label. You should refer to MHRA guidance ‘Off-label or unlicensed use of medicines: prescribers’ responsibilities’ (see section 1.2). Prescribers should also refer to the SPC.

Prescribing arrangements

You can prescribe naltrexone in community alcohol treatment services, primary care or hospitals. When a person starts being prescribed naltrexone in community alcohol treatment services or hospitals, it is generally in their best interest that prescribing is transferred to primary care when possible because this allows them to move on from specialist services while continuing to benefit from the medication.

There is no specific time limit on prescribing naltrexone, but a common approach is to prescribe for 6 months, with an extension to 12 months for people who experience ongoing benefit.

You should stop prescribing naltrexone after 4 to 6 weeks if the person is continuing to drink alcohol and has experienced no benefit.

Choosing between acamprosate or naltrexone as first-line treatment

There are currently no clear indicators of which people respond best to which first-line treatments. Some studies (including Mann and others, 2018) have been based on the proposed mechanisms of action of the 2 drugs.

Based on these studies, acamprosate is likely to be of more benefit for people motivated by the ‘relief’ effects of alcohol (such as easing anxiety) by operating on the upregulated glutamatergic system (brain functions) found in alcohol dependence.

Naltrexone is more likely to benefit people whose alcohol use is mainly motivated by seeking the ‘positive reward’ effects of alcohol (since naltrexone blunts these effects) and so, a person who has a history of recurrent lapses (unrelated to anxiety) may be more likely to benefit from naltrexone.

Precision in choice of medication remains an area for further investigation to identify clear predictors of effectiveness.

In practice, the choice between acamprosate and naltrexone as first-line treatment is likely to be shaped by factors such as:

the person’s previous experience and preference
medical factors, such as the person’s renal or liver function or concurrent opioid use
practical details, such as the person’s preference for 3 times daily or once daily dosing

10.5.3 Second-line pharmacological interventions

Disulfiram

This section on disulfiram covers:

indications
baseline investigations and monitoring
dose schedule
prescribing arrangements

Indications

Disulfiram is usually a second-line treatment for people with moderate or severe alcohol dependence who have successfully completed withdrawal and want to maintain abstinence. NICE CG115 recommends that it should be considered for people who:

have a goal of abstinence but for whom acamprosate and naltrexone are not suitable
prefer disulfiram and understand the rationale and relative risks of taking the drug

Disulfiram acts by blocking aldehyde dehydrogenase (an enzyme), causing accumulation of aldehyde if a person drinks alcohol. This results in adverse effects including nausea, flushing and palpitations. So, it acts as a deterrent to alcohol use. The patient must not start disulfiram until 24 hours after they consumed their last alcoholic drink. Patients (and where relevant their families) must be warned that a disulfiram-alcohol reaction is potentially dangerous.

It’s very important that you inform the patient about the adverse consequences from disulfiram of taking even small amounts of alcohol. This involves informing them about the effects and about what food, drink and other products to avoid, including ingesting alcohol accidentally in food products or even from absorbing alcohol on the skin from cosmetic products. You should also inform the person that there is a potential for a reaction with alcohol up to 14 days after stopping disulfiram.

You should warn patients, and their families and carers, about the rare complication of liver damage, which can have rapid onset and be unpredictable. You should also advise patients that if they feel unwell or develop a fever or jaundice, they should stop taking disulfiram and seek urgent medical attention.

There are several medical conditions for which disulfiram should be prescribed with caution or is even contraindicated. These include:

hypertension
ischaemic heart disease
stroke

Disulfiram is contraindicated in psychosis and severe personality disorder and where there is risk of suicide (see SPC and BNF).

Prescribers should ensure they have access to the patient’s full medical history, and they should check on drug interactions, cautions and contraindications to prescribing in the SPC.

Where possible, clinicians should advise that a supportive family member or appropriate support person witnesses the doses. This has been shown to enhance the medication’s effectiveness by helping the patient adhere to the regimen.

Baseline investigations and monitoring

Baseline blood tests should include hepatic and renal function. Ongoing blood test monitoring should be guided by the results of baseline tests and the medical history.

Dose schedules

In the UK, the usual dose of disulfiram is 200mg daily, though higher doses are sometimes used for people who do not experience adverse effects with alcohol at this dose.

In the SPC, there is an example of an initial loading dose regimen with higher doses being given in the first few days. However, it is common and acceptable to start on 200mg daily without an initial loading regimen.

Prescribing arrangements

You can prescribe disulfiram in community alcohol treatment services, primary care, or hospitals. It is usual for disulfiram to be started and initially monitored by specialist alcohol treatment services. When a person starts being prescribed disulfiram in community alcohol treatment services or in hospital, they should be transferred to primary care prescribing, when possible, because this allows them to move on from specialist services while continuing to benefit from the medication.

Prescribers should review the person at least every 2 weeks for the first 2 months, then monthly for the following 4 months.

There is no specific time limit on prescribing but for subsequent, longer term prescription, monitoring at least 6-monthly is recommended by the guidelines development group.

Baclofen

This section on baclofen covers:

indications
baseline investigations and monitoring
dose schedule
prescribing arrangements

Use of baclofen in the UK

Baclofen is a GABA-B agonist that is licensed for other uses in the UK. It is not included in NICE CG115.

Several studies have evaluated its use to support abstinence from alcohol since the NICE clinical guideline was published and there has been an international consensus statement on its use (Agabio and others, 2019).

Baclofen is included in this guideline, although you should be clear that its use in the UK for the treatment of alcohol use disorders would be off-label. You should refer to MHRA guidance ‘Off-label or unlicensed use of medicines: prescribers’ responsibilities’ (see section 1.2). Prescribers should also refer to the SPC.

Indications

You should not use baclofen for patients who are still drinking alcohol or for managing alcohol withdrawal.

You should also avoid using baclofen where there is a risk of:

psychotic disorders
significant mood disorders, including hypomanic and manic episodes
current or past suicidal ideation or attempts (see SPC and BNF) (Sinclair and others, 2016; Agabio and others, 2018)

You can consider baclofen as a second line treatment for relapse prevention following successful withdrawal from alcohol for people who have:

not responded to first-line treatments (acamprosate or naltrexone)
contraindications to prescribing first-line medications, for example those who have advanced liver disease

The SPC also states that cases of misuse, abuse and dependence have been reported with baclofen. You should exercise caution when prescribing baclofen to patients with a history of substance use and they should be monitored for symptoms of baclofen misuse, abuse, or dependence. For example, this includes cases of dose escalation, drug-seeking behaviour or a development of tolerance.

You should prescribe baclofen with caution in people with co-occurring health conditions, particularly:

epilepsy (effect on seizure threshold)
mood disorder (risk of manic or hypomanic episodes)
current suicidal ideation or a history of suicide attempts (risk of intentional overdose)

Baseline investigations and monitoring

Baseline blood tests should include hepatic and renal function. Clinicians should refer to the SPC. However, you can prescribe baclofen with caution for people with hepatic or renal impairment.

You do not need to repeat blood test monitoring for everyone, but you should be guided by the patient’s medical history.

You must monitor liver enzymes in patients with hepatic impairment. You may need to adjust dosing for people with renal impairment.

Dose schedules

Research shows very wide variations in the size of the dose of baclofen, but we do not recommend using high doses. Clinical consensus of the guidelines development group is that baclofen should:

be started at a low dose and slowly titrated, with a typical maximum of 60mg daily
not be stopped abruptly, but slowly reduced (for example, reduce the total daily dose by 5mg each week) to avoid withdrawal symptoms

Prescribing arrangements

Baclofen should only be prescribed by a specialist clinician who takes responsibility for the ongoing monitoring of the patient.

10.5.4 Other drugs used for relapse prevention

Other drugs that are used for relapse prevention in alcohol use disorders include:

topiramate
gabapentin
sodium oxybate

While these drugs are used elsewhere in the world, they are not routinely used in the UK due to the lack of evidence.

10.5.5 Drugs that should not be used for relapse prevention

Antidepressant medication

Many people seeking help for alcohol use disorders have already been prescribed antidepressant medication. This may be appropriate if you are clear that the purpose of the prescription is to treat a pre-existing or co-occurring depressive disorder, but there is no role for antidepressant medication specifically to treat an alcohol use disorder. You should not prescribe antidepressant drugs (including selective serotonin reuptake inhibitors) with the purpose of preventing relapse in alcohol use disorders.

Benzodiazepines and z-drugs

You should not start prescribing benzodiazepines or z-drugs (sleeping tablets with effects similar to benzodiazepines, such as zopiclone or zolpidem) or continue them after managing withdrawal, with the goal of relapse prevention or promoting abstinence from alcohol.

For some people, it may still be appropriate to use these drugs for their standard recommended uses, such as for the short-term management of anxiety or insomnia.

10.5.6 Pharmacological intervention to reduce alcohol use: nalmefene

Use of nalmefene in the UK

Nalmefene is an opioid receptor antagonist at mu and delta subtypes and partial agonist at kappa subtype. In 2014, NICE published a technology appraisal on nalmefene.

Nalmefene is indicated for the reduction of alcohol consumption in adult patients with alcohol dependence who are likely to continue to drink, who do not experience physical withdrawal symptoms and who would not require detoxification.

You should only start prescribing nalmefene for patients who continue to have a high drinking risk level 2 weeks after initial assessment and it should be prescribed alongside psychosocial interventions.

Indications

Nalmefene is not suitable for people with moderate or severe alcohol dependence or who are non-dependent drinkers.

The target group for this pharmacological intervention is people with mild dependence, without complications, whose aim is to continue to drink alcohol at a reduced level and who are prepared to engage in concurrent psychosocial interventions.

Psychosocial interventions are the mainstay of treatment for this defined group, and most people will not require a pharmacological intervention. However, you can consider prescribing nalmefene for people in this group for whom a psychosocial intervention alone is not proving adequate. You should ask the patient to record their alcohol consumption for at least 2 weeks before deciding to start nalmefene.

If you do prescribe nalmefene, you should only do so alongside psychosocial interventions in specialist alcohol treatment services or a primary care setting.

Specific considerations

As nalmefene is an antagonist and partial agonist, you should not prescribe it for people who take opioid medication, use non-prescribed opioids either regularly or intermittently, or for those who are likely to need opioid medication. You should not prescribe nalmefene for people who:

have a current or recent opioid dependence
are in opioid withdrawal
have a recent history of acute alcohol withdrawal syndrome

Baseline investigations and monitoring

Baseline blood tests should include hepatic and renal function. You should avoid prescribing nalmefene to people with severe hepatic or renal impairment and prescribe it with caution to people with mild to moderate hepatic impairment.

Repeated blood test monitoring is not essential though it may be helpful in treatment overall, for feedback to the person on improvement in their health.

10.6 Pharmacological interventions for specific groups of people

This section provides guidance for specific groups. You should read this guidance along with:

general information on prescribing for withdrawal (in sections 10.3.1 to 10.3.7 in this chapter)
thiamine supplementation (in sections 10.4.2 and 10.4.3 in this chapter)
relapse prevention (section 10.5 in this chapter)

10.6.1 Pharmacological treatments for people using alcohol and other drugs or medications

People who use drugs and who are dependent on alcohol should be offered alcohol treatment interventions, including support for alcohol reduction and cessation either in the community or as an inpatient. You should follow this up with psychological and pharmacological interventions to prevent relapse.

You can find detailed guidance on addressing problem alcohol use with people who are in treatment for drug dependence in section 6.5 of Drug misuse and dependence: UK guidelines on clinical management.

Co-occurring alcohol and opioid dependence

Alcohol dependence is a common co-occurring condition in people with opioid dependence, and people with this combination of conditions are at high risk of death from the combined sedative effects of opioids and alcohol in overdose, as explained in NICE CG115. Treatment for both conditions should be integrated so they are managed together.

The UK drug treatment clinical guidelines are clear that optimising medication for opioid dependence is important. Some people will wish to undergo medically assisted withdrawal from alcohol while maintaining stable opioid substitution treatment (OST). This may be because they want to stop drinking alcohol but also want to continue to benefit from ongoing OST. Or they may want to withdraw from both alcohol and opioid drugs in due course but want to deal with alcohol first.

Management of withdrawal from alcohol for people with opioid dependence

When planning medically assisted withdrawal, clinicians should consider the degree of supervision required for its safe management alongside OST. Some people will need inpatient services or intensive community support such as day-patient supervision. This decision needs to be based on the factors that are considered for all people undergoing medically assisted withdrawal from alcohol, together with any additional factors related to their opioid use.

The UK drug treatment clinical guidelines recommend that when a person wants to withdraw from both alcohol and opioid drugs, you should aim to stabilise them on OST and then plan assisted withdrawal from alcohol, particularly if they are going to be managed in a community setting. Simultaneous withdrawal from both alcohol and opioid drugs is challenging and is best managed in an inpatient setting.

There is MHRA safety information on concurrent use of benzodiazepines and opioids.

Medication for relapse prevention

You should not prescribe naltrexone for people with ongoing opioid dependence or those who use opioid drugs intermittently. Because naltrexone is an opioid antagonist, you can prescribe it to support a patient to maintain their abstinence from opioid drugs (after their abstinence is clearly established), as recommended by the NICE technology appraisal guidance Naltrexone for the management of opioid dependence.

For people who have achieved abstinence from both alcohol and opioid drugs, and want to maintain this, you can prescribe naltrexone as long as there are no other contraindications, with the aim of supporting abstinence from both.

There is a lack of studies looking at the effectiveness of acamprosate in people who are also dependent on opioids. However, given its safety and tolerability, there is no reason acamprosate should not be used to support abstinence from alcohol, following medical assessment and the guidance on prescribing acamprosate (see section 10.5.2 on acamprosate above).

There is also a lack of studies of the use of disulfiram to support abstinence from alcohol in people dependent on opioids. If you are considering using disulfiram, you need to carry out a medical assessment and follow the guidance on prescribing disulfiram (see section 10.5.3 on disulfiram above).

Baclofen has potential to cause sedation if it is given alongside opioid medication such as methadone or buprenorphine, so should be used with caution.

Nalmefene is an opioid antagonist and should not be prescribed for people who are using prescribed or unprescribed opioid drugs (see section 10.5.6 on nalmefene above).

Co-occurring alcohol and cocaine use

This section covers management of alcohol withdrawal and relapse prevention for people who also use cocaine.

Management of withdrawal from alcohol

If a person takes cocaine with alcohol, some effects (including euphoria and increased heart rate) may be enhanced compared to using either substance alone. Long term concurrent cocaine and alcohol use can increase the risk of heart attacks and strokes. You should offer support and treatment to people with alcohol dependence who also use cocaine, to help them achieve abstinence from alcohol, whether or not they intend to stop using cocaine. When planning medically assisted withdrawal, you must consider the degree of supervision required for its safe management. If a person is unlikely to be able to stop using cocaine during the period of withdrawal from alcohol, there is a potential for problematic increases in blood pressure and heart rate during withdrawal. This means some people will need inpatient services or intensive community support.

Medication for relapse prevention

There have been a small number of studies of the potential effect of acamprosate to support abstinence from cocaine, and while the findings are inconclusive, acamprosate has been well-tolerated (Kampman and others, 2011). It is appropriate to offer acamprosate to support abstinence from alcohol in people who use cocaine (see the considerations described in section 10.5.2 on acamprosate above).

There have been several trials of naltrexone and disulfiram in people with co-occurring problem alcohol and cocaine use. For naltrexone, it is so far unclear whether this is effective, but there is a possible association between disulfiram and abstinence from both alcohol and cocaine (Pettinati and others, 2008).

You can offer either naltrexone or disulfiram to support abstinence from alcohol in people who also use cocaine, based on their medical history and current health, as well as their choice (see section 10.5.2 on naltrexone and section 10.5.3 on disulfiram for cautions and contraindications).

Co-occurring alcohol and benzodiazepine dependence

This section covers management of withdrawal and relapse prevention medication for people with co-occurring benzodiazepine dependence.

Management of withdrawal

Concurrent use of a prescribed benzodiazepine or z-drug (such as zopiclone or zolpidem) is common in patients with alcohol dependence. These drugs are often prescribed in primary care or initiated by mental health services.

If you need to plan concurrent withdrawal from both alcohol and benzodiazepines, you should consider managing the person in an inpatient setting. This is because the dose of benzodiazepine medication used for withdrawal will need to be higher. You should base their initial daily dose on the requirements for alcohol withdrawal plus the equivalent regularly used daily dose of benzodiazepine. When the person has been using unprescribed benzodiazepines, this is difficult to assess and they are likely to need an inpatient setting.

Withdrawal is best managed with one benzodiazepine (chlordiazepoxide or diazepam) rather than multiple benzodiazepines. Concurrent withdrawal from alcohol and benzodiazepines will take longer than withdrawal from alcohol alone, so you should plan inpatient admissions for 2 to 3 weeks or longer, depending on the severity of co-occurring benzodiazepine dependence.

Concurrent withdrawal from alcohol and benzodiazepines is best managed in an inpatient setting. If withdrawal is managed in the community, the regimen may need to last for several weeks, depending on the person’s symptoms and discomfort, as recommended by NICE CG115. It will also be necessary to involve specialist clinicians with knowledge and competencies in managing withdrawal for people with co-occurring alcohol and benzodiazepine dependence.

Some people requiring medically assisted withdrawal from alcohol are already receiving a prescription for a stable regular daily dose of a benzodiazepine or z-drug, possibly for another indication. They may not want any change to this prescribed medication while they undertake alcohol withdrawal. In these circumstances, the regular medication can be maintained as a baseline while they undergo withdrawal from alcohol, with a planned reducing regimen of chlordiazepoxide or diazepam. The person may then decide (at a later date) on a plan to reduce and stop the regularly prescribed medication.

As for all medically assisted withdrawal from alcohol, you should consider the degree of supervision required for its safe management alongside use of current medication.

Medication for relapse prevention

You can offer pharmacological interventions for preventing relapse to alcohol use to people who have benzodiazepine dependence. If you do this, the same considerations as for all people will apply. However, you should note that for people who continue to take benzodiazepine medication, increased sedation can occur if they take baclofen, which should be considered when prescribing baclofen.

10.6.2 Prescribing for older people

You should read this section with section 25.8 on older people in chapter 25 on developing inclusive services.

Screening older people

There is an increasing prevalence of problem alcohol use in older populations (people aged 65 years and over). Routine screening for alcohol use risk among older people should be part of any ongoing comprehensive assessment in any health or social setting (RCPsych, 2018).

Issues to consider when prescribing for older people

Older adults are more likely to:

have other mental health conditions
have other physical health conditions
be taking other medication

You will therefore need to make appropriate dose adjustments for age-related pharmacokinetic and pharmacodynamic changes and carry out regular monitoring (Butt and others, 2020; Lingford-Hughes and others, 2012; Haber and others, 2009). But this should not be a deterrent to using medication, as it can play a crucial role in treatment and recovery and you should always consider using it. Refer to BNF guidance on prescribing in the elderly.

Pharmacological management of withdrawal for older people

NICE CG115 recommends that benzodiazepines remain the treatment of choice for managing withdrawal in older people, alongside nutritional supplements. See section 10.3 in this chapter on prescribing medication for managing withdrawal from alcohol. However, you can consider prescribing a shorter-acting benzodiazepine, such as oxazepam (off-label), where you have concerns about accumulation and subsequent over-sedation.

Clinicians are less likely to be familiar with such shorter-acting benzodiazepines compared with other benzodiazepines that are more commonly used, such as chlordiazepoxide or diazepam. So, it may be preferable to use familiar benzodiazepines with careful titration and choice of dose. Given the patient is likely to have co-occurring physical health conditions and be at risk of nutritional deficiencies, it is essential to assess them for potential complications, and for Wernicke’s encephalopathy, as well as continuing to monitor them during withdrawal. So, you need to consider whether a community or inpatient setting is most suitable for withdrawal. See section 10.4.3 on preventing and managing Wernicke’s encephalopathy.

Pharmacological management of relapse prevention for older people

There is limited evidence about the efficacy and safety of prescribing relapse prevention medication in this population. If we assume that treating older people with relapse prevention medication has similar results to the working age adult population, you can consider using it for older people with moderate to severe alcohol dependence if you think that the benefits outweigh the risks for an individual (Butt and others, 2020; Lingford-Hughes and others, 2012; NICE, 2011).

When using naltrexone in older people, you should monitor their liver function tests before and during medically assisted withdrawal and at 3 months and 6 months afterwards.

Acamprosate may require dose adjustment due to age-related kidney disease. Using acamprosate in people aged 65 and over is off-label due to lack of evidence on its use in that age group (see SPC and baseline blood tests and monitoring for acamprosate in section 10.5.2 in this chapter).

Disulfiram is less likely to be appropriate to use, due to the number of contraindications and cautions that apply to older adults.

10.6.3 Prescribing for young people

There are specific considerations when prescribing for young people. You should read this section along with section 23.14 in chapter 23 on specialist alcohol interventions and support for children and young people, and the British National Formulary for Children.

NICE CG115 covers young people aged 10 years and older and includes a specific pathway for 10 to17 year-olds. For those young people who require medically assisted withdrawal, you can use benzodiazepines (chlordiazepoxide or diazepam) with doses adjusted based on their:

age
height
weight

Consider inpatient admission in an age-appropriate setting with access to specialist alcohol treatment expertise. Children and young people should not be treated in an adult setting.

There is limited evidence from trials investigating the efficacy or use of relapse prevention medications in young people. Also, relapse prevention medications are not licensed for use in people aged 17 and under because of the lack of evidence to guide their use and safety in younger people. There are some pilot placebo-controlled or open-label randomised control trials of acamprosate, naltrexone or disulfiram in young people (mainly 15 to 19 years old). But all the studies are based on small groups and their results should be interpreted very cautiously (Clark, 2012).

NICE CG115 recommends that after a careful review of the risks and benefits, specialist clinicians can consider offering acamprosate or oral naltrexone, along with cognitive behavioural therapy, to young people over 16 who have not benefited from or engaged with a multicomponent treatment programme.

This would be an off-label use of oral naltrexone and acamprosate. See section 10.2.2 on unlicensed or off-label prescribing.

10.6.4 Women and those who are pregnant or breastfeeding

Alcohol use during pregnancy

This section focuses on alcohol treatment prescribing interventions for women and those who are pregnant or breastfeeding. There is guidance on other aspects of treatment and support during pregnancy and the perinatal period, and on fetal alcohol spectrum disorder in chapter 24 on pregnancy and perinatal care.

Psychosocial interventions are the mainstay of managing problem alcohol use during pregnancy, though evidence comes primarily from experience rather than clinical trials.

Many patients who continue to drink excessively in pregnancy are likely to have several co-occurring conditions including mental health disorders. Some will also smoke tobacco or use other substances, so comprehensive assessment for alcohol treatment by an experienced clinician is crucial (McAllister-Williams and others, 2017).

It is essential that all services involved with the patient during pregnancy and in the perinatal period work together to co-ordinate care and share information appropriately. This will include joint multidisciplinary and multi-agency assessment, and care-planning, including safeguarding, maternity services and other relevant services such as mental health or domestic abuse services (NICE, 2010).

If a patient is undergoing medically assisted withdrawal while pregnant or in the perinatal period, child safeguarding services should normally be involved. The clinicians and staff involved with the patient must follow national guidance (see annex 1 on legislation and statutory guidance) and their service procedures on child safeguarding.

See section 24.7.4 in chapter 24 on pregnancy and perinatal care for further guidance on safeguarding in pregnancy. And see section 24.9.1 in chapter 24 on pregnancy and perinatal care for further guidance on multi-agency assessment and multi-agency care-planning.

Pharmacological management of withdrawal in pregnancy

For patients who require medically assisted withdrawal during pregnancy, you can use chlordiazepoxide. You should consider if it’s best to do this as an inpatient with the antenatal team, so that they can appropriately monitor the patient and the fetus.

Risks and benefits of treatment should be discussed with the patient.

Chlordiazepoxide and possible risk of genotoxicity (damage to genetic information)

Chlordiazepoxide should not be used during pregnancy, especially during the first and last trimester unless the clinical condition of the woman requires treatment with chlordiazepoxide. You can find the available evidence on the safety of chlordiazepoxide in the summary of product characteristics for Librium 5mg capsules.

The change is the result of new EMA guidance, rather than new evidence for the genotoxicity of chlordiazepoxide.

You should not use carbamazepine in pregnancy for safety reasons.

There is an MHRA drug safety update about using antiepileptic drugs in pregnancy.

Patients undergoing medically assisted withdrawal during pregnancy will need thiamine supplementation as described in section 10.4.3 on preventing and managing WE. Pregnant patients should also take folic acid supplements as advised in the NICE public health guideline Maternal and child nutrition. Patients should follow advice from the GP and specialist midwife on other aspects of nutritional support.

You can undertake medically assisted withdrawal with patients in any trimester, though if it’s close to their delivery, you must consider the impact of withdrawal from alcohol or benzodiazepines on the baby. The baby will need specialist paediatric monitoring if it is born during the medically assisted withdrawal. Any enduring alcohol withdrawal in the parent should be appropriately treated. The baby should be assessed and then assessed again regularly throughout infancy for fetal alcohol spectrum disorder.

Section 24.8.3 in chapter 24 on pregnancy and perinatal care provides more guidance on caring for the new-born baby with prenatal alcohol exposure.

Relapse prevention during pregnancy

Abstinence from alcohol is strongly recommended in pregnancy. The UK chief medical officers’ low-risk drinking guidelines advise that the safest approach is to avoid drinking any alcohol during pregnancy. Due to lack of safety data, relapse prevention medication cannot be routinely recommended.

The BNF advises that acamprosate and naltrexone should be avoided during pregnancy unless the potential benefit outweighs risk. But alcohol is a known human teratogen and treatment may be considered in individual cases, based on the balance of risk and discussion with the patient. Women and those who become pregnant while taking acamprosate or naltrexone will generally be advised to stop taking these.

You should avoid using disulfiram during pregnancy due to potential teratogenic effects of acetaldehyde.

The BNF for baclofen states that the manufacturer advises using it in pregnancy only if the potential benefit outweighs risk (as it was found to produce toxicity in animal studies).

The BNF for nalmefene states that the manufacturer advises to avoid its use during pregnancy (as it was found to produce toxicity in animal studies).

For up-to-date information on medication in pregnancy, you can visit the UK teratology information service.

Pharmacological management of withdrawal for patients who are breastfeeding

In general, the health benefits of breastfeeding mean that it should be encouraged whenever possible. When a breastfeeding woman consumes alcohol, it is readily transferred into breast milk. The amount received by the baby will depend on the timing of feeding related to when the alcohol was consumed. Alcohol is likely to cause lethargy, drowsiness and poor feeding in babies. It also presents a risk of hypoglycaemia. So, you should strongly recommend that breastfeeding patients do not consume alcohol.

Alcohol treatment services should prioritise women and those with alcohol dependence and have babies, including those who are breastfeeding, for rapid assessment for and provision of medically assisted withdrawal.

There is a lack of well-conducted studies to guide how you provide advice about breastfeeding in the context of prescribed medication. You should get specialist advice when planning and providing individually tailored pharmacological interventions for women who are breastfeeding. Useful sources of specialist advice include the Breastfeeding network and the Specialist Pharmacy Service safety in breastfeeding guidance.

Clinicians should discuss the risks and benefits of medically assisted withdrawal when breastfeeding with the patient so a shared decision about treatment can be made. However, clinicians should recommend that the patient stop breastfeeding while taking the medication to avoid adverse effects in the baby if the medication is transferred in the breast milk. This may be particularly relevant if large doses of benzodiazepines are used during the medically assisted withdrawal.

There should be a multidisciplinary approach to supporting the mother and baby and this should include input from neonatal paediatricians and specialist breastfeeding advice and support for the mother. The mother can be supported to express milk during the medically assisted withdrawal, to increase the chance that she can continue to lactate and resume breastfeeding after the medically assisted withdrawal has finished.

Patients may vary in their approach to risk. If the patient makes a fully informed choice not to stop breastfeeding, the clinician should seek specialist advice on the relative risks and benefits and any actions they can take to mitigate risks associated with breastfeeding during medically assisted withdrawal.

Relapse prevention during breastfeeding

Psychological approaches and social support are the mainstay of relapse prevention for women who want to start or continue breastfeeding.

You should discuss the risks and benefits of relapse prevention medication with the patient so a shared decision can be made. However, due to the lack of comprehensive evidence available, you should routinely recommend that women and those who are breastfeeding should avoid pharmacological treatment to prevent relapse using medications such as acamprosate, naltrexone and disulfiram.

The lack of studies looking at long-term outcomes after taking relapse prevention medication during breastfeeding introduces a degree of uncertainty and patients may vary in their approach to risk. In exceptional circumstances you might want to consider prescribing relapse prevention medication, if the patient has requested this based on a fully informed understanding of risks and benefits.

If you are considering treatment, you should undertake comprehensive assessment of risk for each individual patient who is breastfeeding. You should also get individualised specialist advice on prescribing relapse prevention medication for the patient who is breastfeeding (see section above on pharmacological management of withdrawal for useful sources of specialist advice on prescribing and breastfeeding). Pharmacological principles suggest using the lowest possible effective dose, for the shortest time. For example, this might only be during periods of a particularly high risk of relapse. You should not consider pharmacological treatment as a single option without accompanying psychological support or interventions to help reduce risk of relapse.

Due to the lack of information on safety, you should avoid prescribing disulfiram. If considering prescribing relapse prevention medication in exceptional circumstances, you should consider alternatives (acamprosate or naltrexone).

10.6.5 Prescribing for people with co-occurring mental health conditions

Many people with problem alcohol use have co-occurring mental health conditions or their symptoms. When you are considering treatment with medication you should do a comprehensive assessment with the patient to understand the relationship between their alcohol use and any other mental health symptoms or conditions.

Evidence shows that you should treat both their problem alcohol use and their mental health condition in their own right as treating one does not necessarily lead to resolution of the other (Lingford-Hughes and others, 2012; Haber and others, 2009). There is no evidence that a treatment for a mental health condition is less effective when it is co-occurring with problem alcohol use, so treatment should follow usual clinical guidelines, for example NICE guidelines.

There is more guidance on other aspects of working with co-occurring mental health conditions in chapter 18 on co-occurring mental health conditions.

Pharmacological management of withdrawal for people with co-occurring mental health conditions

This section should be read with section 10.2.4 on setting for medically assisted withdrawal based on severity of dependence and complexity of need in this chapter.

When choosing a benzodiazepine in people with a co-occurring mental health condition, you can follow guidelines outlined in this chapter. However, you will need to check the BNF and SPC for interactions of medicines used for medically assisted withdrawal against an individual patient’s current medication.

Pharmacological management of relapse prevention for people with co-occurring mental health conditions

Abstinence, or at least a reduction in a person’s alcohol consumption, is important to improving their mental health symptoms and conditions. You should consider prescribing relapse prevention medication for people with moderate or severe alcohol dependence alongside psychosocial or psychological interventions (Lingford-Hughes and others, 2012; NICE, 2011; Barnes and others, 2020; Goodwin and others, 2016; Cleare and others, 2015).

Disulfiram is contraindicated in psychosis and severe personality disorder and where there is risk of suicide (see SPC and BNF).

You should also avoid using baclofen where there is a risk of:

psychotic disorders
significant mood disorders, including hypomanic and manic episodes
current or past suicidal ideation or attempts (see SPC and BNF) (Sinclair and others, 2016; Agabio and others, 2018)

Naltrexone has been the most studied and reviewed medication with evidence to support it improving alcohol dependence when co-occurring with a range of mental health conditions (Lingford-Hughes and others, 2012). This includes for:

depression
post-traumatic stress disorder
bipolar disorder

There is an association between problem alcohol use and depression, and antidepressant use among people with problem alcohol use is common. However, reviews of the evidence show that the effectiveness of antidepressant medication is reduced while people are drinking heavily. Study of the relationship between selective serotonin reuptake inhibitors (SSRIs) and alcohol use is an emerging field and, when prescribing these medications for patients with problem alcohol use, it is important to be aware of the most up to date evidence and carefully consider the risks and benefits. It remains important to offer medication such as acamprosate or naltrexone and monitor for efficacy (Agabio and others, 2018; Foulds and others, 2015; Iovenio and others, 2011; Nunes and Levin, 2004; Torrens and others, 2005).

See section 10.5.1 to 10.5.5 for guidance on prescribing for relapse prevention.

10.6.6 Prescribing for people with liver disease

There is no specific evidence on which to base the management of alcohol withdrawal in people with advanced alcohol-related liver disease (ARLD). People with decompensated cirrhosis (complicated by jaundice, ascites, variceal bleeding, renal impairment, sepsis or hepatic encephalopathy) and alcohol withdrawal can be challenging to manage. In these cases, you should seek advice from a healthcare professional with experience in the management of liver disease, hepatic encephalopathy and withdrawal, as recommended by NICE CG100.

Specific treatment considerations will depend on the severity of liver disease and the severity of withdrawal risk. People with advanced ARLD should be admitted to hospital for withdrawal.

In general, you can consider using a shorter-acting benzodiazepine in people with significantly compromised liver function, such as oxazepam or lorazepam. This includes jaundice (bilirubin of more than 80 micromoles per litre), coagulopathy (international normalised ratio (INR) of more than 1.5) and in particular, the presence of hepatic encephalopathy. You can use longer-acting benzodiazepines (for example chlordiazepoxide and diazepam) with the knowledge that people with compromised liver function will:

need less
metabolise slower
have greater accumulation (NICE, 2011)

Expertise available in the service, guidance and the quality and skill of monitoring is more important than the choice of benzodiazepine. You should take care not to over-sedate the person. If hepatic encephalopathy worsens, you should stop the benzodiazepine, and if it is needed later, you should prescribe it at a lower dose.

Abstinence from alcohol is a vital goal for people with ARLD since abstinence improves outcomes in all stages of the disease. There should be established care pathways between specialist liver services and alcohol treatment services. You can find examples of guidance on developing care pathways in guidance on alcohol treatment pathways and Scottish Health Action on Alcohol Problems good practice guidance for people with ARLD.

You should consider pharmacotherapy for relapse prevention for people with ARLD. However, many of the drugs available have not specifically been tested in people with advanced ARLD.

Of the relapse prevention drugs recommended by NICE CG115, disulfiram and naltrexone are metabolised in the liver, whereas acamprosate is not. You should avoid using disulfiram for people with advanced ARLD because of potential hepatotoxicity (Forns and others, 1994; EASL, 2018; Crabb and others, 2020). Naltrexone has not been studied systematically in people with advanced ARLD.

Acamprosate has a generally good safety profile and is not metabolised in the liver. While there is preliminary data suggesting safety in people with Childs’ A and B cirrhosis, there are no trials of repeatedly administering acamprosate in people with cirrhosis.

For people with advanced ARLD, using either disulfiram or naltrexone is not recommended (EASL, 2018; Crabb and others, 2020). Based on limited data, acamprosate is probably safe and may be used (Crabb and others, 2020).

In clinical practice, it is important to make the distinction between people with advanced ARLD and those with less severe liver disease. For the latter group, relapse prevention medication could be safely used with appropriate monitoring. People with advanced ARLD will have at least one of:

significant synthetic dysfunction (impaired ability to synthesise proteins), indicated by jaundice (bilirubin of more than 80 micromoles per litre)
coagulopathy (INR of more than 1.5)
hepatic encephalopathy (decline in brain function that occurs as a result of severe liver disease)

You should involve specialist hepatology services in diagnosis.

Baclofen is currently the only pharmacotherapy for alcohol use disorder for which there is randomised controlled trial data in people with cirrhosis (including those with decompensated cirrhosis but excluding hepatic encephalopathy) (Addolorato and others, 2007). Further confirmatory studies are required and there are still questions on optimal dosing and duration of treatment. However, it does appear that baclofen may be useful in people with ARLD cirrhosis and alcohol use disorder. Prescribing baclofen in such cases should be in consultation with a hepatology specialist.

Pharmacological interventions to reduce alcohol use in liver disease

As described earlier in this chapter, NICE recommends using nalmefene to reduce alcohol consumption in a defined group of people who have mild alcohol dependence with a high drinking risk level without physiological withdrawal symptoms. Nalmefene has not been tested in people who have ARLD cirrhosis, and for these people the goal should be abstinence rather than reduction. However, you can use nalmefene for people with earlier stage liver disease who can benefit from a reduction goal if abstinence is not feasible, provided they meet the criteria described in section 10.5.6 on nalmefene above.

10.7 Benzodiazepine withdrawal regimens

10.7.1 Overview

Individual needs, circumstances and setting

The following benzodiazepine withdrawal regimens are examples only, based on the clinical consensus of the alcohol guidelines development group. They are not protocols that must be followed.

Clinicians should make prescribing decisions based on individual needs, circumstances and setting.

The regimens suggested in this section are suitable for people with moderate dependence (15 to 30 units of alcohol per day and a SADQ score of 15 to 30) who undergo medically assisted withdrawal in the community or, where indicated, in inpatient settings. There are 3 suggested tiers of dosage for each drug. You should select the dosage based on the number of units the person drinks per day, the SADQ score within the range, and other clinical factors.

Adapting regimens

Although such regimens often work with no need for change, community staff will need experienced prescribers for support if regimens require adaptation (if doses need to be reduced or withheld). For people who show objective alcohol withdrawal symptoms and score high on alcohol withdrawal scales such as the Clinical Institute Withdrawal Assessment for Alcohol (revised version), the doses may need to be increased. These regimens include the option to provide an additional daily dose to be used PRN (if needed) based on telephone advice or in-person advice from the clinician monitoring the medically assisted withdrawal. This can be useful as it helps control symptoms, while allowing clinicians the time to adapt the regimen and supply the additional medication that the person will need.

Severe dependence

The example regimens in section 10.7.2 below are for treating people with moderate dependence. For people with severe dependence, they will likely need higher doses than are shown in these regimens to adequately control withdrawal, prescribed according to the SPC for the chosen medication. This should usually be managed in an inpatient setting with careful titration of dose and ongoing evaluation of the severity of withdrawal and appropriate interventions. In some circumstances, it may be possible to provide community medically assisted withdrawal in the community (see section 10.2.4).

Make sure the patient is adequately supervised if high doses are administered and gradually reduce the dose over 7 to 10 days to avoid alcohol withdrawal recurring. If you are considering offering community medically assisted withdrawal to someone with severe dependence, you should follow the guidance on individual assessment of benefits and risks of the setting for the person in sections 11.5.5 and 11.7.2 in chapter 11 on community medically assisted withdrawal.

The BNF contains a safety alert from the MHRA about prescribing benzodiazepines along with opioids.

10.7.2 Example regimens for planned, fixed-dose alcohol withdrawal (moderate dependence)

Chlordiazepoxide

Table 1: alcohol withdrawal regimen (moderate dependence) for chlordiazepoxide 5mg capsules

Start dose chlordiazepoxide 15mg QDS (4 times daily).

Day	8am (number of capsules to take)	12:30pm (number of capsules to take)	5pm (number of capsules to take)	10pm (number of capsules to take)	PRN (only to be taken if recommended by a doctor or nurse)	Total number of capsules to take per day (without PRN)	Total number of capsules to take per day (with PRN)
1	15mg (3)	15mg (3)	15mg (3)	15mg (3)	15mg (3)	12	15
2	10mg (2)	10mg (2)	10mg (2)	10mg (2)	10mg (2)	8	10
3	10mg (2)	Stop	10mg (2)	10mg (2)	10mg (2)	6	8
4	5mg (1)		5mg (1)	5mg (1)	5mg (1)	3	4
5	5mg (1)		Stop	5mg (1)	5mg (1)	2	3
6	Stop			5mg (1)	Stop	1	1
7				Stop		Stop	Stop

Table 2: alcohol withdrawal regimen (moderate dependence) for chlordiazepoxide 5mg capsules

Start dose chlordiazepoxide 20mg QDS (4 times daily).

Day	8am (number of capsules to take)	12:30pm (number of capsules to take)	5pm (number of capsules to take)	10pm (number of capsules to take)	PRN (only to be taken if recommended by a doctor or nurse)	Total number of capsules to take per day (without PRN)	Total number of capsules to take per day (with PRN)
1	20mg (4)	20mg (4)	20mg (4)	20mg (4)	20mg (4)	16	20
2	15mg (3)	15mg (3)	15mg (3)	15mg (3)	15mg (3)	12	15
3	10mg (2)	10mg (2)	10mg (2)	10mg (2)	10mg (2)	8	10
4	10mg (2)	Stop	10mg (2)	10mg (2)	10mg (2)	6	8
5	5mg (1)		5mg (1)	5mg (1)	5mg (1)	3	4
6	5mg (1)		Stop	5mg (1)	5mg (1)	2	3
7	Stop			5mg (1)	Stop	1	1
8				Stop		Stop	Stop

Table 3: alcohol withdrawal regimen (moderate dependence) for chlordiazepoxide 5mg capsules

Start dose chlordiazepoxide 25mg QDS (4 times daily).

Day	8am (number of capsules to take)	12:30pm (number of capsules to take)	5pm (number of capsules to take)	10pm (number of capsules to take)	PRN (only to be taken if recommended by a doctor or nurse)	Total number of capsules to take per day (without PRN)	Total number of capsules to take per day (with PRN)
1	25mg (5)	25mg (5)	25mg (5)	25mg (5)	25mg (5)	20	25
2	20mg (4)	20mg (4)	20mg (4)	20mg (4)	20mg (4)	16	20
3	15mg (3)	15mg (3)	15mg (3)	15mg (3)	15mg (3)	12	15
4	10mg (2)	10mg (2)	10mg (2)	10mg (2)	10mg (2)	8	10
5	10mg (2)	Stop	10mg (2)	10mg (2)	10mg (2)	6	8
6	5mg (1)		5mg (1)	5mg (1)	5mg (1)	3	4
7	5mg (1)		Stop	5mg (1)	5mg (1)	2	3
8	Stop			5mg (1)	Stop	1	1
9				Stop		Stop	Stop

Diazepam

Table 4: alcohol withdrawal regimen (moderate dependence) for diazepam 2mg tablets

Start dose diazepam 6mg QDS (4 times daily).

Day	8am (number of tablets to take)	12:30pm (number of tablets to take)	5pm (number of tablets to take)	10pm (number of tablets to take)	PRN (only to be taken if recommended by a doctor or nurse)	Total number of tablets to take per day (without PRN)	Total number of tablets to take per day (with PRN)
1	6mg (3)	6mg (3)	6mg (3)	6mg (3)	6mg (3)	12	15
2	4mg (2)	4mg (2)	4mg (2)	4mg (2)	4mg (2)	8	10
3	4mg (2)	Stop	4mg (2)	4mg (2)	4mg (2)	6	8
4	2mg (1)		2mg (1)	2mg (1)	2mg (1)	3	4
5	2mg (1)		Stop	2mg (1)	2mg (1)	2	3
6	Stop			2mg (1)	Stop	1	1
7				Stop		Stop	Stop

Table 5: alcohol withdrawal regimen (moderate dependence) for diazepam 2mg tablets

Start dose diazepam 8mg QDS (4 times daily).

Day	8am (number of tablets to take)	12:30pm (number of tablets to take)	5pm (number of tablets to take)	10pm (number of tablets to take)	PRN (only to be taken if recommended by a doctor or nurse)	Total number of tablets to take per day (without PRN)	Total number of tablets to take per day (with PRN)
1	8mg (4)	8mg (4)	8mg (4)	8mg (4)	8mg (4)	16	20
2	6mg (3)	6mg (3)	6mg (3)	6mg (3)	6mg (3)	12	15
3	4mg (2)	4mg (2)	4mg (2)	4mg (2)	4mg (2)	8	10
4	4mg (2)	Stop	4mg (2)	4mg (2)	4mg (2)	6	8
5	2mg (1)		2mg (1)	2mg (1)	2mg (1)	3	4
6	2mg (1)		Stop	2mg (1)	2mg (1)	2	3
7	Stop			2mg (1)	Stop	1	1
8				Stop		Stop	Stop

Table 6: alcohol withdrawal regimen (moderate dependence) for diazepam 2mg tablets

Start dose diazepam 10mg QDS (4 times daily).

Day	8am (number of tablets to take)	12:30pm (number of tablets to take)	5pm (number of tablets to take)	10pm (number of tablets to take)	PRN (only to be taken if recommended by a doctor or nurse)	Total number of tablets to take per day (without PRN)	Total number of tablets to take per day (with PRN)
1	10mg (5)	10mg (5)	10mg (5)	10mg (5)	10mg (5)	20	25
2	8mg (4)	8mg (4)	8mg (4)	8mg (4)	8mg (4)	16	20
3	6mg (3)	6mg (3)	6mg (3)	6mg (3)	6mg (3)	12	15
4	4mg (2)	4mg (2)	4mg (2)	4mg (2)	4mg (2)	8	10
5	4mg (2)	Stop	4mg (2)	4mg (2)	4mg (2)	6	8
6	2mg (1)		2mg (1)	2mg (1)	2mg (1)	3	4
7	2mg (1)		Stop	2mg (1)	2mg (1)	2	3
8	Stop			2mg (1)	Stop	1	1

10.8 References

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Agabio R, Sinclair JMA and Leggio L. The Cagliari statement on baclofen for the treatment of alcohol use disorder: an international consensus. French Journal of Psychiatry 2019: volume 1, supplement 2, page S28.

Agabio R, Trogu E and Pani PP. Antidepressants for the treatment of people with co-occurring depression and alcohol dependence. Cochrane Database of Systematic Reviews, 2018.

American Society of Addiction Medicine. Alcohol withdrawal management guideline. ASAM, 2020.

Ashley C and Dunleavy A (editors). The renal drug handbook: the ultimate prescribing guide for renal practitioners (fifth edition). Taylor and Francis Group, 2019.

Barnes T, Drake R, Paton C and others. Evidence-based guidelines for the pharmacological treatment of schizophrenia: updated recommendations from the British Association for Psychopharmacology. Journal of Psychopharmacology 2020: volume 34, issue 1, pages 3 to 78.

Butt PR, White-Campbell M, Canham S, Dowsett Johnston A, Indome EO, Purcell B, Tung J and Van Bussel L. Canadian guidelines on alcohol use disorder among older adults. Canadian Geriatrics Journal 2020: volume 23, issue 1, pages 143 to 148.

Clark D. Pharmacotherapy for adolescent alcohol use disorder. CNS Drugs 2012: volume 26, issue 7, pages 559 to 569.

Cleare A, Pariante C, Young A and others. Evidence-based guidelines for treating depressive disorders with antidepressants: a revision of the 2008 British Association for Psychopharmacology guidelines. Journal of Psychopharmacology 2015: volume 29, issue 5, pages 459 to 525.

Cook C, Hallwood P and Thomson A. B vitamin deficiency and neuropsychiatric syndromes in alcohol misuse. Alcohol and Alcoholism 1998: volume 33, issue 4, pages 317 to 336.

Crabb D, Im G, Szabo G, Mellinger J and Lucey M. Diagnosis and treatment of alcohol-associated liver diseases: 2019 practice guidance from the American Association for the Study of Liver Diseases. Hepatology 2020: volume 71, issue 1, pages 306 to 333.

European Association for the Study of the Liver (EASL). EASL clinical practice guidelines: management of alcohol-related liver disease. Journal of Hepatology 2018: volume 69, issue 1, pages 154 to 181.

Fix O, Hameed B, Fontana R, Kwok R, McGuire B Mulligan DC, Pratt D, Russo M, Schilsky M, Verna E, Loomba R and others. Clinical best practice advice for hepatology and liver transplant providers during the COVID‐19 pandemic: AASLD expert panel consensus statement. Hepatology 2020: volume 72, issue 1, pages 287 to 304.

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Foulds J, Adamson S, Boden J and others. Depression in patients with alcohol use disorders: systematic review and meta-analysis of outcomes for independent and substance-induced disorders. Journal of Affective Disorders 2015: volume 185, pages 47 to 59.

Goodwin G, Haddad P, Ferrier I and others. Evidence-based guidelines for treating bipolar disorder: revised third edition recommendations from the British Association for Psychopharmacology. Journal of Psychopharmacology 2016: volume 30, issue 6, pages 495 to 553.

Haber P, Lintzeris N, Proude E and Lopatko, O. Quick reference guide to the treatment of alcohol problems. Australian Government, Department of Health and Aged Care, 2009.

Heberlein A, Leggio L, Stichtenoth D and Hillemacher T. The treatment of alcohol and opioid dependence in pregnant women. Current Opinion in Psychiatry 2012: volume 25, issue 6, pages 559 to 564.

Iovenio N, Tedeschini E, Bentley K, Evins M and Papakostas G. Antidepressants for major depressive disorder and dysthymic disorder in patients with comorbid alcohol use disorders: a meta-analysis of placebo-controlled randomized trials. Journal of Clinical Psychiatry 2011: volume 72, issue 8, pages 1,144 to 1,151.

Kalk N and Lingford-Hughes A. The clinical pharmacology of acamprosate. British Journal of Clinical Pharmacology 2014: volume 77, issue 2, pages 315 to 323.

Kampman K, Dackis C, Pettinati H, Lynch K, Sparkman T and O’Brien C. A double-blind, placebo-controlled pilot trial of acamprosate for the treatment of cocaine dependence. Addictive Behaviors 2011: volume 36, issue 3, pages 217 to 221.

Lingford-Hughes AR, Welch S, Peters L and Nutt DJ. BAP updated guidelines: evidence-based guidelines for the pharmacological management of substance abuse, harmful use, addiction and comorbidity: recommendations from BAP. Journal of Psychopharmacology 2012: volume 26, issue 7, pages 899 to 952.

Mann K, Roos C, Hoffmann S and others. Precision medicine in alcohol dependence: a controlled trial testing pharmacotherapy response among reward and relief drinking phenotypes. Neuropsychopharmacology 2018: volume 43, pages 891 to 899.

Mayo-Smith M, Beecher L, Fischer T and others. Management of alcohol withdrawal delirium: an evidence-based practice guideline. Archives of Internal Medicine 2004: volume 164, issue 13, pages 1,405 to 1,412.

McAllister-Williams RH, Baldwin DS, Cantwell and others. British Association for Psychopharmacology consensus guidance on the use of psychotropic medication preconception, in pregnancy and postpartum 2017. Journal of Psychopharmacology 2017: volume 31, issue 5, pages 519 to 552.

National Institute for Health and Care Excellence. Alcohol-use disorders: diagnosis, assessment and management of harmful drinking (high-risk drinking) and alcohol dependence (CG115). NICE, 2011.

National Institute for Health and Care Excellence. Pregnancy and complex social factors: a model for service provision for pregnant women with complex social factors (CG110). NICE, 2010.

Nunes E and Levin F. Treatment of depression in patients with alcohol or other drug dependence: a meta-analysis. JAMA 2004: volume 291, issue 15, pages 1,887 to 1,896.

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10. Pharmacological interventions

10.1 Main points

10.2 Context

10.2.1 General principles

10.2.2 Off-label or unlicensed use of medicines: prescribers’ responsibilities

10.2.3 The importance of setting and staff skills

10.2.4 Setting for medically assisted withdrawal based on severity of dependence and complexity of need

Planning the setting and regimens

Criteria for specialist inpatient medically assisted withdrawal

Lower threshold referrals

Support for community medically assisted withdrawal

10.2.5 Specific groups

10.3 Prescribing medication for management of withdrawal from alcohol

10.3.1 Main purpose of medication in medically assisted withdrawal

10.3.2 Planned and unplanned withdrawal

10.3.3 Benzodiazepine withdrawal regimens

10.3.4 Choice of regimen

10.3.5 Choice of medication

Chlordiazepoxide, diazepam and other benzodiazepines

Chlordiazepoxide and possible risk of genotoxicity (damage to genetic information)

10.3.6 Using carbamazepine as an alternative to a benzodiazepine for managing withdrawal

10.3.7 Using clomethiazole

10.4 Prescribing medication to prevent and to manage specific complications of withdrawal

10.4.1 Preventing and managing withdrawal seizures

Withdrawal seizures

Preventing withdrawal seizures

10.4.2 Preventing and managing delirium tremens

Identifying delirium tremens

Preventing delirium tremens in medically assisted withdrawal

Managing established delirium tremens

10.4.3 Preventing and managing Wernicke’s encephalopathy

Thiamine prophylaxis to prevent WE

Pharmacological regimen for thiamine prophylaxis

Treatment for incipient Wernicke’s encephalopathy

Preventing Wernicke’s encephalopathy in people who continue to drink alcohol

10.5 Pharmacological interventions for preventing relapse and promoting abstinence

10.5.1 Principles for prescribing for relapse prevention and promoting abstinence

Planning medication to support relapse prevention

Integrating pharmacological and psychosocial interventions in community alcohol treatment services or primary care

10.5.2 First-line pharmacological interventions

Acamprosate

Indications

Baseline investigations and monitoring

Dose schedule

Suggested dose schedule in renal impairment

Prescribing arrangements

Naltrexone

Indications

Specific considerations

Baseline investigations and monitoring

Dose schedule

Prescribing arrangements

Choosing between acamprosate or naltrexone as first-line treatment

10.5.3 Second-line pharmacological interventions

Disulfiram

Indications

Baseline investigations and monitoring

Dose schedules

Prescribing arrangements

Baclofen

Use of baclofen in the UK

Indications

Baseline investigations and monitoring

Dose schedules

Prescribing arrangements

10.5.4 Other drugs used for relapse prevention

10.5.5 Drugs that should not be used for relapse prevention

Antidepressant medication

Benzodiazepines and z-drugs

10.5.6 Pharmacological intervention to reduce alcohol use: nalmefene

Use of nalmefene in the UK

Indications

Specific considerations

Baseline investigations and monitoring

10.6 Pharmacological interventions for specific groups of people

10.6.1 Pharmacological treatments for people using alcohol and other drugs or medications

Co-occurring alcohol and opioid dependence

Management of withdrawal from alcohol for people with opioid dependence

Medication for relapse prevention