Management of Alcohol Dependence with Medications
Alcohol dependence is a condition that is characterised by a lack of control surrounding drinking – less than 5% of dependent drinkers are able to return to a state of controlled drinking.  As a result, those who are categorised as dependent drinkers are strongly advised to abstain from alcohol entirely.
This process usually requires a significant amount of support and treatment to prevent relapse. Full abstinence is not always possible (or acceptable to the drinker) to start with – treatment featuring a range of different steps at different intervals are usually required.
This treatment will need continued follow-up interactions, repeated advice, and motivational techniques in order to help achieve release from alcohol dependence.
What are the Main Steps in the Management of Alcohol Dependence?
Below, we outline the main steps in the management of alcohol dependence:
- Information and education
- Acceptance of the need to abstain from drinking alcohol and commitment to abstaining from drinking
- Management and treatment of alcohol withdrawal effects
- Pharmacotherapies in order to help suppress the ‘need’ to drink
- Psychological therapies to support both the side effects of abstinence and causes of dependence
- Management of complications or co-morbidity (whether these be medical, social, or psychiatric)
- Support from and for close family and friends
- Groups for mutual support
- Follow up care
- Personal change, lifestyle change, and environmental change
What are Pharmacotherapies and How Can They Help?
Pharmacotherapy is the use of prescribed medical drugs that help to reduce cravings or reduce the rewards of drinking alcohol. They are usually prescribed to those recovering from alcohol dependence to prevent relapse after the acute alcohol withdrawal period is over.
This separation from the alcohol withdrawal period and the start of pharmacotherapy is important as it helps to determine whether side effects such as nausea are due to withdrawal, or medication. To ensure patients are well supported and comply with medication guidance, regular follow-up sessions are required.
What are the Different Pharmacotherapies Available?
We list each type of pharmacotherapies available for the management of alcohol dependency:
1. Opioid Antagonists: Naltrexone and Nalmefene
In the short-term, alcohol is believed to produce feelings of well being through the release of endorphins. This contributes overall to the ‘reward’ factor of drinking alcohol – a factor which is likely to encourage relapse or reinforce the behaviour of drinking. Naltrexone and Nalmefene are examples of Opioid Antagonists.
These are medications that help to block the pleasurable effects of alcohol, removing the ‘reward’ factor that can lead to relapse, and it is through that they can also reduce cravings for alcohol.
Studies have demonstrated these effects, with double-blind placebo-controlled research showing that with the use of Naltrexone at a 50mg/day dose over a 3-month period significantly cut relapse rates. To have this effect, however, the pharmacotherapy should be used with the support of psychotherapy.
Naltrexone usually lasts for a 24-hour period and is absorbed through the gastrointestinal tract. Nalmefene is a longer-acting substance which is usually administered through injection. It can last over a period of weeks to months, therefore improving compliance with treatment.
Those starting to take naltrexone may be initially given a 25mg half-dose for the first few days. This is to reduce any side effects such as diarrhoea or nausea – after a short period, this can be increased to the full dose of 50mg.
It is important to note that opioid antagonists are only intended to be a means to assist recovery from alcohol dependence – they should be prescribed alongside other treatments in order to provide a comprehensive program of recovery.
It is also important to recognise that although it is possible to prescribe opioid antagonists to an individual who is still drinking alcohol, the effectiveness of the medication is likely to be inhibited. Studies have only demonstrated effectiveness for those who have already abstained from alcohol for five days or more.
There are a number of cautions to the use of opioid antagonists. If an individual on opioid antagonists needs elective surgery, they should discontinue taking the medication for a minimum period of 72 hours prior to the surgery taking place.
Antagonists block the effects of opioid analgesia – in case emergency analgesia is required, those on naltrexone should carry a card warning that they are on that particular medication. This means that emergency medical professionals can adjust their treatment in order to accommodate the presence of this medication and closely monitor for potential side effects.
2. Acamprosate (Calcium Acetylhomotaurinate)
Acamprosate is thought to help reduce cravings for alcohol through antagonising excitatory glutamate (at the NMDA receptor) and potentially also stimulating inhibitory GABA-ergic transmissions. It is absorbed slowly over a period of 4 hours in the gastrointestinal tract, with peak concentrations being reached after approximately 5 to 7 hours. Levels of the acamprosate are stabilised after around 1 week.
In a meta-analysis of trials, acamprosate has been shown to have effects significantly superior to those of a placebo in helping to increase periods of abstinence of alcohol, and in preventing relapses.
Disulfiram acts as a psychological deterrent to drinking alcohol. It works to inhibit aldehyde dehydrogenase, which leads to acetaldehyde (a noxious compound) accumulating after drinking even small qualities of alcohol. the unpleasant reaction of this noxious compound acts as the deterrent. The effects of disulfiram take action within 12 hours, and they will last for approximately 5 to 6 days. 
The reaction that is triggered by disulfiram is highly unpleasant, potentially to the point of the individual taking the medication becoming bed-bound while the effects last. The side effects usually occur within the first 10 minutes after consuming the alcohol and will peak at approximately 20 to 30 minutes. They can include flushing, headaches, heart palpitations, dyspnoea, feelings of nausea, hypotension, and prostration. 
This reaction can be caused inadvertently due to the sensitivity of the disulfiram – alcohol-containing cough mixtures or food dressings or sauces can be enough to trigger the side effects. It is important for those on this medication to be extremely aware of any substance that they put into their body.
Aversive therapy of this kind has been found to be incredibly effective in reliable and motivated patients who have been well supported and are immersed in a comprehensive program of treatment.
Doses should be given under close supervision from professionals, and the patient taking the medication needs to be able to comprehend and consent to the use of the disulfiram. It is recommended that the daily doses are supervised by either a clinic, pharmacy, or a responsible family member.
It is important for patients taking disulfiram to abstain from drinking alcohol for at least 24 hours prior to taking the first dose, and for at least 1-week post cessation of the treatment.
It is also vital for patients looking to start treatment to understand the potential contraindications, which include psychosis, hypersensitivity to thiuram derivatives (such as pesticides or rubber), cognitive impairment (which can impede on the understanding of or the recall of the medication’s side-effects), ischaemic heart disease, or severe renal or hepatic disease.
Disulfiram is currently available in doses of 200mg (in tablet form), which is usually started at a half dose of 100mg per day for the first 1 to 2 weeks to allow for adjustment. Treatment can last anywhere from 6 weeks to 6 months depending on the degree of treatment success, and the preferences of the patient. For some patients, lifelong treatment is preferred. 
What Other Medications are Under Study?
Below, we list these medications under study:
This medication is currently prescribed for the treatment of involuntary muscle spasms. However, it has shown considerable promise in the treatment of alcohol withdrawal and the craving of alcohol.
Currently licensed as an anti-emic medication, ondansetron has been shown in a study to reduce the alcohol consumption of participants in examples of early-onset alcohol dependence in men.
This medication is relatively new. Its main purpose is to act as an anticonvulsant, but it has been involved in a number of controlled trials in alcohol dependence with indications of success. It requires more study, as the adverse effects of sedation and unsteadiness have proved to be problematic.
Topiramate also leads to weight loss, which can be either a positive or negative impact depending on the pretreatment conditions of the individual in question.
The Choosing and Combining of Medications
There is no current advice available on the choice or combining of medications. Which medication will be most effective depends on each individual and their journey to alcohol dependency recovery.
Naltrexone is a drug that offers the benefits of once-daily dosing and may be particularly beneficial for those you drink in binges as it reduces the ‘reward’ factors of drinking. However, it does have some gastrointestinal side effects.
Acamprosate tends not to have these side effects and unlike naltrexone, can be used in those who require doses of opioid analgesia. However, dosing is required three times a day. For recovering individuals, this can provide issues in compliance with treatment.
Naltrexone and Acamprosate can be combined – especially for those you have a more severe dependence on alcohol, and those where monotherapy treatment has failed.
Either or both Naltrexone and Acamprosate can be combined with Disulfiram.
Pharmacotherapy should always be undertaken as part of a comprehensive program of recovery that includes efforts to ensure patient compliance. The amount of time that pharmacotherapy is required is highly dependent on each individual and their needs, but the greatest risk of relapse is generally within the first 3 months.
Most clinicians would generally advise that pharmacotherapy is continued for up to one year. Further research is required into the taking of these medications for longer periods of time.
 Law FD, Nutt DJ. Drugs used in the treatment of the addictions. New Oxford Textbook of Psychiatry,
2nd edn [in press, 2008].