Alcohol use disorder

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

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Alcoholmisbruik bij jongerenPublished by: Federaal Wetenschapsbeleid (Belspo)Last published: 2015Alcoholmisbruik bij jongerenPublished by: Federaal Wetenschapsbeleid (Belspo)Last published: 2015

Treatment usually consists of the following components:

Brief intervention, particularly in unhealthy alcohol use and mild alcohol use disorder
Individual therapy
Psychosocial support
Drug treatment to support reduced alcohol intake and abstinence
Ongoing support to help the patient maintain their goals regarding alcohol intake

Patients may benefit from a combination of interventions, and the use of one should not preclude the use of another.[77][78]

Goals of treatment may include abstinence, reduction or moderation of alcohol use, or other elements of harm reduction, and should be agreed between patient and clinician. The patient’s legal obligations, and risk of harm to self or others from alcohol use, should also be discussed.[51]

The appropriate level of care for a patient is determined via six dimensions:

Withdrawal risk
Biomedical conditions or complications
Stability of co-occurring mood disorders and cognitive status
Readiness to change
Likelihood of return to use
Living environment and psychosocial support.

Patients who are medically unstable or do not meet their goals with outpatient management can be stepped up to a higher level of care.[3] Lack of access to a higher level of care, however, should not prevent clinicians from offering drug treatment, support services, and harm reduction strategies.

Engagement and retention in any substance use treatment can be a major clinical challenge; it is recommended that healthcare providers proactively engage people who would benefit from treatment at all stages of readiness for change, including those who are uninterested or ambivalent about receiving treatment.[3]

The following strategies are amongst those recommended by the American Society of Addiction Medicine to improve treatment engagement and retention:[3]

Cultivate patient trust by creating a welcoming, non-judgemental and trauma-sensitive environment
Do not require abstinence as a condition of treatment initiation or retention
Build connections to people with a substance use disorder who are not currently seeking treatment
Seek to re-engage individuals who disengage from care
Develop treatment plans that are responsive to the individual’s needs and priorities
Address the physical, psychological, social, and cultural factors that contribute to substance use and recovery

Alcohol use treatment programmes should provide integrated care and address co-occurring mental and physical health conditions, as required, which may influence effective participation in treatment.[3]

[Figure caption and citation for the preceding image starts]: Treatment overviewCreated by BMJ Knowledge Centre [Citation ends]. com.bmj.content.model.Caption@33f101ac

Management of withdrawal

One of the most life-threatening complications of alcohol use disorder is alcohol withdrawal. As a result, telling patients who use alcohol daily to stop drinking abruptly could be dangerous. At the time of assessment, patients should be assessed with a structured instrument, such as the revised Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar), to determine the severity of the alcohol withdrawal syndrome (AWS).[79] Clinical Institute Withdrawal Assessment of Alcohol Scale, revised (CIWA- Ar) Opens in new window

Severity guides the management of alcohol withdrawal, which centres on benzodiazepines as first-line drug treatment, close monitoring, correction of fluid and electrolyte imbalance, and consideration of thiamine (vitamin B1) to prevent Wernicke's encephalopathy and Korsakoff syndrome. See Alcohol withdrawal.

Brief interventions

People with unhealthy alcohol use that do not meet alcohol use disorder criteria can often be treated with a brief intervention. These interventions are typically 5-15 minutes long, follow a structured outline, provide education, and may or may not include follow-up treatment. In patients with at-risk drinking, these interventions reduce total alcohol consumed.[42][80][81] Most studies excluded patients with moderate to severe alcohol use disorder, and evidence for the effectiveness of brief intervention without referral to treatment in this population, as well as in those with multiple substance use disorders, is lacking.

Brief interventions can consist of one or more sessions in the clinic or hospital setting (e.g., emergency department or inpatient unit), during which education and feedback about the patient's alcohol use and its consequences are provided in a supportive and empathic fashion. [ ] Brief interventions may be improved by follow-up; for instance, one multi-site randomised controlled trial (RCT) in the trauma setting showed improvement in several drinking measures at up to 12 months for patients who received an individualised follow-up phone call in addition to brief motivational interviewing, compared with those who just received the interview.[82] A formal means of assessing the effectiveness of the plan and follow-up visits with the clinician should be part of the plan.[83] Though brief interventions are easy to administer, they go beyond simply telling patients to reduce their alcohol use: in studies of their effectiveness, clinicians were trained to provide structured feedback based on an individual’s risk and desire to change their behaviour. One commonly used structure is the FRAMES method: Feedback, Responsibility, Advice, Menu of options, Empathic style, Self-efficacy.

[Figure caption and citation for the preceding image starts]: FRAMES method for brief interventionAdapted by Best Practice topic authors from: Bien TH et al. Addiction. 1993 Mar;88(3):315-35 [Citation ends]. com.bmj.content.model.Caption@4b80bd8f

Motivational interviewing

Motivational interviewing (MI, a technique that assists the patient in identifying their own goals) can be an effective, patient-centred way of engaging patients in treatment and reducing substance use.[3][42][84] MI requires clinicians to avoid confronting, labelling, or directing the patient, but rather to elicit the patient’s ambivalence and support his/her motivation to change through open-ended questions, affirmations, reflective statements, and summarising. It can be implemented effectively in community settings if clinicians are trained in this approach.[3][42]

There are quality limitations, however, to the evidence on MI. One Cochrane systematic review found that MI may be effective in reducing substance use in the immediate- to short-term (compared with no treatment), but had no effect on readiness to change behaviour.[85] Studies were heterogeneous, with no evidence specific to alcohol use.

Psychosocial interventions

Non-pharmacological approaches can be useful for many patients with alcohol use disorder, as they provide strategies to help patients avoid returning to alcohol use, enhance self-efficacy, and reduce the impact of stressors that can precipitate return to use. Interventions may be individual or group-based. There is no strong evidence for any one approach, and therefore patient preference and local availability should guide treatment choice.[42][86][87]

US guidelines from the Department of Veterans Affairs/Department of Defense (VA/DoD) suggest the following as first-line options that have demonstrated modest effect on alcohol consumption and recovery:[42]

Cognitive behavioural therapy (CBT, assists patients in coping with thoughts of return to alcohol use and negative cognitions)
Behavioural couples therapy (BCT, aims to improve relationship functioning with goals to reduce alcohol use with partner support)
Community reinforcement approach (CRA, comprehensive cognitive behavioural approach that addresses environmental contingencies that influence drinking behaviour)
Motivational enhancement therapy (MET, based on the principles of motivational interviewing but using a structured, individualised plan incorporating assessment and feedback to enhance self-efficacy)
12-step facilitation (TSF, systematised approach that aims to enhance engagement in Alcoholics Anonymous [AA] or other 12-step based self-help groups)

Outpatient and intensive outpatient treatment programmes typically include treatment sessions scheduled from once- or twice-weekly to several times a week, with treatment extending over several weeks to months (or longer).

AA, founded in 1939, is the most common programme. Its primary goal is to help individuals maintain total abstinence from alcohol and other addictive substances. Alcoholics Anonymous Opens in new window [ ] [Evidence A] Self-help programmes such as AA can provide valuable additional support for many patients and their families. Patients indicating benefit from support group attendance should be encouraged to attend the group meetings over an extended timeframe; some patients may benefit from attending indefinitely. In one large RCT, AA improved drinking outcomes, largely through improvements in adaptive social network changes and social self-efficacy.[88] Each AA group is independent, so patients should be encouraged to try several if one is not a good fit. For those who have negative experiences or views of AA, it is important that clinicians are aware of alternatives, such as Smart Recovery groups.

When provided alongside pharmacological treatment or other first-line psychosocial interventions, the VA/DoD reports evidence to support options of CBT, MET or TSF.[42] MET strategies, in particular, have been recognised to encourage engagement and retention in care.[3] One Cochrane systematic review found moderate-certainty evidence that, compared with psychosocial therapy alone, adding pharmacological treatment was safe and reduced the number of ‘heavy drinkers’, though an effect on other outcomes (such as volume and frequency of consumption or treatment retention) was unclear.[89] It was also uncertain whether adjunctive psychosocial therapy gave benefit compared with pharmacological treatment alone. Most studies have evaluated CBT adjunctive to naltrexone, in people without comorbid mental health or substance use disorder.[89] An earlier meta-analysis of six studies had found the addition of manualised CBT did not improve return-to-use rates when added to naltrexone therapy.[90]

The following table summarises psychological interventions in the outpatient setting.

[Figure caption and citation for the preceding image starts]: Non-pharmacological approaches can be useful for many patients with alcohol use disorder, as they provide strategies to help patients avoid returning to alcohol use, enhance self-efficacy, and reduce the impact of stressors that can precipitate return to useTable created by authors of the Best Practice topic [Citation ends]. com.bmj.content.model.Caption@1e8ef5e2

Pharmacological treatment

Pharmacological treatment can help support abstinence, reduce alcohol consumed, and reduce the number of heavy drinking days, all of which are likely to reduce harm from alcohol use.[77] Nonetheless, drug therapy for alcohol use disorder remains underutilised because of lack of clinician and patient familiarity, and perhaps a tendency to discount outcomes other than abstinence as worthwhile clinical goals. Three drugs - naltrexone, acamprosate, and disulfiram - are approved by the US Food and Drug Administration (FDA) for the treatment of alcohol use disorder. Naltrexone, acamprosate, and disulfiram have been studied in patients with moderate to severe alcohol use disorder, but may be offered to patients with mild alcohol use disorder on a case-by-case basis.[42][51] The use of pharmacological treatment does not preclude other psychosocial support; and psychosocial support does not preclude the use of pharmacological treatment. Indeed, the greatest efficacy may be seen in patients using a combination of drug therapy and psychosocial treatment.[77] However, patient choice to decline psychosocial treatment should not preclude or delay pharmacotherapy.[3]

Guideline recommendations on first-choice pharmacotherapy differ slightly. For patients with moderate-severe alcohol use disorder who desire abstinence, the American Psychiatric Association (APA) recommends offering naltrexone or acamprosate unless contraindicated, with choice guided by patient characteristics, mode of administration and potential adverse effects.[51] Disulfiram is suggested as a second-choice option (for reasons of preference, intolerance or non-response) provided that the patient is aware of the risks from continued alcohol consumption. Topiramate or gabapentin (both off-label for this indication) are also suggested as second-line alternatives if indicated by ease of administration, preferred adverse effects profile or contraindications to other drugs.[51]

The VA/DoD recommends naltrexone or topiramate as first-choice options, with a weaker suggestion to offer acamprosate or disulfiram. Selection of topiramate is guided by demonstrated efficacy, including among veterans, specifically. Gabapentin is suggested if first-line drug therapy is contraindicated or ineffective.[42]

Nonetheless, guideline groups are unanimous in emphasising the importance of informed patient choice, with patient preferences and care needs central to treatment planning.[3][51][42]

It is suggested that drugs are continued for at least 6 months due to the chronic, relapsing nature of the condition.[77] Further treatment is determined through shared decision-making.

Naltrexone is an opioid receptor antagonist that decreases alcohol use by attenuating the rewarding and reinforcing effects of alcohol. Specifically, naltrexone blocks stimulation of the opioid receptor by endogenous opioids and decreases dopamine release in the ventral tegmental area.[91] It is particularly useful in patients with a family history of alcohol use disorder and in those with significant alcohol cravings.[16][51][92] Oral naltrexone can be started in patients who are still drinking, and it is usually well-tolerated. Naltrexone can precipitate opioid withdrawal in those with opioids in their system. It is not started until patients have been opioid-free for several days (7-10 days) and is contraindicated in those who require opioid agonists for pain or opioid use disorder. Naltrexone can cause stomach discomfort and a mild increase in liver function tests, especially in the oral formulation. As such, the oral formulation is not recommended in patients with alanine aminotransferase (ALT) measurements greater than 5 times the normal limit. Intramuscular naltrexone appears to be safe except in acute liver failure or decompensated cirrhosis. As it does not undergo first pass metabolism in the liver, serum concentration is more predictable and it is considered safer.[93][94][95] Treatment with naltrexone reduces heavy drinking days, improves abstinence, and reduces the risk of returning to any or heavy drinking at 3 and 12 months post-treatment, compared with placebo.[96] [ ] In one meta-analysis of 118 RCTs, the number needed to treat (NNT) to prevent return to drinking for oral naltrexone was 18, and the NNT to reduce heavy drinking was 11.[97] The intramuscular formulation of naltrexone may be more effective in patients with difficulty taking daily drug treatments, with some evidence that it can reduce percentage drinking days (5% reduction vs. placebo).[97][98] Naltrexone is supported as a first-line drug option for alcohol use disorder, in conjunction with psychosocial therapy.[51][97][99] It can be used as a monotherapy or in combination with gabapentin, topiramate, acamprosate, or disulfiram (unless specific drugs are contraindicated).
Acamprosate normalises glutamate and gamma-aminobutyric acid neurotransmitter systems in the central nervous system. It is thought that these actions reduce ongoing symptoms associated with alcohol abstinence (e.g., anxiety, insomnia) and cravings. It is primarily metabolised by the kidneys, and a dose reduction may be required in patients with renal impairment (its use is contraindicated if creatinine clearance is <30 mL/minute).[51] Acamprosate increases the rate and duration of abstinence, compared with placebo.[100][101] Acamprosate is safe to use in patients who are actively drinking, but evidence for its use is from trials in people who have already stopped drinking. In meta-analysis, the NNT is 11 to prevent return to any drinking.[97] Diarrhoea is a common adverse effect.[97] Naltrexone and acamprosate are considered to be equally efficacious, with both supported as first-choice pharmacotherapy options.[51][97][99] [ ] However, pill burden may reduce its effectiveness, and can limit use of acamprosate in clinical practice.
Gabapentin is approved for the treatment of partial seizures and neuropathic pain. The exact mechanism of gabapentin in alcohol use disorder is not known, but it appears to inhibit the release of excitatory neurotransmitters. In an RCT of 96 individuals with alcohol use disorder, gabapentin resulted in a statistically significant decrease in heavy drinking days (NNT 5) and prevented return to use (NNT 6) for patients with high baseline alcohol withdrawal symptoms.[102] However, the largest RCT to date (346 patients), which used the extended-release formulation, found no benefit compared with placebo.[103] Meta-analyses have concluded a low strength of evidence for gabapentin overall, with any effects on drinking outcomes being of only borderline statistical significance.[97][99] Nevertheless, gabapentin may be an effective option in patients with symptoms of alcohol withdrawal, or when other drugs are contraindicated or poorly tolerated.[42][51] It can be used as monotherapy or in conjunction with naltrexone.[104] The main side effects of gabapentin are dizziness, drowsiness, and nausea. Patients should be counselled that abrupt cessation of gabapentin can lower the seizure threshold.
Topiramate is an anticonvulsant that has been shown in RCTs to decrease craving and withdrawal symptoms and significantly improve physical and psychosocial well-being of patients with alcohol use disorder, compared with placebo.[105][106][107][108][109] In meta-analysis, compared with placebo, topiramate reduced percentage drinking days by 7%, heavy drinking days by 6%, and the number of drinks per drinking day by 2.[97] Importantly, efficacy has been established in subjects who were drinking at the time of starting the drug.[110] One study has shown that only individuals who are homozygous for the gene that codes for the kainate receptor protein had a reduction in heavy drinking days with topiramate treatment.[111] The benefits of topiramate should be weighed against the number needed to harm given its high side effect profile, including blurred vision, paraesthesias, poor memory, and loss of coordination.[97] Topiramate has been poorly tolerated in clinical trials, causing twice as many dropouts due to adverse effects as placebo.[99]
Disulfiram blocks the catabolic pathway of alcohol by inhibiting aldehyde dehydrogenase, thereby increasing acetaldehyde levels following alcohol ingestion. The disulfiram-alcohol reaction can produce a number of somatic effects: vasomotor symptoms (flushing), cardiovascular symptoms (tachycardia, hypotension), digestive symptoms (nausea, vomiting, diarrhoea), headache, respiratory depression, and malaise. These symptoms are generally transient, but serious reactions may occur that require urgent medical treatment. Due to hepatotoxicity, disulfiram is also contraindicated in patients with comorbid alcohol-related liver disease.[43] Disulfiram is prescribed for those intending to abstain from alcohol use, acting through negative reinforcement to promote abstinence. Trials to support disulfiram use are limited. One meta-analysis showed that disulfiram was more effective than placebo, acamprosate or naltrexone in open-label RCTs; a finding supported by subsequent network meta-analysis.[99][112] However, meta-analyses limited to blinded RCTs have not demonstrated a benefit of disulfiram.[97][112] Blinded studies are difficult to conduct, because the effectiveness of disulfiram depends on the patient's anticipation of somatic effects. Disulfiram therapy is more effective when supervised.[112]

The following table summarises the drugs, their mechanism of action, and effectiveness for reducing drinking behaviour or to achieve abstinence.

[Figure caption and citation for the preceding image starts]: Summary of the drugs, their mechanism of action, and effectiveness for reducing drinking behaviour or to achieve abstinenceCreated by BMJ Knowledge Centre with information from: Anton RF et al. JAMA Intern Med 2020;180(5):728-36; McPheeters M et al. JAMA 2023;330(17):1653–1665; Falk DE et al. Alcohol Clin Exp Res 2019;43(1):158-169 [Citation ends]. com.bmj.content.model.Caption@6e34d830

Evidence for the effectiveness of both psychosocial and pharmacological interventions for harmful alcohol use is from high-income countries, with no evidence available from low- and middle-income countries.[113]

Management of medical comorbidities

Patients with unhealthy alcohol use often have co-existing high blood pressure, insomnia, weight gain, cognitive disturbances, gastrointestinal distress, and cardiac arrhythmias. It is important to emphasise that many of these conditions may worsen with alcohol use, even at low levels. Management of physical comorbidities and timely integrated care is important to improve the well-being of the patient, and supports engagement in care.[3][114] Chronic care management reduces harms of alcohol use disorder in patients with medical comorbidities.[115] Treatment programmes should have provision for external referral to medical services when indicated.[3]

Pregnant women

Psychosocial interventions may increase abstinence rates, compared with usual care or no intervention, in pregnant women who consume alcohol.[116][117] It is unclear whether psychosocial therapies affect the number of drinks per day, though the evidence is overall of low quality, and predominantly relates to brief interventions.[117]

There are no RCTs evaluating the effectiveness of pharmacological interventions to reduce alcohol use or improve maternal, birth, and infant outcomes in pregnant women who consume alcohol or with alcohol use disorder.[117][118] Due to the lack of evidence and increased risk of harm, the use of drug therapy during pregnancy is usually limited in clinical practice, where possible. However, given the impact of alcohol on pregnancy, pharmacotherapy may still be considered for women who are unable to stop drinking without pharmacological support.

Naltrexone is the best-studied in pregnant patients, although primarily in opioid use disorder, and is not associated with birth defects.[119] It is generally recommended to switch to the oral formulation at 36 weeks’ gestation to allow for effective pain management at birth.

Acamprosate is also an option if the benefits outweigh the risks, but its efficacy in this population is unclear.[120]

Gabapentin may lead to withdrawal in neonates, especially in pregnant women with co-occurring alcohol use disorder.

Topiramate is contraindicated in pregnancy. Topiramate is associated with a higher risk of congenital malformations and a high prevalence of babies being born small for gestational age.[121] It may also be associated with an approximately 2 to 3 times increased risk of intellectual disability, autistic spectrum disorders and attention deficit hyperactivity disorder.[122]

In some countries, topiramate is contraindicated in pregnancy and in women of child-bearing age unless the conditions of a pregnancy prevention programme are fulfilled to ensure that women of child-bearing potential: are using highly effective contraception; have a pregnancy test to exclude pregnancy before starting topiramate; and are aware of the risks associated with use of the drug.[121][123]

Disulfiram is not recommended in pregnant patients due to its gastrointestinal side effects and lack of safety data.

Adolescents

One meta-analysis of 16 studies demonstrated that psychosocial interventions are effective in reducing adolescent alcohol use, with individual-directed treatments possibly having a greater effect than family-based ones. Interventions with large effect sizes included brief motivational interviewing, cognitive behavioural therapy with 12 steps, cognitive behavioural therapy with aftercare, multidimensional family therapy, brief interventions with the adolescent, and brief interventions with the adolescent and a parent.[124] Group therapy-based treatments may be effective for adolescents, but safety should be considered and these modalities require further investigation.[125]

Naltrexone has been found to reduce cravings in adolescents in a few small trials. Acamprosate has likewise shown promise. Disulfiram can be useful for adolescents motivated to stop drinking, but has poor efficacy in those who do not desire abstinence and are not receiving it in directly observed therapy.[126] However, given the overall lack of evidence and increased risk of harm, the use of drug therapy in adolescents is usually limited in clinical practice, where possible.

Concurrent opioid use

It is recommended that patients have access to evidence-based treatment for all substance use concerns, and that secondary substance use is not considered a barrier to care.[3] Several step-by-step treatment recommendations have been developed to integrate psychosocial therapies with pharmacological therapies for alcohol and drug use disorders.[127][128] These procedures include patient education, personalised feedback, emotional support, drug monitoring, and motivational enhancement. National Institute on Alcohol Abuse and Alcoholism (NIAAA) Opens in new window

Choice of first-line pharmacological treatment options vary in people with concurrent opioid use. Naltrexone can precipitate opioid withdrawal in those with opioids in their system, so should be avoided. It is not started in patients until they have been opioid-free for several days (7-10 days) and is contraindicated in patients who require opioid agonists for pain or opioid use disorder.

Acamprosate and gabapentin may be used in patients with concurrent opioid use and alcohol use disorder. Evidence indicates that patients with opioid use disorder and polydrug users are at risk for gabapentin misuse and clinicians should monitor usage closely.[129] Patients should also be counselled that abrupt cessation can lower seizure threshold.

Topiramate and disulfiram are second-line options.

Sedating substances or drug (e.g., benzodiazepines, barbiturates, opioids, muscle relaxants) may have similar signs and symptoms as alcohol use disorder, or may be used together with alcohol. Use of these substances with alcohol may pose risk for overdose complications (e.g., respiratory depression).

Concurrent mental health diagnosis

Symptoms of alcohol use disorder (including those of intoxication/withdrawal) may be confused with symptoms of other psychiatric disorders. Furthermore, other psychiatric disorders can co-occur with alcohol use disorder. Observation over days to weeks to months may be necessary to clarify underlying psychiatric diagnoses. However, co-treatment generally has better outcomes than waiting for patients to stop drinking before making a diagnosis or starting psychiatric treatment; therefore, treatment should not be withheld until patients stop drinking.

Psychosocial treatments for alcohol use disorder, and naltrexone, can be used first-line. However, note that evidence (from high-income countries) on the effectiveness of psychosocial interventions in alcohol use disorder primarily relates to patient populations without comorbid mental health illness, with no studies including people with severe mental health illness.[87] Acamprosate, gabapentin, topiramate, or disulfiram may be considered as alternative drug options to naltrexone, with selection guided by contraindications, tolerance, and patient preference.

One meta-analysis of 15 RCTs demonstrated reduced alcohol use and improved psychiatric outcomes when co-occurring depressive and anxiety disorders were treated concurrently with alcohol use disorder.[130] Treatment options depend on diagnosis and may include antidepressants. Selective serotonin-reuptake inhibitors (SSRIs) have demonstrated efficacy in alcohol use disorder for patients with comorbid depression. Sertraline, when compared with placebo, decreases the proportion of days drinking during treatment and increases the number of patients who had continuous abstinence. Its efficacy was higher in those with more mild alcohol use disorder.[131] Trials of fluoxetine for alcohol use disorder achieved similar results, suggesting that fluoxetine may also be effective in mild alcohol use disorder.[132] However, not all studies have supported the utility of SSRIs for treating alcohol use disorder. One study of fluoxetine for people with alcohol use disorder and co-occurring depression demonstrated no benefit of fluoxetine versus placebo on either depression or drinking.[133]

For more details on management of depression see Depression in adults.

Treatment programmes should have provision for external referral to psychiatric services, or to a more intensive level of care, when indicated.[3] In patients with suspected or diagnosed bipolar disorder, psychiatric consultation is strongly recommended.

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