Treatment algorithm

Your Organizational Guidance

ebpracticenet urges you to prioritize the following organizational guidance:

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

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

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at-risk drinking

1st line – brief interventions

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at-risk drinking
1st line – 

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][77][78]​​​ 

Brief interventions can consist of one or more sessions in the physician's office or in a 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. [ Cochrane Clinical Answers logo ] ​​​ Brief interventions may be improved by follow-up; for instance, one multisite randomized controlled trial in the trauma setting showed improvement in several drinking measures at up to 12 months for patients who received an individualized follow-up phone call in addition to brief motivational interviewing, compared with those who just received the interview.[79]​ A formal means of assessing the effectiveness of the plan and follow-up visits with the physician should be part of the plan.[80]​ 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 behavior. 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@348e3923

Plus – management of medical comorbidities

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at-risk drinking
Plus – 

management of medical comorbidities

Treatment recommended for ALL patients in selected patient group

Patients with unhealthy alcohol use often have coexisting high blood pressure, insomnia, weight gain, cognitive disturbances, gastrointestinal distress, and cardiac arrhythmias. It is important to emphasize 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][111]​ Chronic care management reduces harms of alcohol use disorder in patients with medical comorbidities.​[112]​  Treatment programs should have provision for external referral to medical services when indicated.[3]

1st line – motivational interviewing

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at-risk drinking
1st line – 

motivational interviewing

Motivational interviewing (MI, a technique that assists the patient in identifying their own goals) can be an effective, patient-centered way of engaging patients in treatment and reducing substance use.[3][42][81] MI requires clinicians to avoid confronting, labeling, 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 summarizing. 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 behavior.[82]​ Studies were heterogeneous, with no evidence specific to alcohol use.

Plus – management of medical comorbidities

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ONGOING
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at-risk drinking
Plus – 

management of medical comorbidities

Treatment recommended for ALL patients in selected patient group

Patients with unhealthy alcohol use often have coexisting high blood pressure, insomnia, weight gain, cognitive disturbances, gastrointestinal distress, and cardiac arrhythmias. It is important to emphasize 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][111]​ Chronic care management reduces harms of alcohol use disorder in patients with medical comorbidities.​[112]​ Treatment programs should have provision for external referral to medical services when indicated.[3]

alcohol use disorder: nonpregnant adult with no concurrent opioid use or mental health diagnosis

1st line – psychosocial treatment

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alcohol use disorder: nonpregnant adult with no concurrent opioid use or mental health diagnosis
1st line – 

psychosocial treatment

​Nonpharmacologic 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][83][84]​​

The Department of Veterans Affairs /Department of Defense suggests the following as first-line options that have demonstrated modest effect on alcohol consumption and recovery: cognitive behavioral therapy (CBT, assists patients in coping with thoughts of return to alcohol use and negative cognitions); behavioral couples therapy (BCT, aims to improve relationship functioning with goals to reduce alcohol use with partner support); community reinforcement approach (CRA, comprehensive cognitive behavioral approach that addresses environmental contingencies that influence drinking behavior); motivational enhancement therapy (MET, based on the principles of motivational interviewing but using a structured, individualized plan incorporating assessment and feedback to enhance self-efficacy); and 12-step facilitation (TSF, systematized approach that aims to enhance engagement in Alcoholics Anonymous [AA] or other 12-step based self-help groups).[42]

Outpatient and intensive outpatient treatment programs 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 program. Its primary goal is to help individuals maintain total abstinence from alcohol and other addictive substances. Alcoholics Anonymous Opens in new window [ Cochrane Clinical Answers logo ] [Evidence A]​​​​​​ Self-help programs 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 randomized controlled trial, AA improved drinking outcomes, largely through improvements in adaptive social network changes and social self-efficacy.[85]​ 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.

Reassess every 3 months for worsening use or harms of alcohol.

Plus – management of medical comorbidities

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ONGOING
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alcohol use disorder: nonpregnant adult with no concurrent opioid use or mental health diagnosis
Plus – 

management of medical comorbidities

Treatment recommended for ALL patients in selected patient group

Patients with unhealthy alcohol use often have coexisting high blood pressure, insomnia, weight gain, cognitive disturbances, gastrointestinal distress, and cardiac arrhythmias. It is important to emphasize 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][111]​ Chronic care management reduces harms of alcohol use disorder in patients with medical comorbidities.​[112] Treatment programs should have provision for external referral to medical services when indicated.[3]

1st line – naltrexone

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alcohol use disorder: nonpregnant adult with no concurrent opioid use or mental health diagnosis
1st line – 

naltrexone

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.[88] It is available in oral and intramuscular formulations. It is particularly useful in patients with a family history of alcohol use disorder and in those with significant alcohol cravings.[16][51][89]​​

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.[90][91][92]​​​​​

Treatment with naltrexone reduces heavy drinking days, increases abstinence, and reduces the risk of returning to any or heavy drinking at 3 and 12 months post-treatment, compared with placebo.[93] [ Cochrane Clinical Answers logo ] ​​​​​​​​ In one meta-analysis of 118 randomized controlled trials, 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.[94]​​ The intramuscular formulation of naltrexone may be more effective in patients with difficulty taking daily drug treatment, with some evidence that it can reduce percentage drinking days (5% reduction vs. placebo).[94][95]​​

Naltrexone is supported as a first-line drug option for alcohol use disorder, in conjunction with psychosocial therapy.[51][94][96]​ However, use in clinical practice may not always reflect this suggested position in care; guideline groups are unanimous in emphasizing the importance of informed patient choice, with patient preferences and care needs central to treatment planning.[3][42]​​[51]

Naltrexone can be used as a monotherapy or in combination with gabapentin, topiramate, acamprosate, or disulfiram (unless specific drugs are contraindicated).

It is suggested that drugs are continued for at least 6 months due to the chronic, relapsing nature of the condition.[75]​ Further treatment is determined through shared decision-making.​

Primary options

naltrexone: 50 mg orally once daily; 380 mg intramuscularly every 4 weeks

Plus – management of medical comorbidities

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ONGOING
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alcohol use disorder: nonpregnant adult with no concurrent opioid use or mental health diagnosis
Plus – 

management of medical comorbidities

Treatment recommended for ALL patients in selected patient group

Patients with unhealthy alcohol use often have coexisting high blood pressure, insomnia, weight gain, cognitive disturbances, gastrointestinal distress, and cardiac arrhythmias. It is important to emphasize 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][111]​ Chronic care management reduces harms of alcohol use disorder in patients with medical comorbidities.​[112] Treatment programs should have provision for external referral to medical services when indicated.[3]​​ ​​

Consider – psychosocial treatment

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ONGOING
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alcohol use disorder: nonpregnant adult with no concurrent opioid use or mental health diagnosis
Consider – 

psychosocial treatment

Treatment recommended for SOME patients in selected patient group

The use of pharmacologic treatment does not preclude other psychosocial support; and psychosocial support does not preclude the use of pharmacologic treatment. Indeed, the greatest efficacy may be seen in patients using a combination of pharmacotherapy and psychosocial treatment.[75]​ However, the patient’s decision to decline psychosocial treatment should not preclude or delay pharmacotherapy.[3]

When provided alongside pharmacologic treatment or other first-line psychosocial interventions, the Department of Veterans Affairs /Department of Defense report evidence to support options of cognitive behavioral therapy (CBT), Motivational Enhancement Therapy (MET) or 12-Step Facilitation of programs such as Alcoholics Anonymous.[42]​ MET strategies, in particular, have been recognized to encourage engagement and retention in care.[3]

One Cochrane systematic review found moderate-certainty evidence that, compared with psychosocial therapy alone, adding pharmacologic treatment was safe and reduced the number of "heavy drinkers", but an effect on other outcomes (such as volume and frequency of consumption or treatment retention) was unclear.[86]​ It was also uncertain whether adding psychosocial therapy gave benefit compared with pharmacologic treatment alone. Most studies have evaluated CBT adjunctive to naltrexone, in people without comorbid mental health or substance use disorder.[86]

2nd line – acamprosate

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alcohol use disorder: nonpregnant adult with no concurrent opioid use or mental health diagnosis
2nd line – 

acamprosate

Acamprosate normalizes 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 metabolized 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.[97][98]​ 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 number needed to treat is 11 to prevent return to any drinking.[94]​ Diarrhea is a common adverse effect.[94]

Naltrexone and acamprosate are considered to be equally efficacious, with both supported as first-choice pharmacotherapy options by guidance and evidence.[51][94][96]​ However, guideline groups are unanimous in emphasizing the importance of informed patient choice, with patient preferences and care needs central to treatment planning.[3][42][51]​ Pill burden may reduce the effectiveness of acamprosate, and can limit its use in clinical practice.

It is suggested that drugs are continued for at least 6 months due to the chronic, relapsing nature of the condition.[75]​ Further treatment is determined through shared decision-making.

Primary options

acamprosate: 666 mg orally three times daily

Plus – management of medical comorbidities

Back
ONGOING
|
alcohol use disorder: nonpregnant adult with no concurrent opioid use or mental health diagnosis
Plus – 

management of medical comorbidities

Treatment recommended for ALL patients in selected patient group

Patients with unhealthy alcohol use often have coexisting high blood pressure, insomnia, weight gain, cognitive disturbances, gastrointestinal distress, and cardiac arrhythmias. It is important to emphasize 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][111]​ Chronic care management reduces harms of alcohol use disorder in patients with medical comorbidities.[112]​ Treatment programs should have provision for external referral to medical services when indicated.[3]

Consider – psychosocial treatment

Back
ONGOING
|
alcohol use disorder: nonpregnant adult with no concurrent opioid use or mental health diagnosis
Consider – 

psychosocial treatment

Treatment recommended for SOME patients in selected patient group

The use of pharmacologic treatment does not preclude other psychosocial support; and psychosocial support does not preclude the use of pharmacologic treatment. Indeed, the greatest efficacy may be seen in patients using a combination of pharmacotherapy and psychosocial treatment.[75]​ However, the patient’s decision to decline psychosocial treatment should not preclude or delay pharmacotherapy.[3]

When provided alongside pharmacologic treatment or other first-line psychosocial interventions, the Department of Veterans Affairs /Department of Defense report evidence to support options of cognitive behavioral therapy (CBT), Motivational Enhancement Therapy (MET) or 12-Step Facilitation of programs such as Alcoholics Anonymous.[42]​ MET strategies, in particular, have been recognized to encourage engagement and retention in care.[3]

One Cochrane systematic review found moderate-certainty evidence that, compared with psychosocial therapy alone, adding pharmacologic treatment was safe and reduced the number of "heavy drinkers", but an effect on other outcomes (such as volume and frequency of consumption or treatment retention) was unclear.[86]​ It was also uncertain whether adding psychosocial therapy gave benefit compared with pharmacologic treatment alone. Most studies have evaluated CBT adjunctive to naltrexone, in people without comorbid mental health or substance use disorder.[86]

2nd line – topiramate

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alcohol use disorder: nonpregnant adult with no concurrent opioid use or mental health diagnosis
2nd line – 

topiramate

Topiramate is an anticonvulsant that has been shown in randomized controlled trials to decrease craving and withdrawal symptoms and significantly improve physical and psychosocial well-being of patients with alcohol use disorder, compared with placebo.​​​​[102][103][104][105][106]​​​​[131][132]

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.[94]​​ Importantly, efficacy has been established in subjects who were drinking at the time of starting the drug.[107]​ 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.[108]​

The benefits of topiramate should be weighed against the number needed to harm given its high side effect profile, including blurred vision, paresthesias, poor memory, and loss of coordination.[94]​ Topiramate has been poorly tolerated in clinical trials, causing twice as many dropouts due to adverse effects as placebo.[96]​​

In some countries, topiramate is contraindicated in women of childbearing age unless the conditions of a pregnancy prevention program are fulfilled.[118][120]

Use in clinical practice may not always reflect this suggested position in care; guideline groups are unanimous in emphasizing the importance of informed patient choice, with patient preferences and care needs central to treatment planning.[3][42][51]

It is suggested that drugs are continued for at least 6 months due to the chronic, relapsing nature of the condition.[75]​ Further treatment is determined through shared decision-making.​

Primary options

topiramate: 100-150 mg orally (immediate-release) twice daily

Plus – management of medical comorbidities

Back
ONGOING
|
alcohol use disorder: nonpregnant adult with no concurrent opioid use or mental health diagnosis
Plus – 

management of medical comorbidities

Treatment recommended for ALL patients in selected patient group

Patients with unhealthy alcohol use often have coexisting high blood pressure, insomnia, weight gain, cognitive disturbances, gastrointestinal distress, and cardiac arrhythmias. It is important to emphasize 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][111]​ Chronic care management reduces harms of alcohol use disorder in patients with medical comorbidities.​[112]​ Treatment programs should have provision for external referral to medical services when indicated.[3]

Consider – psychosocial treatment

Back
ONGOING
|
alcohol use disorder: nonpregnant adult with no concurrent opioid use or mental health diagnosis
Consider – 

psychosocial treatment

Treatment recommended for SOME patients in selected patient group

​The use of pharmacologic treatment does not preclude other psychosocial support; and psychosocial support does not preclude the use of pharmacologic treatment. Indeed, the greatest efficacy may be seen in patients using a combination of pharmacotherapy and psychosocial treatment.[75]​ However, the patient’s decision to decline psychosocial treatment should not preclude or delay pharmacotherapy.[3]

When provided alongside pharmacologic treatment or other first-line psychosocial interventions, the Department of Veterans Affairs /Department of Defense report evidence to support options of cognitive behavioral therapy (CBT), Motivational Enhancement Therapy (MET) or 12-Step Facilitation of programs such as Alcoholics Anonymous.[42]​ MET strategies, in particular, have been recognized to encourage engagement and retention in care.[3]​

One Cochrane systematic review found moderate-certainty evidence that, compared with psychosocial therapy alone, adding pharmacologic treatment was safe and reduced the number of "heavy drinkers", but an effect on other outcomes (such as volume and frequency of consumption or treatment retention) was unclear.[86]​ It was also uncertain whether adding psychosocial therapy gave benefit compared with pharmacologic treatment alone. Most studies have evaluated CBT adjunctive to naltrexone, in people without comorbid mental health or substance use disorder.[86]

2nd line – gabapentin

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ONGOING
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alcohol use disorder: nonpregnant adult with no concurrent opioid use or mental health diagnosis
2nd line – 

gabapentin

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 randomized controlled trial (RCT) of 96 individuals with alcohol use disorder, gabapentin resulted in a statistically significant decrease in heavy drinking days (number needed to treat [NNT] 5) and prevented return to use (NNT 6) for patients with high baseline alcohol withdrawal symptoms.[99]​ However, the largest RCT to date (346 patients), which used the extended-release formulation, found no benefit compared with placebo.[100]​ Meta-analyses have concluded a low strength of evidence for gabapentin overall, with any effects on drinking outcomes being of only borderline statistical significance.[94][96]​​ 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.​[101]​​​​​ The main side effects of gabapentin are dizziness, drowsiness, and nausea. Patients should be counseled that abrupt cessation of gabapentin can lower the seizure threshold.​

Use in clinical practice may not always reflect this suggested position in care; guideline groups are unanimous in emphasizing the importance of informed patient choice, with patient preferences and care needs central to treatment planning.[3][42][51]

It is suggested that drugs are continued for at least 6 months due to the chronic, relapsing nature of the condition.[75]​ Further treatment is determined through shared decision-making.​

Primary options

gabapentin: 300-600 mg orally three times daily

Plus – management of medical comorbidities

Back
ONGOING
|
alcohol use disorder: nonpregnant adult with no concurrent opioid use or mental health diagnosis
Plus – 

management of medical comorbidities

Treatment recommended for ALL patients in selected patient group

Patients with unhealthy alcohol use often have coexisting high blood pressure, insomnia, weight gain, cognitive disturbances, gastrointestinal distress, and cardiac arrhythmias. It is important to emphasize 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][111]​ Chronic care management reduces harms of alcohol use disorder in patients with medical comorbidities.​[112]​ ​​Treatment programs should have provision for external referral to medical services when indicated.[3]

Consider – psychosocial treatment

Back
ONGOING
|
alcohol use disorder: nonpregnant adult with no concurrent opioid use or mental health diagnosis
Consider – 

psychosocial treatment

Treatment recommended for SOME patients in selected patient group

The use of pharmacologic treatment does not preclude other psychosocial support; and psychosocial support does not preclude the use of pharmacologic treatment. Indeed, the greatest efficacy may be seen in patients using a combination of pharmacotherapy and psychosocial treatment.[75]​​ ​

When provided alongside pharmacologic treatment or other first-line psychosocial interventions, the Department of Veterans Affairs /Department of Defense report evidence to support options of cognitive behavioral therapy (CBT), Motivational Enhancement Therapy (MET) or 12-Step Facilitation of programs such as Alcoholics Anonymous.[42]​ MET strategies, in particular, have been recognized to encourage engagement and retention in care.[3]

One Cochrane systematic review found moderate-certainty evidence that, compared with psychosocial therapy alone, adding pharmacologic treatment was safe and reduced the number of "heavy drinkers", but an effect on other outcomes (such as volume and frequency of consumption or treatment retention) was unclear.[86]​ It was also uncertain whether adding psychosocial therapy gave benefit compared with pharmacologic treatment alone. Most studies have evaluated CBT adjunctive to naltrexone, in people without comorbid mental health or substance use disorder.[86]

3rd line – disulfiram

Back
ONGOING
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alcohol use disorder: nonpregnant adult with no concurrent opioid use or mental health diagnosis
3rd line – 

disulfiram

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, diarrhea), 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 randomized controlled trials (RCTs); a finding supported by subsequent network meta-analysis.[96][109]​​ However, meta-analyses limited to blinded RCTs have not demonstrated a benefit of disulfiram.[94][109] 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.[109]​ ​

Use in clinical practice may not always reflect this suggested position in care; guideline groups are unanimous in emphasizing the importance of informed patient choice, with patient preferences and care needs central to treatment planning.[3][42][51]​​

It is suggested that drugs are continued for at least 6 months due to the chronic, relapsing nature of the condition.[75]​ Further treatment is determined through shared decision-making.

Primary options

disulfiram: 125-500 mg orally once daily in the morning

Plus – management of medical comorbidities

Back
ONGOING
|
alcohol use disorder: nonpregnant adult with no concurrent opioid use or mental health diagnosis
Plus – 

management of medical comorbidities

Treatment recommended for ALL patients in selected patient group

Patients with unhealthy alcohol use often have coexisting high blood pressure, insomnia, weight gain, cognitive disturbances, gastrointestinal distress, and cardiac arrhythmias. It is important to emphasize 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][111]​ Chronic care management reduces harms of alcohol use disorder in patients with medical comorbidities.​[112] Treatment programs should have provision for external referral to medical services when indicated.[3]

Consider – psychosocial treatment

Back
ONGOING
|
alcohol use disorder: nonpregnant adult with no concurrent opioid use or mental health diagnosis
Consider – 

psychosocial treatment

Treatment recommended for SOME patients in selected patient group

The use of pharmacologic treatment does not preclude other psychosocial support; and psychosocial support does not preclude the use of pharmacologic treatment. Indeed, the greatest efficacy may be seen in patients using a combination of pharmacotherapy and psychosocial treatment.[75]​​ However, the patient’s decision to decline psychosocial treatment should not preclude or delay pharmacotherapy.[3]

When provided alongside pharmacologic treatment or other first-line psychosocial interventions, the Department of Veterans Affairs /Department of Defense report evidence to support options of cognitive behavioral therapy (CBT), Motivational Enhancement Therapy (MET) or 12-Step Facilitation of programs such as Alcoholics Anonymous.[42]​ MET strategies, in particular, have been recognized to encourage engagement and retention in care.[3]

One Cochrane systematic review found moderate-certainty evidence that, compared with psychosocial therapy alone, adding pharmacologic treatment was safe and reduced the number of "heavy drinkers", but an effect on other outcomes (such as volume and frequency of consumption or treatment retention) was unclear.[86]​ It was also uncertain whether adding psychosocial therapy gave benefit compared with pharmacologic treatment alone. Most studies have evaluated CBT adjunctive to naltrexone, in people without comorbid mental health or substance use disorder.[86]

alcohol use disorder: nonpregnant adult with concurrent opioid use

1st line – psychosocial treatment

Back
ONGOING
|
alcohol use disorder: nonpregnant adult with concurrent opioid use
1st line – 

psychosocial treatment

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 pharmacologic therapies for alcohol and drug use disorders.[124][125]​​ These procedures include patient education, personalized feedback, emotional support, drug monitoring, and motivational enhancement. National Institute on Alcohol Abuse and Alcoholism (NIAAA) Opens in new window

1st line – acamprosate

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ONGOING
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alcohol use disorder: nonpregnant adult with concurrent opioid use
1st line – 

acamprosate

​Acamprosate normalizes 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. Pill burden may reduce its effectiveness. It is primarily metabolized 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 has been shown to increase the rate and duration of abstinence compared with placebo, in general patient populations (not specific to those with concurrent opioid use).[97][98]​​​ Acamprosate is safe to use in patients who are actively drinking, but evidence for its use is from trials with people who have already stopped drinking. In meta-analysis (not specific to those with concurrent opioid use), the number needed to treat is 11 to prevent return to any drinking.[94]​ Diarrhea is a common adverse effect.[94]​​ 

It is suggested that drugs are continued for at least 6 months due to the chronic, relapsing nature of the condition.[75]​ Further treatment is determined through shared decision-making.

Primary options

acamprosate: 666 mg orally three times daily

Consider – psychosocial treatment

Back
ONGOING
|
alcohol use disorder: nonpregnant adult with concurrent opioid use
Consider – 

psychosocial treatment

Treatment recommended for SOME patients in selected patient group

The use of pharmacologic treatment does not preclude other psychosocial support; and psychosocial support does not preclude the use of pharmacologic treatment. Indeed, the greatest efficacy may be seen in patients using a combination of pharmacotherapy and psychosocial treatment.[75]​​ However, the majority of studies evaluating combined pharmacologic and psychosocial interventions for alcohol use disorder have been conducted in patients without concurrent substance use disorder.[86]​ ​​​

1st line – gabapentin

Back
ONGOING
|
alcohol use disorder: nonpregnant adult with concurrent opioid use
1st line – 

gabapentin

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 a randomized controlled trial (RCT) of 96 individuals with alcohol use disorder, gabapentin resulted in a statistically significant decrease in heavy drinking days (number needed to treat [NNT] 5) and prevented return to use (NNT 6) for patients with high baseline alcohol withdrawal symptoms.[99]​ The largest RCT to date (346 patients), which used the extended-release formulation, found no benefit compared with placebo.[100]​ However, these trials excluded people with concurrent opioid use disorder, so evidence applicability is uncertain. Meta-analyses (not specific to patients with concurrent opioid use) have concluded a low strength of evidence for gabapentin overall, with any effects on drinking outcomes being of only borderline statistical significance.[94][96]​ Nevertheless, it may be an effective option in patients with symptoms of alcohol withdrawal, or when other drugs are contraindicated or poorly tolerated.[42][51]​​​​​​ The main side effects of gabapentin are dizziness, drowsiness, and nausea. Patients should be counseled that abrupt cessation of gabapentin can lower the seizure threshold.​

Evidence indicates that patients with opioid use disorder and polydrug users are at risk for gabapentin misuse and clinicians should monitor usage closely.[126]

It is suggested that drugs are continued for at least 6 months due to the chronic, relapsing nature of the condition.[75]​ Further treatment is determined through shared decision-making.​

Primary options

gabapentin: 300-600 mg orally three times daily

Consider – psychosocial treatment

Back
ONGOING
|
alcohol use disorder: nonpregnant adult with concurrent opioid use
Consider – 

psychosocial treatment

Treatment recommended for SOME patients in selected patient group

The use of pharmacologic treatment does not preclude other psychosocial support; and psychosocial support does not preclude the use of pharmacologic treatment. Indeed, the greatest efficacy may be seen in patients using a combination of pharmacotherapy and psychosocial treatment.[75]​ However, the majority of studies evaluating combined pharmacologic and psychosocial interventions for alcohol use disorder have been conducted in patients without concurrent substance use disorder.[86]

2nd line – topiramate

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ONGOING
|
alcohol use disorder: nonpregnant adult with concurrent opioid use
2nd line – 

topiramate

Topiramate is an anticonvulsant that has been shown in randomized controlled trials to decrease craving and withdrawal symptoms and significantly improve physical and psychosocial well-being of patients with alcohol use disorder, compared with placebo.​[102][103][104][105][106][131]​​​​[132]​

​In meta-analysis (not specific to patients with concurrent opioid use) 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.[94]​​ Importantly, efficacy has been established in subjects who were drinking at the time of starting the drug.[107]​ 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.[108]​

The benefits of topiramate should be weighed against the number needed to harm given its high side effect profile, including blurred vision, paresthesias, poor memory, and loss of coordination.[94]​ Topiramate has been poorly tolerated in clinical trials, causing twice as many dropouts due to adverse effects as placebo.[96]

In some countries, topiramate is contraindicated in women of childbearing age unless the conditions of a pregnancy prevention program are fulfilled.[118][120]​​​

It is suggested that drugs are continued for at least 6 months due to the chronic, relapsing nature of the condition.[75]​ Further treatment is determined through shared decision-making.​

Primary options

topiramate: 100-150 mg orally (immediate-release) twice daily

Consider – psychosocial treatment

Back
ONGOING
|
alcohol use disorder: nonpregnant adult with concurrent opioid use
Consider – 

psychosocial treatment

Treatment recommended for SOME patients in selected patient group

The use of pharmacologic treatment does not preclude other psychosocial support; and psychosocial support does not preclude the use of pharmacologic treatment. Indeed, the greatest efficacy may be seen in patients using a combination of pharmacotherapy and psychosocial treatment.[75]​ ​​However, the majority of studies evaluating combined pharmacologic and psychosocial interventions for alcohol use disorder have been conducted in patients without coexisting substance use disorder.[86]

2nd line – disulfiram

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alcohol use disorder: nonpregnant adult with concurrent opioid use
2nd line – 

disulfiram

​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, diarrhea), headache, respiratory depression, and malaise. These symptoms are generally transient, but serious reactions may occur that require urgent medical treatment. Due to hepatotoxicity, it 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 (not specific to patients with concurrent opioid use) showed that disulfiram was more effective than placebo, acamprosate or naltrexone in open-label randomized controlled trials (RCTs); a finding supported by subsequent network meta-analysis.[96][109]​ However, meta-analyses limited to blinded RCTs have not demonstrated a benefit of disulfiram.[94][109]​​ 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.[109]​ ​

It is suggested that drugs are continued for at least 6 months due to the chronic, relapsing nature of the condition.[75]​ Further treatment is determined through shared decision-making.​

Primary options

disulfiram: 125-500 mg orally once daily in the morning

Consider – psychosocial treatment

Back
ONGOING
|
alcohol use disorder: nonpregnant adult with concurrent opioid use
Consider – 

psychosocial treatment

Treatment recommended for SOME patients in selected patient group

The use of pharmacologic treatment does not preclude other psychosocial support; and psychosocial support does not preclude the use of pharmacologic treatment. Indeed, the greatest efficacy may be seen in patients using a combination of pharmacotherapy and psychosocial treatment.[75]​​ However, the majority of studies evaluating combined pharmacologic and psychosocial interventions for alcohol use disorder have been conducted in patients without coexisting substance use disorder.[86]

alcohol use disorder: nonpregnant adult with concurrent mental health diagnosis

1st line – psychosocial treatment

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ONGOING
|
alcohol use disorder: nonpregnant adult with concurrent mental health diagnosis
1st line – 

psychosocial treatment

​Nonpharmacologic 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][83][84]​​ Although notably, 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.[84]

The Department of Veterans Affairs/Department of Defense suggests the following as first-line options that have demonstrated modest effect on alcohol consumption and recovery: cognitive behavioral therapy (CBT, assists patients in coping with thoughts of return to alcohol use and negative cognitions); behavioral couples therapy (BCT, aims to improve relationship functioning with goals to reduce alcohol use with partner support); community reinforcement approach (CRA, comprehensive cognitive behavioral approach that addresses environmental contingencies that influence drinking behavior); motivational enhancement therapy (MET, based on the principles of motivational interviewing but using a structured, individualized plan incorporating assessment and feedback to enhance self-efficacy); and 12-step facilitation (TSF, systematized approach that aims to enhance engagement in Alcoholics Anonymous [AA] or other 12-step based self-help groups).[42]

Outpatient and intensive outpatient treatment programs 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 program. Its primary goal is to help individuals maintain total abstinence from alcohol and other addictive substances. Alcoholics Anonymous Opens in new window [ Cochrane Clinical Answers logo ] [Evidence A]​​​​​​ Self-help programs 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 randomized controlled trial, AA improved drinking outcomes, largely through improvements in adaptive social network changes and social self-efficacy.[85]​ 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.

Reassess every 3 months for worsening use or harms of alcohol.

Plus – management of mental health diagnoses

Back
ONGOING
|
alcohol use disorder: nonpregnant adult with concurrent mental health diagnosis
Plus – 

management of mental health diagnoses

Treatment recommended for ALL patients in selected patient group

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.

One meta-analysis of 15 randomized controlled trials demonstrated reduced alcohol use and improved psychiatric outcomes when co-occurring depressive and anxiety disorders were treated concurrently with alcohol use disorder.[127]

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.[128]​ Trials of fluoxetine for alcohol use disorder achieved similar results, suggesting that fluoxetine may also be effective in mild alcohol use disorder.[129]​ 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.[130]

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

Treatment programs 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.

1st line – naltrexone

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ONGOING
|
alcohol use disorder: nonpregnant adult with concurrent mental health diagnosis
1st line – 

naltrexone

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.[88] It is available in oral and intramuscular formulations. It is particularly useful in patients with a family history of alcohol use disorder and in those with significant alcohol cravings.[16][51][89]​​

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.[90][91][92]​​​​​

In one randomized controlled trial (which excluded patients with comorbid psychiatric disorder requiring drug treatment), naltrexone reduced heavy drinking days, increased abstinence, and reduced the risk of returning to any or heavy drinking at 3 and 12 months post-treatment, compared with placebo.[93] [ Cochrane Clinical Answers logo ] ​​​​​​​ In one meta-analysis of 118 studies (not specific to patients with comorbid mental health diagnosis), 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.[94]​​ The intramuscular formulation of naltrexone may be more effective in patients with difficulty taking daily drug therapy, with some evidence that it can reduce percentage drinking days (5% reduction vs. placebo).[94][95]​ Naltrexone can be used as a monotherapy or in combination with gabapentin, topiramate, acamprosate, or disulfiram (unless specific drugs are contraindicated).

It is suggested that drugs are continued for 6 months due to the chronic, relapsing nature of the condition.[75]​ Further treatment is determined through shared decision-making.

Primary options

naltrexone: 50 mg orally once daily; 380 mg intramuscularly every 4 weeks

Plus – management of mental health diagnoses

Back
ONGOING
|
alcohol use disorder: nonpregnant adult with concurrent mental health diagnosis
Plus – 

management of mental health diagnoses

Treatment recommended for ALL patients in selected patient group

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.

One meta-analysis of 15 randomized controlled trials demonstrated reduced alcohol use and improved psychiatric outcomes when co-occurring depressive and anxiety disorders were treated concurrently with alcohol use disorder.[127]

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.[128]​ Trials of fluoxetine for alcohol use disorder achieved similar results, suggesting that fluoxetine may also be effective in mild alcohol use disorder.[129]​ 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.[130]

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

Treatment programs 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.

2nd line – acamprosate

Back
ONGOING
|
alcohol use disorder: nonpregnant adult with concurrent mental health diagnosis
2nd line – 

acamprosate

Acamprosate normalizes 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 metabolized 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 has been shown to increase the rate and duration of abstinence compared with placebo, though notably these analyses excluded patients with comorbid mental health diagnosis.[97][98]

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 (not specific to patients with comorbid mental health diagnosis), the number needed to treat is 11 to prevent return to any drinking.[94]​ Diarrhea is a common adverse effect.[94]​ Pill burden may also reduce the effectiveness of acamprosate, and can limit its use in clinical practice.

It is suggested that drugs are continued for at least 6 months due to the chronic, relapsing nature of the condition.[75]​ Further treatment is determined through shared decision-making.

Primary options

acamprosate: 666 mg orally three times daily

Plus – management of mental health diagnoses

Back
ONGOING
|
alcohol use disorder: nonpregnant adult with concurrent mental health diagnosis
Plus – 

management of mental health diagnoses

Treatment recommended for ALL patients in selected patient group

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.

One meta-analysis of 15 randomized controlled trials demonstrated reduced alcohol use and improved psychiatric outcomes when co-occurring depressive and anxiety disorders were treated concurrently with alcohol use disorder.[127]

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.[128]​ Trials of fluoxetine for alcohol use disorder achieved similar results, suggesting that fluoxetine may also be effective in mild alcohol use disorder.[129]​ 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.[130]

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

Treatment programs 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.

2nd line – gabapentin

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ONGOING
|
alcohol use disorder: nonpregnant adult with concurrent mental health diagnosis
2nd line – 

gabapentin

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 randomized controlled trial (RCT) of 96 individuals with alcohol use disorder, gabapentin resulted in a statistically significant decrease in heavy drinking days (number needed to treat [NNT] 5) and prevented return to use (NNT 6) for patients with high baseline alcohol withdrawal symptoms.[99]​ The largest RCT to date (346 patients), which used the extended-release formulation, found no benefit compared with placebo.[100]​ However, these trials excluded patients with comorbid major psychiatric disorder, so evidence applicability is uncertain. 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]​​​​

The main side effects of gabapentin are dizziness, drowsiness, and nausea. Patients should be counseled that abrupt cessation of gabapentin can lower the seizure threshold.

It is suggested that drugs are continued for 6 months due to the chronic, relapsing nature of the condition.[75]​ Further treatment is determined through shared decision-making.

Primary options

gabapentin: 300-600 mg orally three times daily

Plus – management of mental health diagnoses

Back
ONGOING
|
alcohol use disorder: nonpregnant adult with concurrent mental health diagnosis
Plus – 

management of mental health diagnoses

Treatment recommended for ALL patients in selected patient group

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.

One meta-analysis of 15 randomized controlled trials demonstrated reduced alcohol use and improved psychiatric outcomes when co-occurring depressive and anxiety disorders were treated concurrently with alcohol use disorder.[127]

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.[128]​ Trials of fluoxetine for alcohol use disorder achieved similar results, suggesting that fluoxetine may also be effective in mild alcohol use disorder.[129]​ 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.[130]

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

Treatment programs 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.

2nd line – topiramate

Back
ONGOING
|
alcohol use disorder: nonpregnant adult with concurrent mental health diagnosis
2nd line – 

topiramate

Topiramate is an anticonvulsant that has been shown in randomized controlled trials to decrease craving and withdrawal symptoms and significantly improve physical and psychosocial well-being of patients with alcohol use disorder, compared with placebo.​[102][103][104][105][106][131]​​​​[132]

In meta-analysis (not specific to patients with comorbid mental health diagnosis) 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.[94]​​ Importantly, efficacy has been established in subjects who were drinking at the time of starting the drug.[107]​ 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.[108]​

The benefits of topiramate should be weighed against the number needed to harm given its high side effect profile, including blurred vision, paresthesias, poor memory, and loss of coordination.[94]​ Topiramate has been poorly tolerated in clinical trials, causing twice as many dropouts due to adverse effects as placebo.[96]

In some countries, topiramate is contraindicated in women of childbearing age unless the conditions of a pregnancy prevention program are fulfilled.[118][120]​​​

It is suggested that drugs are continued for 6 months due to the chronic, relapsing nature of the condition.[75]​ Further treatment is determined through shared decision-making.

Primary options

topiramate: 100-150 mg orally (immediate-release) twice daily

Plus – management of mental health diagnoses

Back
ONGOING
|
alcohol use disorder: nonpregnant adult with concurrent mental health diagnosis
Plus – 

management of mental health diagnoses

Treatment recommended for ALL patients in selected patient group

​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.

One meta-analysis of 15 randomized controlled trials demonstrated reduced alcohol use and improved psychiatric outcomes when co-occurring depressive and anxiety disorders were treated concurrently with alcohol use disorder.[127]

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.[128]​ Trials of fluoxetine for alcohol use disorder achieved similar results, suggesting that fluoxetine may also be effective in mild alcohol use disorder.[129]​ 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.[130]

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

Treatment programs 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.

3rd line – disulfiram

Back
ONGOING
|
alcohol use disorder: nonpregnant adult with concurrent mental health diagnosis
3rd line – 

disulfiram

​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, diarrhea), headache, respiratory depression, and malaise. These symptoms are generally transient, but serious reactions may occur that require urgent medical treatment. Due to hepatotoxicity, it 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 (not specific to patients with comorbid mental health diagnosis) showed that disulfiram was more effective than placebo, acamprosate or naltrexone in open-label randomized controlled trials (RCTs); a finding supported by subsequent network meta-analysis.[96][109]​ However, meta-analyses limited to blinded RCTs have not demonstrated a benefit of disulfiram.[94][109] 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.[109]​ 

It is suggested that drugs are continued for 6 months due to the chronic, relapsing nature of the condition.[75]​ Further treatment is determined through shared decision-making.

Primary options

disulfiram: 125-500 mg orally once daily in the morning

Plus – management of mental health diagnoses

Back
ONGOING
|
alcohol use disorder: nonpregnant adult with concurrent mental health diagnosis
Plus – 

management of mental health diagnoses

Treatment recommended for ALL patients in selected patient group

​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.

One meta-analysis of 15 randomized controlled trials demonstrated reduced alcohol use and improved psychiatric outcomes when co-occurring depressive and anxiety disorders were treated concurrently with alcohol use disorder.[127]

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.[128]​ Trials of fluoxetine for alcohol use disorder achieved similar results, suggesting that fluoxetine may also be effective in mild alcohol use disorder.[129]​ 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.[130]

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

Treatment programs 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.

alcohol use disorder: nonpregnant adolescent

1st line – psychosocial treatment

Back
ONGOING
|
alcohol use disorder: nonpregnant adolescent
1st line – 

psychosocial treatment

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 behavioral therapy with 12 steps, cognitive behavioral therapy with aftercare, multidimensional family therapy, brief interventions with the adolescent, and brief interventions with the adolescent and a parent.[121]

Group therapy-based treatments may be effective for adolescents, but safety should be considered and these modalities require further investigation.[122]​

1st line – naltrexone

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ONGOING
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alcohol use disorder: nonpregnant adolescent
1st line – 

naltrexone

Naltrexone is the best studied drug treatment to support reduced alcohol intake and abstinence in adolescents, and has been found to reduce cravings in adolescents in a few small trials.[123]​ 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.

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.[88] It is available in oral and intramuscular formulations. It is particularly useful in patients with a family history of alcohol use disorder and in those with significant alcohol cravings.[16][51][89]​​

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.[90][91][92]​​​​​

One randomized controlled trial (RCT; in a majority adult population) found that naltrexone reduced heavy drinking days, increased abstinence, and reduced the risk of returning to any or heavy drinking at 3 and 12 months post-treatment, compared with placebo.[93] [ Cochrane Clinical Answers logo ] ​​​​​​​ In one meta-analysis of 118 RCTs in adults (ages <18 years excluded), 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.[94]​​ The intramuscular formulation of naltrexone may be more effective in patients with difficulty taking daily drug therapy, with some evidence that it can reduce percentage drinking days (5% reduction vs. placebo).[94][95]​ 

It is suggested that drugs are continued for 6 months due to the chronic, relapsing nature of the condition.[75]​ Further treatment is determined through shared decision-making. 

Primary options

naltrexone: 50 mg orally once daily; 380 mg intramuscularly every 4 weeks

Consider – psychosocial treatment

Back
ONGOING
|
alcohol use disorder: nonpregnant adolescent
Consider – 

psychosocial treatment

Treatment recommended for SOME patients in selected patient group

​The use of pharmacologic treatment does not preclude other psychosocial support; and psychosocial support does not preclude the use of pharmacologic treatment. Indeed, the greatest efficacy may be seen in patients using a combination of pharmacotherapy and psychosocial treatment.[75]​​ However, the patient’s decision to decline psychosocial treatment should not preclude or delay pharmacotherapy.[3]

2nd line – acamprosate

Back
ONGOING
|
alcohol use disorder: nonpregnant adolescent
2nd line – 

acamprosate

Acamprosate is an alternative option. 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.

Acamprosate normalizes 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. Pill burden may reduce its effectiveness. It is primarily metabolized 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 has been shown to increase the rate and duration of abstinence compared with placebo, though notably most studies have excluded patient ages <18 years.[97][98]​​​ Acamprosate is safe to use in patients who are actively drinking, but evidence for its use is from trials with people who have already stopped drinking. Meta-analysis in adults (ages <18 years excluded) found the number needed to treat is 11 to prevent return to any drinking.[94] Diarrhea is a common adverse effect.[94]​​​ 

It is suggested that drugs are continued for at least 6 months due to the chronic, relapsing nature of the condition.[75]​ Further treatment is determined through shared decision-making.

Primary options

acamprosate: 666 mg orally three times daily

Consider – psychosocial treatment

Back
ONGOING
|
alcohol use disorder: nonpregnant adolescent
Consider – 

psychosocial treatment

Treatment recommended for SOME patients in selected patient group

​The use of pharmacologic treatment does not preclude other psychosocial support; and psychosocial support does not preclude the use of pharmacologic treatment. Indeed, the greatest efficacy may be seen in patients using a combination of drug therapy and psychosocial treatment.[75]​​ However, the patient’s decision to decline psychosocial treatment should not preclude or delay pharmacotherapy.[3]

alcohol use disorder: pregnant

1st line – psychosocial treatment

Back
ONGOING
|
alcohol use disorder: pregnant
1st line – 

psychosocial treatment

​​Systematic review evidence shows that psychosocial interventions may increase abstinence rates, compared with usual care or no intervention, in pregnant women who consume alcohol.​[113][114]​​ 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.[114]​

Guidance (not specific to pregnant populations) states there is no strong evidence for any one approach, and therefore patient preference and local availability should guide treatment choice.[42][83][84]​​​

The Department of Veterans Affairs/Department of Defense suggests the following as first-line options that have demonstrated modest effect on alcohol consumption and recovery: cognitive behavioral therapy (CBT, assists patients in coping with thoughts of return to alcohol use and negative cognitions); behavioral couples therapy (BCT, aims to improve relationship functioning with goals to reduce alcohol use with partner support); community reinforcement approach (CRA, comprehensive cognitive behavioral approach that addresses environmental contingencies that influence drinking behavior); motivational enhancement therapy (MET, based on the principles of motivational interviewing but using a structured, individualized plan incorporating assessment and feedback to enhance self-efficacy); and 12-step facilitation (TSF, systematized approach that aims to enhance engagement in Alcoholics Anonymous [AA] or other 12-step based self-help groups).[42]

Outpatient and intensive outpatient addiction treatment programs 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 program. Its primary goal is to help individuals maintain total abstinence from alcohol and other addictive substances. Alcoholics Anonymous Opens in new window [ Cochrane Clinical Answers logo ] [Evidence A]​​​​​​​ Self-help programs 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 randomized controlled trial, AA improved drinking outcomes, largely through improvements in adaptive social network changes and social self-efficacy.[85]​ 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.

Reassess every 3 months for worsening use or harms of alcohol.

1st line – naltrexone

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alcohol use disorder: pregnant
1st line – 

naltrexone

There are no randomized controlled trials evaluating the effectiveness of pharmacologic interventions to reduce alcohol use or improve maternal, birth, and infant outcomes in pregnant women who consume alcohol or with alcohol use disorder.[114][115]​​ 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, drug treatment may still be considered for women who are unable to stop drinking without pharmacologic support. 

Naltrexone is the best-studied in pregnant patients, although primarily in opioid use disorder, and is not associated with birth defects.[116]​ It is generally recommended to switch to the oral formulation at 36 weeks’ gestation to allow for effective pain management at birth. 

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.[88] It is available in oral and intramuscular formulations. It is particularly useful in patients with a family history of alcohol use disorder and in those with significant alcohol cravings.[16][51][89]​​

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.[90][91][92]​​​​​​

One randomized controlled trial (not specific to pregnant patients) found that naltrexone reduced heavy drinking days, increased abstinence, and reduced the risk of returning to any or heavy drinking at 3 and 12 months post-treatment, compared with placebo.[93] [ Cochrane Clinical Answers logo ] ​​​​​​​​​ In one meta-analysis of 118 studies (not specific to pregnant patients), 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.[94]​​ The intramuscular formulation of naltrexone may be more effective in patients with difficulty taking daily drug therapy, with some evidence that it can reduce percentage drinking days (5% reduction vs. placebo).[94][95]

It is suggested that drugs are continued for at least 6 months due to the chronic, relapsing nature of the condition.[75]​ Further treatment is determined through shared decision-making.

Primary options

naltrexone: 50 mg orally once daily; 380 mg intramuscularly every 4 weeks

Consider – psychosocial treatment

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alcohol use disorder: pregnant
Consider – 

psychosocial treatment

Treatment recommended for SOME patients in selected patient group

​The use of pharmacologic treatment does not preclude other psychosocial support; and psychosocial support does not preclude the use of pharmacologic treatment. Indeed, the greatest efficacy may be seen in patients using a combination of pharmacotherapy and psychosocial treatment.[75] However, the patient’s decision to decline psychosocial treatment should not preclude or delay pharmacotherapy.[3]​​​ ​​

2nd line – gabapentin

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alcohol use disorder: pregnant
2nd line – 

gabapentin

​There are no randomized controlled trials (RCTs) evaluating the effectiveness of pharmacologic interventions to reduce alcohol use or improve maternal, birth, and infant outcomes in pregnant women who consume alcohol or with alcohol use disorder.[114][115]​ 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, drug treatment may still be considered for women who are unable to stop drinking without pharmacologic support. 

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

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 (which excluded pregnant patients), gabapentin resulted in a statistically significant decrease in heavy drinking days (number needed to treat [NNT] 5) and preventing return to use (NNT 6) for patients with high baseline alcohol withdrawal symptoms.[99]​ However, the largest RCT to date in 346 individuals (pregnancy eligibility not specified) found no benefit of the extended-release formulation compared with placebo.[100]​ Meta-analyses (not specific to pregnant patients) have concluded a low strength of evidence for gabapentin overall, with any effects on drinking outcomes being of only borderline statistical significance.[94][96]​ Nevertheless, it may be an effective option in patients with symptoms of alcohol withdrawal, or when other drugs are contraindicated or poorly tolerated.[42][51]​​​​​​​

The main side effects of gabapentin are dizziness, drowsiness, and nausea. Patients should be counseled that abrupt cessation of gabapentin can lower the seizure threshold.

It is suggested that drugs are continued for at least 6 months due to the chronic, relapsing nature of the condition.[75]​ Further treatment is determined through shared decision-making.

Primary options

gabapentin: 300-600 mg orally three times daily

Consider – psychosocial treatment

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ONGOING
|
alcohol use disorder: pregnant
Consider – 

psychosocial treatment

Treatment recommended for SOME patients in selected patient group

​The use of pharmacologic treatment does not preclude other psychosocial support; and psychosocial support does not preclude the use of pharmacologic treatment. Indeed, the greatest efficacy may be seen in patients using a combination of pharmacotherapy and psychosocial treatment.[75] However, the patient’s decision to decline psychosocial treatment should not preclude or delay pharmacotherapy.[3]​​​ ​​

2nd line – acamprosate

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alcohol use disorder: pregnant
2nd line – 

acamprosate

There are no randomized controlled trials evaluating the effectiveness of pharmacologic interventions to reduce alcohol use or improve maternal, birth, and infant outcomes in pregnant women who consume alcohol or with alcohol use disorder.[114][115]​ 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, drug treatment may still be considered for women who are unable to stop drinking without pharmacologic support. 

Acamprosate is an option in pregnant women if the benefits outweigh the risks, but its efficacy is unclear.

Acamprosate normalizes 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. Pill burden may reduce its effectiveness. It is primarily metabolized 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 has been shown to increase the rate and duration of abstinence compared with placebo, though these studies have mostly excluded pregnant patients.[97][98]​​​​ Acamprosate is safe to use in patients who are actively drinking, but evidence for its use is from trials with people who have already stopped drinking. In meta-analysis (not specific to pregnant patients), the number needed to treat is 11 to prevent return to any drinking.[94]​ Diarrhea is also a common adverse effect.[94]​​ 

It is suggested that drugs are continued for at least 6 months due to the chronic, relapsing nature of the condition.[75]​ Further treatment is determined through shared decision-making.

Primary options

acamprosate: 666 mg orally three times daily

Consider – psychosocial treatment

Back
ONGOING
|
alcohol use disorder: pregnant
Consider – 

psychosocial treatment

Treatment recommended for SOME patients in selected patient group

​The use of pharmacologic treatment does not preclude other psychosocial support; and psychosocial support does not preclude the use of pharmacologic treatment. Indeed, the greatest efficacy may be seen in patients using a combination of pharmacotherapy and psychosocial treatment.[75]​​ ​​​However, the patient’s decision to decline psychosocial treatment should not preclude or delay pharmacotherapy.[3]

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