Key messages
• Compared to psychosocial interventions alone, adding medications is probably safe and helpful for people with alcohol use disorder (AUD) in reducing alcohol use.
• Due to the limited number of available studies, we do not know if combined psychosocial interventions and medications, when compared to medications alone or no treatment or usual care, is helpful for people with AUD.
• More studies are needed looking at the effects of combined interventions compared to medications alone or no treatment or usual care.
What is alcohol use disorder (AUD)?
AUD is a mental disorder where there is an inability to control alcohol consumption and frequent episodes of uncontrolled alcohol use, related to an increased risk of car accidents, premature death, and diseases like cancer, liver cirrhosis, and neurological disorders.
How is AUD treated?
Psychosocial interventions and medications are used to help people with AUD to reduce alcohol consumption. Psychosocial interventions commonly used in the treatment of people with AUD are:
• cognitive behavioural interventions (aimed at helping people to recognise and modify their negative thoughts and beliefs, and unwanted behaviours, through behavioural tasks and skills to deal with the desire to consume alcohol);
• contingency management interventions (aimed at rewarding people who reduce alcohol use through money, vouchers, or prizes);
• motivational interviewing (aimed at increasing motivation to reduce alcohol use);
• twelve-step facilitation (interventions that have adapted the methods of Alcoholics Anonymous and encouraged Alcoholics Anonymous attendance).
Of the available medications, the following have been approved by the main regulatory agencies:
• acamprosate (recommended to maintain abstinence);
• disulfiram (recommended to maintain abstinence);
• naltrexone (recommended to both achieve and maintain abstinence and reduce alcohol consumption).
What did we want to find out?
We wanted to find out whether combined medications and psychosocial interventions is more effective than psychosocial interventions alone, medications alone, or usual care (education or information about alcohol use) in helping people with AUD to reduce or stop alcohol use.
What did we do?
We searched for studies where people were assigned randomly to one of two or more treatment groups that compared the combination (medications plus psychosocial interventions) with psychosocial intervention alone, medication alone, or usual care. We summarised the results of the studies and rated our confidence in the evidence based on factors such as study methods and sizes.
What did we find?
We found 21 studies with 4746 people with AUD who were treated as outpatients for approximately 4 months.
Participants were mostly men, aged about 44 years, who reported drinking approximately 12 drinks per drinking day, with approximately 70% of drinking days. The studies were conducted in the USA, Europe, and Canada. Most studies received public funds.
We found 20 studies (4498 participants) comparing combined pharmacological and psychosocial interventions to a psychosocial intervention alone. We found only a limited number of studies and participants that compared the combined treatment to medication alone (3 studies; 1871 participants) or treatment as usual (2 studies; 1623 participants). In most cases, the combined treatment consisted of cognitive behavioural therapy as the psychosocial intervention and naltrexone as the medication.
Compared to psychosocial interventions alone, combined treatment probably reduces the number of people who report heavy drinking and may increase the number of people who maintain continuous abstinence. The combined treatment probably has little to no effect on the rate of abstinent days, the risk of serious unwanted effects (i.e. death or events requiring hospitalisation), and the number of people who fail to complete treatment. It may have little to no effect on the rate of days in which people consume heavy amounts of alcohol, the number of drinks per drinking day, and the risk of unwanted effects.
We are uncertain whether combined treatment, when compared to medications alone, reduces the number of drinks per drinking day. It may have little to no effect on the rate of abstinent days and on the number of people who do not complete the treatment for any reason. We are uncertain about the effect on the number of people who maintain continuous abstinence, those who consume heavy amounts of alcohol, and those who do not complete treatment due to unwanted effects.
We are uncertain about the effect of combined treatment, when compared to treatment as usual, on the number of people who consume heavy amounts of alcohol, who do not complete the treatment, and on the rate of abstinent days.
Limitations of the evidence
Our results may not apply to the various types of people with AUD, all psychosocial and pharmacological interventions, and countries, since the studies did not look at every available treatment for AUD, and they were mainly carried out in the USA and Europe.
How up-to-date is this evidence?
The evidence is current to November 2023.
As implications for practice, our findings indicate that adding pharmacological to psychosocial interventions is safe and helps people with AUD recover. These conclusions are based on low- to moderate-certainty evidence.
Given the few studies and very low-certainty evidence, any benefits of adding psychosocial to pharmacological interventions or comparing the combined intervention to TAU are less clear. As implications for research, further studies should investigate the effects of the combined intervention compared to pharmacotherapy or TAU.
Alcohol use disorder (AUD) is a mental disorder characterised by a strong desire to consume alcohol and impaired control of alcohol use, with devastating consequences. Many people with AUD do not respond to psychosocial or pharmacological interventions when these are provided alone. Combining these interventions may improve the response to treatment, though evidence remains limited.
To assess the effects of combined pharmacological and psychosocial interventions for the treatment of AUD in adults.
We searched CENTRAL, MEDLINE, Embase, three other databases, and two trials registers in November 2023, without language restrictions.
We included randomised controlled trials (RCTs) comparing combined pharmacological and psychosocial interventions versus pharmacological or psychosocial interventions alone, or no intervention/treatment as usual (TAU), in adults with AUD.
Our primary outcomes were continuous abstinent participants, frequency of use (measured as heavy drinkers, percentages of abstinent days, heavy-drinking days), amount of use (number of drinks per drinking day), adverse events, serious adverse events, dropouts from treatment, and dropouts due to adverse events.
We assessed risk of bias using Cochrane's RoB 1 tool, performed random-effects meta-analyses, and evaluated the certainty of evidence according to the GRADE approach.
We included 21 RCTs (4746 participants). The most studied pharmacological and psychosocial interventions were naltrexone (81.0%) and cognitive behavioural therapy (66.7%), respectively. Most participants were men (74%), aged about 44 years, with AUD, without comorbid mental disorders or other substance use disorders; 15 RCTs detoxified participants before treatment.
We judged 28.5% of the studies as at low risk of bias for random sequence generation, allocation concealment, performance bias for objective and subjective outcomes, and detection bias for subjective outcomes; all studies were at low risk of detection bias for objective outcomes; 85.7% of studies were at low risk of attrition bias; 14.2% of studies were at low risk of reporting bias.
1) Compared to psychosocial intervention alone, combined pharmacological and psychosocial interventions probably reduce the number of heavy drinkers (above the clinically meaningful threshold (MID) of 2%; absolute difference (AD) −10%, 95% confidence interval (CI) −18% to −2%; risk ratio (RR) 0.86, 95% CI 0.76 to 0.97; 8 studies, 1609 participants; moderate-certainty evidence).
They may increase continuous abstinent participants (MID 5%; AD 5%, 95% CI 1% to 11%; RR 1.17, 95% CI 1.02 to 1.34; 6 studies, 1184 participants; low-certainty evidence).
They probably have little to no effect on:
• the rate of abstinent days (MID 8%; mean difference (MD) 4.16, 95% CI 1.24 to 7.08; 10 studies, 2227 participants);
• serious adverse events (MID 1%; AD −2%, 95% CI −3% to 0%; RR 0.20, 95% CI 0.03 to 1.12; 4 studies; 524 participants);
• dropouts from treatment (MID 10%; AD −3%, 95% CI −5% to 0%; RR 0.89, 95% CI 0.79 to 1.01; 15 studies, 3021 participants); and
• dropouts due to adverse events (MID 5%; AD 2%, 95% CI 0% to 5%; RR 1.91, 95% CI 1.04 to 3.52; 8 studies, 1572 participants) (all moderate-certainty evidence).
They may have little to no effect on:
• heavy-drinking days (MID 5%; MD −3.49, 95% CI −8.68 to 1.70; 4 studies, 470 participants);
• number of drinks per drinking day (MID 1 drink; MD −0.57, 95% CI −1.16 to 0.01; 7 studies, 805 participants); and
• adverse events (MID 30%; AD 17%, 95% CI −5% to 46%; RR 1.25, 95% CI 0.93 to 1.68; 4 studies, 508 participants) (all low-certainty evidence).
2) Compared to pharmacological intervention alone, combined pharmacological and psychosocial interventions may have little to no effect on:
• the rate of abstinent days (MID 8%; MD −1.18, 95% CI −4.42 to 2.07; 2 studies, 1158 participants); and
• dropouts from treatment (MID 10%; AD 1%, 95% CI −10 to 14%; RR 0.98, 95% CI 0.65 to 1.47; 3 studies, 1246 participants) (all low-certainty evidence).
We are uncertain about their effect on:
• continuous abstinent participants (MID 5%; AD 3%, 95% CI −5% to 18%; RR 1.22, 95% CI 0.62 to 2.40; 1 study, 241 participants);
• the number of heavy drinkers (MID 2%; AD 2%, 95% CI −4% to 8%; RR 1.03, 95% CI 0.94 to 1.12; 1 study, 917 participants);
• the number of drinks per drinking day (MID 1 drink; MD −2.40, 95% CI −3.98 to −0.82; 1 study, 241 participants); and
• dropouts due to adverse events (MID 5%; AD −1%, 95% CI −3% to 6%; RR 0.61, 95% CI 0.14 to 2.72; 2 studies, 1165 participants) (all very low-certainty evidence).
3) We are uncertain about the effect of combined pharmacological and psychosocial interventions, when compared to TAU, on:
• the number of heavy drinkers (MID 2%; AD −5%, 95% CI −13% to 2%; RR 0.93, 95% CI 0.83 to 1.03; 1 study, 616 participants);
• the rate of abstinent days (MID 8%; MD 3.43, 95% CI −1.32 to 8.18; 1 study, 616 participants);
• dropouts from treatment (MID 10%; AD 0%, 95% CI −10% to 15%; RR 0.98, 95% CI 0.58 to 1.65; 2 studies, 696 participants); and
• dropouts due to adverse events (MID 5%; AD 3%, 95% CI 0% to 15%; RR 2.97, 95% CI 0.70 to 12.67; 1 study, 616 participants) (all very low-certainty evidence).
The certainty of evidence ranged from moderate to very low, downgraded mainly due to risk of bias and imprecision.