Real-World Effectiveness of Pharmacotherapy for Alcohol Use Disorder

man holding a glass of alcohol
man holding a glass of alcohol
This study aimed to study the effectiveness of approved pharmacologic treatments (disulfiram, acamprosate, naltrexone, nalmefene) for alcohol-related disorder.

Study data published in Addiction describe the relative efficacies of various pharmacologic treatments for alcohol use disorder (AUD). In a longitudinal cohort study conducted in Sweden, naltrexone monotherapy and naltrexone combined with disulfiram or acamprosate were associated with lower risk for hospitalization due to alcohol-related causes. By contrast, benzodiazepine use was associated with increased risk of AUD-associated hospitalization and increased risk of all-cause mortality.

Although psychotherapy is the primary treatment modality for AUD, pharmaceutical intervention may also improve outcomes. To assess the effectiveness of available pharmacologic treatments for AUD, investigators conducted a population-based cohort study of patients with AUD.

Data were extracted prospectively from nationwide Swedish registers, including the National Patient Register and the Prescribed Drug Register. All residents of Sweden aged 16 to 64 years at the time of AUD diagnosis with first-time AUD treatment registered between 2006 and 2016 were eligible for inclusion.

The main outcome was hospitalization due to AUD-related causes. Cox regression models were used to assess the relationship between AUD treatment regimens and subsequent risk for AUD-related hospitalization. Models were adjusted for age, sex, education level, number of prior AUD-related hospitalizations, medical comorbidities, and use of psychotropic drugs.

The total cohort comprised 125,556 patients, among whom 78,434 (62.5%) were men. Mean age at AUD diagnosis was 38.1 plus or minus 15.9 years. Median follow-up time was 4.6 years.

A total of 32,129 (25.6%) patients used any drug for the treatment of AUD, including disulfiram (n=19,274; 15.4%), acamprosate (n=11,432; 9.1%), naltrexone (n=10,872; 8.7%), and nalmefene (n=693; 0.6%). Additionally, 6398 patients (5.1%) used 2 or more medications concurrently.

Overall, 30,044 patients (23.9%) experienced hospitalization during follow-up. In regression models, naltrexone combined with acamprosate (hazard ratio [HR], 0.74; 95% CI, 0.61-0.89), naltrexone combined with disulfiram (HR, 0.76; 95% CI, 0.60-0.96), and naltrexone monotherapy (HR, 0.89; 95% CI, 0.81-0.97) were each associated with lower risk for AUD-related hospitalization compared with other medication regimens. This association persisted among patients with more severe AUD.

During follow-up, 3173 patients (2.5%) were hospitalized due to alcohol-related somatic causes. Polytherapy of any kind was associated with reduced risk for this type of hospitalization (HR, 0.31; 95% CI, 0.12-0.83) compared with no drug use.

Disulfiram monotherapy was also associated with reduced risk of hospitalization due to alcohol-related somatic causes (HR, 0.61; 95% CI, 0.42-0.89).

A total of 42,678 (34.0%) patients used benzodiazepines or related drugs during follow-up. Benzodiazepine use was associated with significantly increased risk for hospitalization (HR, 1.18; 95% CI, 1.14-1.22; P <.0001) compared with no benzodiazepine use. Benzodiazepines and related drugs were also associated with increased risk of all-cause mortality during follow-up (HR, 1.11; 95% CI, 1.04-1.19; P =.0034).

In this large-scale cohort study, AUD treatment with naltrexone monotherapy or naltrexone in combination with other medications was associated with decreased risk for AUD-related hospitalization. Acamprosate monotherapy did not have any observed beneficial effect on hospitalization rates, while benzodiazepines and related drugs appeared to increase the risk of poor outcomes.

Regarding study limitations, investigators noted that data about alcohol consumption patterns were not available. As such, the direct effect of medications on alcohol use could not be observed.

Further study is needed to confirm the effects of pharmaceutical intervention on AUD-related outcomes.  

“According to the data presented here, naltrexone and drug-combinations in particular seem to be effective in the treatment of AUD and are recommended to be used as part of treatment protocol; the use of benzodiazepines should be avoided,” the investigators wrote.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Heikkinen M, Taipale H, Tanskanen A, Mittendorfer-Rutz E, Lähteenvuo M, Tiihonen J. Real-world effectiveness of pharmacological treatments of alcohol use disorders in a Swedish nation-wide cohort of 125 556 patients. Published online January 4, 2021. Addiction. doi:10.1111/add.15384