alcoholism

IMPORTANCE:

Alcohol consumption is associated with 88 000 US deaths annually. Although routine screening for heavy alcohol use can identify patients with alcohol use disorder (AUD) and has been recommended, only 1 in 6 US adults report ever having been asked by a health professional about their drinking behavior. Alcohol use disorder, a problematic pattern of alcohol use accompanied by clinically significant impairment or distress, is present in up to 14% of US adults during a 1-year period, although only about 8% of affected individuals are treated in an alcohol treatment facility.

OBSERVATIONS:

Four medications are approved by the US Food and Drug Administration to treat AUD: disulfiram, naltrexone (oral and long-acting injectable formulations), and acamprosate. However, patients with AUD most commonly receive counseling. Medications are prescribed to less than 9% of patients who are likely to benefit from them, given evidence that they exert clinically meaningful effects and their inclusion in clinical practice guidelines as first-line treatments for moderate to severe AUD. Naltrexone, which can be given once daily, reduces the likelihood of a return to any drinking by 5% and binge-drinking risk by 10%. Randomized clinical trials also show that some medications approved for other indications, including seizure disorder (eg, topiramate), are efficacious in treating AUD. Currently, there is not sufficient evidence to support the use of pharmacogenetics to personalize AUD treatments.

CONCLUSIONS AND RELEVANCE:

Alcohol consumption is associated with a high rate of morbidity and mortality, and heavy alcohol use is the major risk factor for AUD. Simple, valid screening methods can be used to identify patients with heavy alcohol use, who can then be evaluated for the presence of an AUD. Patients receiving a diagnosis of the disorder should be given brief counseling and prescribed a first-line medication (eg, naltrexone) or referred for a more intensive psychosocial intervention.

BACKGROUND:

Alcohol dependence is a major public health problem characterized by recidivism, and medical and psychosocial complications. The co-occurrence of major depression in people entering treatment for alcohol dependence is common, and represents a risk factor for morbidity and mortality, which negatively influences treatment outcomes.

OBJECTIVES:

To assess the benefits and risks of antidepressants for the treatment of people with co-occurring depression and alcohol dependence.

SEARCH METHODS:

We searched the Cochrane Drugs and Alcohol Group Specialised Register (via CRSLive), Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase from inception to July 2017. We also searched for ongoing and unpublished studies via ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (apps.who.int/trialsearch/).All searches included non-English language literature. We handsearched references of topic-related systematic reviews and the included studies.

SELECTION CRITERIA:

Randomized controlled trials and controlled clinical trials comparing antidepressants alone or in association with other drugs or psychosocial interventions (or both) versus placebo, no treatment, and other pharmacological or psychosocial interventions.

DATA COLLECTION AND ANALYSIS:

We used standard methodological procedures as expected by Cochrane.

MAIN RESULTS:

We included 33 studies in the review (2242 participants). Antidepressants were compared to placebo (22 studies), psychotherapy (two studies), other medications (four studies), or other antidepressants (five studies). The mean duration of the trials was 9.9 weeks (range 3 to 26 weeks). Eighteen studies took place in the USA, 12 in Europe, two in Turkey, and one in Australia. The antidepressant included in most of the trials was sertraline; other medications were amitriptyline, citalopram, desipramine, doxepin, escitalopram, fluoxetine, fluvoxamine, imipramine, mianserin, mirtazepine, nefazodone, paroxetine, tianeptine, venlafaxine, and viloxazine. Eighteen studies were conducted in an outpatient setting, nine in an inpatient setting, and six in both settings. Psychosocial treatment was provided in 18 studies. There was high heterogeneity in the selection of outcomes and the rating systems used for diagnosis and outcome assessment.Comparing antidepressants to placebo, low-quality evidence suggested that antidepressants reduced the severity of depression evaluated with interviewer-rated scales at the end of trial (14 studies, 1074 participants, standardized mean difference (SMD) -0.27, 95% confidence interval (CI) -0.49 to -0.04). However, the difference became non-significant after the exclusion of studies with a high risk of bias (SMD -0.17, 95% CI -0.39 to 0.04). In addition, very low-quality evidence supported the efficacy of antidepressants in increasing the response to the treatment(10 studies, 805 participants, risk ratio (RR) 1.40, 95% Cl 1.08 to 1.82). This result became non-significant after the exclusion of studies at high risk of bias (RR 1.27, 95% CI 0.96 to 1.68). There was no difference for other relevant outcomes such as the difference between baseline and final score, evaluated using interviewer-rated scales (5 studies, 447 participants, SMD 0.15, 95% CI -0.12 to 0.42).Moderate-quality evidence found that antidepressants increased the number of participants abstinent from alcohol during the trial (7 studies, 424 participants, RR 1.71, 95% Cl 1.22 to 2.39) and reduced the number of drinks per drinking days (7 studies, 451 participants, mean difference (MD) -1.13 drinks per drinking days, 95% Cl -1.79 to -0.46). After the exclusion of studies with high risk of bias, the number of abstinent remained higher (RR 1.69, 95% CI 1.18 to 2.43) and the number of drinks per drinking days lower (MD -1.21 number of drinks per drinking days, 95% CI -1.91 to -0.51) among participants who received antidepressants compared to those who received placebo. However, other outcomes such as the rate of abstinent days did not differ between antidepressants and placebo (9 studies, 821 participants, MD 1.34, 95% Cl -1.66 to 4.34; low-quality evidence).Low-quality evidence suggested no differences between antidepressants and placebo in the number of dropouts (17 studies, 1159 participants, RR 0.98, 95% Cl 0.79 to 1.22) and adverse events as withdrawal for medical reasons (10 studies, 947 participants, RR 1.15, 95% Cl 0.65 to 2.04).There were few studies comparing one antidepressant versus another antidepressant or antidepressants versus other interventions, and these had a small sample size and were heterogeneous in terms of the types of interventions that were compared, yielding results that were not informative.

AUTHORS' CONCLUSIONS:

We found low-quality evidence supporting the clinical use of antidepressantsin the treatment of people with co-occurring depression and alcohol dependence. Antidepressants had positive effects on certain relevant outcomes related to depression and alcohol use but not on other relevant outcomes. Moreover, most of these positive effects were no longer significant when studies with high risk of bias were excluded. Results were limited by the large number of studies showing high or unclear risk of bias and the low number of studies comparing one antidepressant to another or antidepressants to other medication. In people with co-occurring depression and alcohol dependence, the risk of developing adverse effects appeared to be minimal, especially for the newer classes of antidepressants (such as selective serotonin reuptake inhibitors). According to these results, in peoplewith co-occurring depression and alcohol dependence, antidepressants may be useful for the treatment of depression, alcohol dependence, or both, although the clinical relevance may be modest.