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 We also searched for ongoing and unpublished studies via ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP)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: 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
antidepressants in 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 people with 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.