Clinical Interventions For Adults With Comorbid Alcohol Use And Depressive Disorders: A Systematic Review And Network Meta-Analysis

Author summary Why was this study done?Alcohol use disorders (AUDs) and depressive disorders are prevalent behavioral health conditions among adult populations, often co-occur, and have significant personal, societal, and economic consequences.

Existing systematic reviews and clinical practice guidelines often on either AUDs or depressive disorders, despite the prevalence and significance of their co-occurrence.

The objective of this review is to examine the available evidence on the effectiveness of clinical interventions for adult patients with co-occurring AUD and depressive disorders.

What did the researchers do and find?We conducted a systematic review and network meta-analysis (NMA) of 36 randomized controlled trials (RCTs) with 2,729 participants evaluating 14 pharmacological and 4 psychological interventions for adults with co-occurring AUDs and depressive disorders.

We have very low confidence in all estimates of intervention effects on our primary outcomes (i.e., remission from depression and remission from alcohol use).

We found that cognitive behavioral therapies (CBTs) likely reduced, and tricyclic antidepressants (TCAs) may have resulted in a slight reduction of depressive symptoms, selective serotonin reuptake inhibitors (SSRIs) likely increased functional status, SSRIs and CBTs may have resulted in a slight reduction of alcohol use, and SSRIs also likely resulted in an increased risk of experiencing an adverse event.

We have very low confidence in all other effect estimates, and we did not have high confidence in any effect estimates.

What do these findings mean?We did not have high confidence in any effect estimates, and we have very low confidence in the vast majority of estimates of intervention effects across all outcomes.

For policy and practice, we are very uncertain about the existence (or not) of any non-null effects for our primary outcomes of remission from depression and remission from alcohol use. The available evidence does suggest potentially actionable benefits at postintervention of CBTs for depressive symptoms and alcohol use, TCAs for depressive symptoms, and SSRIs for alcohol use and functional status-although SSRIs also likely have higher risks of adverse events (including serious adverse events).

For research, future trials are needed that are prospectively registered, adequately powered, fit for pragmatic purposes, comprehensively report study information and outcomes, and evaluate interventions discussed in clinical practice guidelines yet missing from the current body of evidence.

BackgroundUncertainty remains regarding the effectiveness of treatments for patients diagnosed with both an alcohol use disorder (AUD) and depressive disorder. This study aimed to compare the effectiveness of clinical interventions for improving symptoms of adults with co-occurring AUDs and depressive disorders.

Methods and findingsWe searched CINAHL, ClinicalTrials.gov, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Excerpta Medica Database, International Clinical Trials Registry Platform (ICTRP), PubMed, PsycINFO, and Web of Science from inception to December 2020. We included randomized controlled trials (RCTs) evaluating clinical interventions for adults with co-occurring AUDs and depressive disorders. Two independent reviewers extracted study-level information and outcome data. We assessed risk of bias using the Cochrane Risk of Bias tool, used frequentist random effects models for network meta-analyses, and rated our confidence in effect estimates using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Primary outcomes were remission from depression and alcohol use. Secondary outcomes were depressive symptoms, alcohol use, heavy drinking, health-related quality of life, functional status, and adverse events. We used standardized mean differences (SMDs) for continuous outcomes and odds ratios (ORs) for dichotomous outcomes to estimate intervention effects. Overall, 36 RCTs with 2,729 participants evaluated 14 pharmacological and 4 psychological interventions adjunctive to treatment as usual (TAU). Studies were published from 1971 to 2019, conducted in 13 countries, and had a median sample size of 50 participants (range: 14 to 350 participants). We have very low confidence in all estimates of intervention effects on our primary outcomes (i.e., remission from depression and remission from alcohol use). We have moderate confidence that cognitive behavioral therapies (CBTs) demonstrated greater benefit than no additional treatment (SMD = -0.84; 95% confidence interval [CI], -1.05 to -0.63; p < 0.001) for depressive symptoms and low confidence (SMD = -0.25; 95% CI, -0.47 to -0.04; p = 0.021) for alcohol use. We have low confidence that tricyclic antidepressants (TCAs) demonstrated greater benefit than placebo (SMD = -0.37; 95% CI, -0.72 to -0.02, p = 0.038) for depressive symptoms. Compared with placebo, we have moderate confidence that selective serotonin reuptake inhibitors (SSRIs) demonstrated greater benefit for functional status (SMD = -0.92; 95% CI, -1.36 to -0.47, p < 0.001) and low confidence for alcohol use (SMD = -0.30; 95% CI, -0.59 to -0.02, p = 0.039). However, we have moderate confidence that patients receiving SSRIs also were more likely to experience an adverse event (OR = 2.20; 95% CI, 0.94 to 5.16, p = 0.07). We have very low confidence in all other effect estimates, and we did not have high confidence in any effect estimates. Limitations include the sparsity of evidence on intervention effects over the long term, risks of attrition bias, and heterogeneous definitions of adverse events in the evidence base.

ConclusionsWe are very uncertain about the existence (or not) of any non-null effects for our primary outcomes of remission from depression and remission from alcohol use. The available evidence does suggest that CBTs likely reduced, and TCAs may have resulted in a slight reduction of depressive symptoms.SSRIs likely increased functional status, and SSRIs and CBTs may have resulted in a slight reduction of alcohol use. However, patients receiving SSRIs also likely had an increased risk of experiencing an adverse event. In addition, these conclusions only apply to postintervention and are not against active comparators, limiting the understanding of the efficacy of interventions in the long term as well as the comparative effectiveness of active treatments. As we did not have high confidence in any outcomes, additional studies are warranted to provide more conclusive evidence.