Date of Award

January 2020

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Michael Bloch

Second Advisor

Andrés Martin

Abstract

Objective:

Aim 1: To examine the efficacy of antidepressant agents compared with placebo in reducing depressive symptoms in subjects with comorbid Alcohol Use Disorders (AUD).

Aim 2: To examine the efficacy of antidepressant agents compared with placebo on measures of alcohol consumption.

Data Sources:

Aim 1: PubMed was searched for randomized, placebo-controlled trials that examined the efficacy of antidepressant medications for treating depression symptoms with comorbid AUD.

Aim 2: Ovid MEDLINE (1946 to September 23, 2016) and CENTRAL (Issue 8, August 2016) were searched with no language limits for randomized placebo-controlled trials that examined the effects of antidepressant medications on alcohol consumption.

Study Selection:

Aim 1: Trials were included if they: 1) were randomized, placebo-controlled clinical trials, 2) examined the effects of an antidepressant medication for comorbid MDD and AUD, and 3) reported depression outcomes.

Aim 2: Trials were included if they: 1) were randomized, placebo-controlled clinical trials, 2) examined the effects of an antidepressant medication for comorbid MDD and AUD, and 3) reported alcohol consumption outcomes.

Data Extraction:

Aim 1: Random effects meta-analysis was utilized to examine standardized mean difference (SMD) in improvement of depressive symptoms and risk ratio for treatment response. Stratified subgroup analysis was used to examine the moderating effects of type of antidepressant medication and other trial characteristics.

Aim 2: We examined the effect of antidepressant treatment on four alcohol consumption outcomes: (1) drinking days, (2) drinks per day, (3) hazardous drinking days, and (4) abstinence rates. Our primary outcome was standardized mean difference for continuous measures and risk ratio for dichotomous outcomes using random effects meta-analysis. We also used stratified subgroup analysis to examine the moderating effects of type of antidepressant medication and diagnostic indication.

Results:

Aim 1: Eighteen distinct trial arms involving 1,318 participants were included in this systematic review and meta-analysis. In subjects with AUD, antidepressant medications significantly decreased depression severity compared with placebo (SMD=0.33±0.10 (95% Confidence Interval (CI): 0.14-0.51, k=18, z=3.4, p=0.001). Type of antidepressant medication did not significantly affect the magnitude of depressive symptom improvement compared with placebo (Test for subgroup differences χ2=2.15, df=2, p=0.34). TCAs (SMD=0.51±0.19 (95% CI: 0.15-0.88, k=3, z=2.7, p=0.006) and SSRIs (SMD=0.22±0.12 (95% CI: -0.01-0.46, k=10, z=1.9, p=0.06) suggested similar benefits for depressive symptoms in subjects with comorbid AUD. The use of concomitant psychotherapy (for either depression or alcohol use) (Test for subgroup differences χ2=9.9, df=1, p=0.002) or concomitant pharmacotherapy for AUD (Test for subgroup differences χ2=4.7, df=1, p=0.03) was associated with a significantly smaller measured treatment benefit of antidepressant agents.

Aim 2: Twenty-six trials involving 2,771 participants were included in this systematic review and meta-analysis. Overall, antidepressant use was not associated with significant changes in drinking outcomes (drinking days, drinks per day, abstinence rates, and hazardous drinking days). When antidepressants were utilized to treat comorbid depression symptoms, antidepressant treatment was associated with improved drinking outcomes on some (drinking days and drinks per day) but not all measures (abstinence rates and hazardous drinking days). When antidepressants were utilized primarily to treat symptoms of other disorders, antidepressant treatment was associated with worsened drinking outcomes on some (drinking days and drinks per day) but not all measures (abstinence rates and hazardous drinking days). Class of antidepressant treatment did not significantly affect any drinking-related outcomes.

Conclusion:

Aim 1: Our meta-analysis suggests that antidepressant medications significantly decrease depressive symptoms in participants with comorbid AUD. The magnitude of depressive symptom improvement in subjects with comorbid AUD appears similar to that achieved in MDD trials without comorbid substance use.

Aim 2: Antidepressant therapy results in improvement in some drinking outcomes when used for comorbid depression, though it may worsen these outcomes in the absence of comorbid depression. More research is needed on the impact of antidepressants on drinking outcomes, including the potential moderating effects of age, genotype, and depression and anxiety symptoms.

Comments

This is an Open Access Thesis.

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