Mediators and Moderators in the Co-Occurring Anxiety and Alcohol Use Relationship: Protocol for a Systematic Review and Meta-Analysis
Authors: Guckel Tara , Prior Katrina , Newton Nicola Clare , Stapinski Lexine Ann 
Published: July 2023

Background
Anxiety and alcohol use commonly co-occur. Previous research has demonstrated the bidirectional and mutually reinforcing nature of this relationship, with an increasing body of research investigating the mediating and moderating mechanisms driving this association. Within the existing mediation and moderation research, however, there have been contrasting findings and, at times, null results among some population groups.

Objective
This protocol outlines a systematic review and meta-analysis aiming to synthesize and clarify mediators and moderators in the anxiety-alcohol and alcohol-anxiety relationships.

Methods
Systematic searches will be conducted in the electronic databases Medline, PsycINFO, Embase, Cochrane Central Register of Controlled Trials, Scopus, and Web of Science to identify studies that investigated mediators and moderators of the relationship between anxiety and alcohol use, including clinical and subclinical levels. Studies that look at the relationship between anxiety and alcohol use outcomes, as well as alcohol use and anxiety outcomes, will be included in order to capture an in-depth understanding of the mechanisms driving the association in either direction. No limits will be placed on study year or study language. Included study designs will be observational studies, including cohort, cross-sectional, and longitudinal studies, and secondary analyses of randomized controlled trials reporting quantitative results. Selected studies will also have their reference lists hand-searched for other relevant papers. Study quality will be assessed with the Joanna Briggs Institute Checklists for Analytical Cross-Sectional Studies and Cohort Studies. Mediators and moderators will be narratively synthesized in line with the biopsychosocial framework, where results will be grouped into biological, psychological, and social or environmental factors. If the data are sufficiently homogeneous, a meta-analysis will be conducted with mediation and moderation analyses synthesized separately. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework will also be used to assess the strength of cumulative evidence.

Results
Electronic database searches were conducted in September 2022. After duplicates were removed, a total of 7330 titles and abstracts were screened. Full-text reviewing is currently under way, with the results expected to be available by the end of 2023.

Conclusions
Given the significant individual and societal impacts of co-occurring anxiety and alcohol use, this review will help clarify mechanisms linking these two concerns. Identified mechanisms, where possible, can then be targeted in prevention, early intervention, and treatment approaches to improve the outcomes for individuals experiencing co-occurring anxiety and alcohol use.

Trial Registration
PROSPERO CRD42023358402; https://tinyurl.com/2m2e3enp

International Registered Report Identifier (IRRID)
DERR1-10.2196/48875