Association between proton pump inhibitor use and neurological or psychiatric disorders: a systematic review protocol

The objective of this review is to examine the association between proton pump inhibitors (PPIs) and neurological and/or psychiatric disorders in adults.

The association between PPIs and neurological and/or psychiatric disorders remains unclear, despite the widespread use of the medications. A systematic review is required to investigate the risk of developing neurological and/or psychiatric disorders following the use of PPIs.

Studies including participants aged ≥18 years and using any PPIs, including participants with comorbid conditions or using other medications, will be considered for inclusion. Randomized controlled trials, quasi-experimental studies, and observational studies examining the association of neurological and/or psychiatric disorders with the use of PPIs among adults will be included.

MEDLINE, Embase, PsycINFO, CINAHL, and Cochrane CENTRAL databases will be searched from inception until the present. Two authors will independently screen and review the titles, abstracts, and full texts. The methodological quality of included studies will be assessed using the JBI critical appraisal checklists. Study characteristics, populations, type and duration of PPI usage, status of existing neurological and/or psychiatric disorders, comorbidity conditions, use of other medications, identification of neurological and/or psychiatric disorders (International Classification of Diseases codes vs others), and estimation of the associated neurological and/or psychiatric disorders will be extracted. Studies will be pooled using statistical meta-analysis where available; otherwise, the findings will be presented in narrative format. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach for grading the certainty of evidence will be followed.

PROSPERO CRD42022355543.