Anxiety disorders and all-cause mortality: systematic review and meta-analysis

Purpose: The purpose of this study was to perform a systematic review and meta-analysis of prospective cohort studies that examined the relationship between anxiety disorders, or clinically significant anxiety symptoms, at baseline and all-cause mortality at follow-up relative to control participants without clinically significant anxiety. Methods: PubMed, EMBASE, PsycInfo, and CINAHL were searched through July 2015, along with manual searches of published reviews and forward and backward snowball searches of included studies. Studies were excluded if anxiety was not defined with a standardized instrument, or if participants were followed-up for 1 year or less. The initial search yielded 7901 articles after the removal of duplicates, of which 328 underwent full-text screening. Results: Forty-two estimates from 36 articles were included in the meta-analysis with a total sample of 127,552 participants and over 11,573 deaths. The overall hazard ratio (HR) estimate of mortality in clinically anxious participants relative to controls was 1.09 (95 % CI 1.01–1.16); however, this was reduced after adjusting for publication bias (1.03; 95 % CI 0.95–1.13). There was no evidence of increased mortality risk among anxious participants derived from community samples (0.99; 95 % CI 0.96–1.02) and in studies that adjusted for a diagnosis of depression (1.01; 95 % CI 0.96–1.06). Conclusions: These findings suggest that positive associations in the literature are attributable to studies in smaller samples, comorbid depression (or other psychiatric conditions) among participants, and possible confounding in medical patient samples followed-up for short durations.