Impact of antidepressant use on the autonomic nervous system: A meta-analysis and systematic review

Changes in cardiac autonomic nervous system (ANS) regulation observed in psychiatric disorders may be mitigated by antidepressants. We meta-analyzed and systematically reviewed studies examining antidepressants' effects on ANS outcomes, including heart rate variability (HRV). We conducted a PRISMA/MOOSE-compliant search of PubMed and Scopus until March 28th, 2022. We included randomized placebo-controlled trials (RCTs) and pre-post studies, regardless of diagnosis. We pooled results in random-effects meta-analyses, pooling homogeneous study designs and outcomes. We conducted sensitivity analyses and assessed quality of included studies. Thirty studies could be meta-analyzed. Selective serotonin reuptake inhibitors (SSRIs) were significantly associated with a reduction in the square root of the mean-squared difference between successive R-R intervals (RMSSD) (SMD= -0.48) and skin conductance response (SMD= -0.55) in RCTs and with a significant increase in RMSSD in pre-post studies (SMD=0.27). In pre-post studies, tricyclic antidepressants (TCAs) were associated with a significant decrease in several HRV outcomes while agomelatine was associated with a significant increase in high frequency power (SMD= 0.14). In conclusion, SSRIs reduce skin conductance response but have no or inconclusive effects on other ANS outcomes, depending on study design. TCAs reduce markers of parasympathetic function while agomelatine might have the opposite effect. Studies are needed to investigate the impact of SSRIs on the recovery of cardiac ANS regulation after acute myocardial infarction, and the effects of newer antidepressants.