Autonomic nervous system dysfunction in psychiatric disorders and the impact of psychotropic medications: a systematic review and meta-analysis

Abstract

Background: Autonomic nervous system (ANS) dysfunction is a putative underlying mechanism for increased cardiovascular disease risk in individuals with psychiatric disorders. Previous studies suggest that this risk may be related to psychotropic medication use. In the present study we systematically reviewed and analyzed published studies of heart rate variability (HRV), measuring ANS output, to determine the effect of psychiatric illness and medication use.

Methods: We searched for studies comparing HRV in physically healthy adults with a diagnosed psychiatric disorder to controls and comparing HRV pre- and post-treatment with a psychotropic medication.

Results: In total, 140 case-control (mood, anxiety, psychosis, dependent disorders, k = 151) and 30 treatment (antidepressants, antipsychotics; k = 43) studies were included. We found that HRV was reduced in all patient groups compared to controls (Hedges g = -0.583) with a large effect for psychotic disorders (Hedges g = -0.948). Effect sizes remained highly significant for medication-free patients compared to controls across all disorders. Smaller and significant reductions in HRV were observed for specific antidepressants and antipsychotics.

Limitations: Study quality significantly moderated effect sizes in case-control analyses, underscoring the importance of assessing methodological quality when interpreting HRV findings.

Conclusion: Combined findings confirm substantial reductions in HRV across psychiatric disorders, and these effects remained significant even in medication-free individuals. Reductions in HRV may therefore represent a significant mechanism contributing to elevated cardiovascular risk in individuals with psychiatric disorders. The negative impact of specific medications on HRV suggest increased risk for cardiovascular disease in these groups, highlighting a need for treatment providers to consider modifiable cardiovascular risk factors to attenuate this risk.

Figures

Fig. 1

Summary effect estimates comparing significant reductions in heart rate variability (HRV) in psychiatric disorder subgroups compared to healthy controls. Open diamonds depict summary effect sizes of each subgroup; filled diamond reflects the overall summary effect across groups. Diamond width indicates the 95% confidence interval (CI) for each summary effect size.

Fig. 2

Results of meta-regression analyses in case–control studies examining effects of continuous moderators on the effect sizes of (A) mean patient age, (B) the proportion of men in the patient group, (C) independent study quality ratings and (D) year of publication. Studies are indicated by open circles, with size indicating relative weight.

Fig. 3

Effects of antidepressant use on heart rate variability (HRV) in individuals with a mood or anxiety disorder. Removal of the outlier in the tricyclic antidepressant (TCA) group shifted the effect size of the TCA subgroup (Hedges g = −0.666, 95% confidence interval [CI] −0.900 to −0.432, p < 0.001) and the overall effect size (Hedges g = −0.231, 95% CI −0.364 to −0.097, p = 0.001). Point estimates are depicted by filled circles, with sizes indicating the relative weight of each study’s effect size estimate to the analysis. Open diamonds depict summary effects sizes of each subgroup; the filled diamond reflects the overall summary effect across groups. Line and diamond width indicate 95% CIs. SNRI = serotonin-norepinephrine reuptake inhibitor antidepressant; SSRI = selective serotonin reuptake inhibitor antidepressant.

Fig. 4

Effects of antipsychotic use on heart rate variability (HRV) in individuals with schizophrenia. Point estimates are depicted by closed circles, with size indicating the relative weight of each study’s effect size estimate to the analysis. Open diamonds depict summary effect sizes of each subgroup; filled diamond reflects the overall summary effect across groups. Line and diamond width indicate 95% confidence intervals (CIs).