Heart rate variability as a biomarker of anxious depression response to antidepressant medication

Abstract

Background: There is a need to identify biomarkers of treatment outcomes for major depressive disorder (MDD) that can be disseminated. We investigated the predictive utility of pretreatment heart rate variability (HRV) for outcomes of antidepressant medication in MDD, with pretreatment anxious depression as a hypothesized moderator of HRV effects.

Methods: A large, randomized, multicenter practical trial (International Study to Predict Optimized Treatment in Depression) in patients with current nonpsychotic MDD (N = 1,008; 722 completers) had three arms: escitalopram, sertraline, and venlafaxine-extended release. At pretreatment, patients were defined as having anxious (N = 309) versus nonanxious (N = 413) depression and their resting high-frequency HRV (root mean square of successive differences) was assessed. Patients' usual treating clinicians managed medication. At 8 weeks, primary outcomes were clinician-rated depressive symptom response and remission; secondary outcomes were self-reported response and remission.

Results: Pretreatment HRV predicted antidepressant outcomes as a function of anxious versus nonanxious depression. In anxious depression, patients with higher HRV had better outcomes, whereas patients with lower HRV had poorer outcomes. In nonanxious depression, patients with lower HRV had better outcomes, whereas patients with higher HRV had poorer outcomes. Some simple effects were not significant. Results did not differ by treatment arm and remained significant when controlling for important covariates.

Conclusions: These findings inform a precision medicine approach in which clinical and biological assessments may be integrated to facilitate treatment outcome prediction. Knowing about HRV may help determine which patients with anxious depression could benefit from antidepressants and which patients may require a different treatment approach.

Trial registration: ClinicalTrials.gov NCT00693849.

Keywords: antidepressant; anxious depression; depression; heart rate variability; outcome; treatment.

© 2018 Wiley Periodicals, Inc.

Figures

Figure 1.

Plots of the predicted probabilities of response/remission as a function of pre-treatment high-frequency heart rate variability (root mean square of differences of successive RR intervals; RMSSD) and anxious versus nonanxious depression. Clinician-reported response and remission on the HRSD17 defined as ≥50% reduction in total score from weeks 0 to 8 and total score≤7 at week 8, respectively. Self-reported response and remission on the QIDS-SR16 defined as ≥50% reduction in total score from weeks 0 to 8 and total score≤5 at week 8, respectively. Results are adjusted for all other covariates in the models. Range of RMSSD represents mean ±2 standard deviations. Values below −0.68 and above 0.68 each represent approximately 16% of patients. Error bars denote ± standard error.

Figure 2.

Plots of the predicted probabilities of response/remission as a function of pre-treatment heart rate (HR) and anxious versus nonanxious depression. Clinician-reported response and remission on the HRSD17 defined as ≥50% reduction in total score from weeks 0 to 8 and total score≤7 at week 8, respectively. Self-reported response and remission on the QIDS-SR16 defined as ≥50% reduction in total score from weeks 0 to 8 and total score≤5 at week 8, respectively. Results are adjusted for all other covariates in the models. Range of HR represents mean ±2 standard deviations. Values below −10.7 and above 10.7 each represent approximately 16% of patients. Error bars denote ± standard error.