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

Depress Anxiety. 2019 Jan;36(1):63-71. doi: 10.1002/da.22843. Epub 2018 Oct 12.

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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antidepressive Agents / pharmacology*
  • Antidepressive Agents / therapeutic use*
  • Anxiety / complications*
  • Anxiety / drug therapy*
  • Anxiety / physiopathology
  • Biomarkers*
  • Citalopram / therapeutic use
  • Depression / diagnosis
  • Depression / drug therapy
  • Depression / physiopathology
  • Depression / psychology
  • Depressive Disorder, Major / complications
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / physiopathology
  • Depressive Disorder, Major / psychology*
  • Female
  • Heart Rate / drug effects*
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Sertraline / therapeutic use
  • Treatment Outcome
  • Venlafaxine Hydrochloride / administration & dosage
  • Venlafaxine Hydrochloride / therapeutic use
  • Young Adult

Substances

  • Antidepressive Agents
  • Biomarkers
  • Citalopram
  • Venlafaxine Hydrochloride
  • Sertraline

Associated data

  • ClinicalTrials.gov/NCT00693849