Depression Lowers HRV, and Antidepressants Act Differently
Depression comes with lower HRV before any drug is involved. Then the drugs part ways: sertraline flat, venlafaxine and mirtazapine down.
Evidence rating for the proposition “Antidepressant treatment lowers heart rate variability”: Uncertain
It depends on the drug, and depression lowers HRV before any drug is involved. A meta-analysis of 18 studies found lower HRV in depressed patients than in healthy controls. In a 118-patient randomized trial, six weeks of sertraline left HRV unchanged. In 41 patients on venlafaxine or mirtazapine, HRV total power declined over four weeks. In a 94-patient comparison, quetiapine was the medication linked to the lowest HRV. The meta-analysis found tricyclics decreased HRV, while SSRIs, mirtazapine and nefazodone had no significant impact.
Does depression itself lower HRV?
Yes, on average. A meta-analysis pooled 18 studies with 673 depressed participants and 407 healthy comparison participants, none with cardiovascular disease. Depressed participants had lower HRV. The gap widened with depression severity and was clearest in nonlinear HRV measures.
A randomized trial of 118 medication-free depressed patients saw the same. Before treatment, patients had lower HRV than age- and gender-matched healthy controls.
This matters for a wearable trend. A low starting number can predate any prescription. The wider link is covered in whether HRV reflects depression.
Does sertraline change HRV?
In the best-controlled test found here, no. The trial gave 118 medication-free patients either sertraline at 50 mg a day or placebo, alongside active or sham brain stimulation, for six weeks. HRV did not change with sertraline. It did not change with the stimulation either. HRV also did not rise in patients who responded clinically.
The meta-analysis pooled SSRIs, mirtazapine and nefazodone and found no significant impact on HRV despite patient response. Tricyclic medication decreased HRV. A cross-sectional comparison of 94 psychiatric patients also agrees on SSRIs. The 53 patients on sertraline or escitalopram did not stand out. The authors found the autonomic effects of antidepressants not significant in that sample.
The trial's authors discuss whether low HRV is a trait marker of depression. On that reading, it persists after treatment works.
2 studies
- In 118 medication-free depressed patients randomized to sertraline 50 mg a day or placebo (with active or sham brain stimulation) for six weeks, HRV did not change with either treatment, nor with clinical response. Patients had lower HRV than healthy controls at the start.
- In 18 studies covering 673 depressed and 407 healthy participants, depression was associated with lower HRV. Tricyclic medication decreased HRV. SSRIs, mirtazapine and nefazodone had no significant impact. A variety of antidepressant treatments did not resolve the reduction despite resolution of symptoms.
What about venlafaxine, mirtazapine and quetiapine?
These are the drugs where HRV fell. A trial studied 28 non-depressed controls and 41 moderately depressed patients. Twenty patients took venlafaxine and 21 took mirtazapine. HRV was measured after a six-day washout, then at 14 and 28 days of treatment.
HRV total power declined during treatment. Medication type and remission status at four weeks were not related to the size of the change. The authors concluded that both drugs led to a further decline.
The abstract describes no placebo arm. Without one, the drug cannot be separated from time or from the illness. The meta-analysis reached a different verdict on mirtazapine, which it found had no significant impact. The two sources disagree.
Quetiapine stood out in the 94-patient comparison. The augmentation group, an antidepressant plus quetiapine, had the lowest total power, very low frequency power and low frequency power. Age and quetiapine use both correlated negatively with those measures. The authors conclude that quetiapine causes an overt decrease in HRV.
2 studies
- In 41 depressed patients (20 on venlafaxine, 21 on mirtazapine) and 28 controls, HRV total power declined over 14 and 28 days of treatment. Medication type and remission after four weeks were unrelated to the change.
- In 94 patients grouped as no antidepressant (19), SSRI (53), venlafaxine or mirtazapine (9) or antidepressant plus quetiapine (13), the augmentation group had the lowest total, very low frequency and low frequency power.
What about tricyclics and paroxetine?
Tricyclics are the class with the clearest decline. The 18-study meta-analysis found that tricyclic medication decreased HRV. A separate meta-analysis of paroxetine, an SSRI, included five studies. It found no significant change in SDNN. It found higher low frequency and high frequency indices. The authors rate the evidence as low to very low quality and call for confirmation. That points the opposite way from a simple SSRI-lowers-HRV story.
One point recurs. The 18-study meta-analysis concluded that antidepressant treatments do not resolve the HRV reduction even when symptoms resolve. HRV and mood do not necessarily move together.
What do these studies not settle?
None of the studies explains a mechanism. The abstracts describe patterns in HRV, not why venlafaxine and mirtazapine tracked with decline while sertraline did not.
Sample sizes were modest and split across several subgroups. Only the sertraline trial describes a placebo arm. All participants had depression, anxiety or related symptoms. Nothing here says what an antidepressant does to HRV in someone without a mood disorder.
The trials measured HRV in clinics. Follow-up ran six weeks or less. Whether an early change persists, reverses or settles at six months or longer is not covered. A single reading is also hard to read on its own, as what counts as a good HRV varies widely between people.
None of these studies used a consumer wearable. Terhardt et al. measured supine and upright HRV in a clinic after a washout. Brunoni et al. followed patients for six weeks. Huang et al. compared psychiatric patients at a single point. Whether a nightly wrist reading would show the same pattern is not known, and none followed patients beyond a few weeks.
Common questions
Do antidepressants lower HRV?
It depends on the drug. In a 118-patient randomized trial, six weeks of sertraline left HRV unchanged. In 41 patients on venlafaxine or mirtazapine, HRV total power declined over four weeks, though that study had no placebo arm.
Is low HRV caused by depression or by the medication?
Depression alone goes with lower HRV. A meta-analysis of 18 studies found lower HRV in depressed patients than in healthy controls, and a trial found it in medication-free patients before treatment.
Does HRV recover when depression improves?
Not reliably. The 18-study meta-analysis concluded that antidepressant treatments do not resolve the HRV reduction despite symptom resolution. In the sertraline trial, HRV did not rise with clinical response.
Does quetiapine affect HRV?
In a 94-patient comparison, the group taking an antidepressant plus quetiapine had the lowest HRV, and quetiapine use correlated negatively with several HRV measures. The authors conclude that quetiapine causes an overt decrease.
Do SSRIs lower HRV?
Not in the studies reviewed here. Sertraline did not change HRV in a randomized trial, and patients on sertraline or escitalopram did not stand out in a 94-patient comparison. A paroxetine meta-analysis found higher low and high frequency indices but no SDNN change, on low-quality evidence.
Sources
- Heart rate variability is a trait marker of major depressive disorder: evidence from the sertraline vs. electric current therapy to treat depression clinical study.
- Impact of depression and antidepressant treatment on heart rate variability: a review and meta-analysis.
- Heart rate variability during antidepressant treatment with venlafaxine and mirtazapine.
- The Effects of Antidepressants and Quetiapine on Heart Rate Variability.
- The effect of paroxetine on heart rate variability in patients with major depressive disorder: A systematic review and meta-analysis.