For
the first time doctors have shown that measuring changes in 24-hour heart rate
can reliably indicate whether or not someone is depressed. In practical terms,
this may give clinicians an objective "early warning" of potential
depression, as well as a rapid indication whether or not treatment is working,
so opening the way to more rapid and responsive treatment. Presenting results
of this pilot study at the ECNP virtual congress, lead researcher, Dr. Carmen
Schiweck (Goethe University, Frankfurt) said "Put simply, our pilot study
suggests that by just measuring your heart rate for 24 hours, we can tell with
90% accuracy if a person is currently depressed or not."
Scientists
have known that heart rate is linked to depression, but until now they have
been unable to understand exactly how one is related to the other. In part this
is because while heart rates can fluctuate quickly, depression both arrives and
leaves over a longer period, with most treatments taking months to take effect.
This makes it difficult to see whether or not changes in one's depressive state
might be related to heart
rate.
"Two
innovative elements in this study were the continuous registration of heart
rate for several days and nights, and the use of the new antidepressant
ketamine, which can lift depression more or less instantly. This allowed us to
see that average resting heart rate may change quite suddenly to reflect the
change in mood," said Schiweck.
Ketamine
has a history as both an anesthetic and a party drug (a drug of abuse). However
in December last year it was licensed to treat major depression
in Europe, after having been introduced in the USA a few months earlier.
Traditional antidepressants can take weeks to show an effect, in contrast
ketamine is rapid acting, with results often being seen in minutes.
As
Carmen Schiweck said "We knew that something was going on to link heart
rate to psychiatric disorders, but we didn't know what it was, and whether it
would have any clinical relevance. In the past researchers had shown that
depressed patients had consistently higher heart rates and lower heart rate
variability, but because of the time it takes to treat depression it had been
difficult to follow up and relate any improvement to heart rate. But when we
realized that ketamine leads to a rapid improvement in mood, we knew that we
might be able to use it to understand the link between depression and heart
rate."
Dr.
Schiweck performed this work in the Mind Body Research group at KU Leuven,
Belgium, with Dr. Stephan Claes as the principal investigator. The team worked
with a small sample of 16 patients
with Major Depressive Disorder, none of who had responded to normal treatment,
and 16 healthy controls. They measured their heartrates for 4 days and 3
nights, and then the volunteers with depression were given either ketamine
treatment or a placebo.
"We
found that those with depression had both a higher baseline heart rate, and a
lower heart rate variation, as we expected. On average we saw that depressed
patients had a heart rate which was roughly 10 to 15 beats per minutes higher
than in controls. After treatment, we again measured the heart rates and found
that both the rate and the heartrate fluctuation of the previously depressed
patients had changed to be closer to those found in the controls."
The
most striking finding was that the scientists were able to use 24-hour heart
rate as a 'biomarker' for depression. Heart rates were measured using a
wearable mini-ECG. The data was fed to an Artificial Intelligence program,
which was able to classify nearly all controls and patients correctly as being
depressed or healthy.
"Normally
heart rates are higher during the day and lower during the night.
Interestingly, it seems that the drop in heart rate during the night is
impaired in depression. This seems to be a way of identifying patients who are
at risk to develop depression or to relapse," said Schiweck.
The
team also found that patients with a higher resting heart rate responded better
to the treatment with Ketamine, which may help identify which patients are
likely to respond to which treatment.
Schiweck
noted, "We need to remember that this is a small proof-of-concept study: 6
of our of our 16 initial patients responded to treatment with at least a 30%
reduction on the Hamilton Rating scale for depression, so we need to repeat the
work with a larger, anti-depressant free sample. Our next step is to follow up
depressed patients and patients who are in remission, to confirm that the
changes we see can be used as an early warning system."
Commenting,
Professor Brenda Penninx of the Department of Psychiatry at Amsterdam
University Medical Centre, said, "This is an innovative proof-of-concept
study. My own group had previously studied short-term heart rate variability in
over a thousand depressed patients and controls, and we did not detect a
consistent differentiation, and found antidepressants to have more impact than
depression status itself. However, this study monitored heart rate variability
in the ambulatory setting for several days and nights, which gives unique night
and day information on the autonomic nervous system. It needs to be examined
whether these interesting findings hold in larger, more diverse treatment
settings."
Professor
Penninx was not involved in this work, this is an independent comment.
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