Predictive value of heart rate in treatment of major depression with ketamine in two controlled trials

Meyer, Torsten; Brunovský, Martin; Horáček, Jiří; Novák, Tomáš; Andrashko, Veronika; Seifritz, Erich; Olbrich, Sebastian

doi:10.1016/j.clinph.2021.01.030

Cited by 13 publications

(17 citation statements)

References 38 publications

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“…We also find robust differences between between ketamine and saline conditions: (1) physiological measures: increased PR, decreased PRV, increased absolute HbO and decreased HbR, and elevated EDA (measured by an external sensor) during ketamine dosing, and (2) neural measures: decrease in fALFF and in the global brain functional connectivity of the prefrontal cortex following ketamine administration. These results are generally consistent with findings reported by previous studies (apart from the global functional connectivity result) 45,50,63,64 .…”

Section: Discussionsupporting

confidence: 93%

“…We found a significant increase in PR during the ketamine dosing session (82%) compared to the saline session as well as a significant decrease in PRV (91%) (Fig. 2d)-both findings were confirmed with the external PPG sensor as well and are consistent with those described in prior literature 45 .…”

Section: Ketamine Induces Altered States Of Consciousness and Reduces...supporting

confidence: 91%

“…Although ketamine is thought to preserve baseline respiratory parameters 44 , it is sympathomimetic and has known effects on cardiac signals such as heart rate (HR) and heart rate variability (HRV) 45 . In fact, cardiac measures alone have been suggested as potential biomarkers of treatment outcomes in patients with major depressive disorder (MDD) 45,46 . Consequently, we tested our ability to retrieve several physiological variables from our data and further demonstrate the effects of the active drug as compared to the placebo control.…”

Section: Resultsmentioning

confidence: 99%

“…Ketamine affects the cardiovascular system, absolute cerebrovascular hemoglobin oxygenation and concentration but preserves respiratory parameters Often regarded as artifacts, fNIRS data are rich in physiological information from which multiple physiological features can be extracted 42,43 . Although ketamine is thought to preserve baseline respiratory parameters 44 , it is sympathomimetic and has known effects on cardiac signals such as heart rate (HR) and heart rate variability (HRV) 45 . In fact, cardiac measures alone have been suggested as potential biomarkers of treatment outcomes in patients with major depressive disorder (MDD) 45,46 .…”

Section: Ketamine Induces Altered States Of Consciousness and Reduces...mentioning

confidence: 99%

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Acute effects of subanesthetic ketamine on cerebrovascular hemodynamics in humans: A TD-fNIRS neuroimaging study

Castillo¹,

Dubois²,

Field³

et al. 2023

Preprint

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Quantifying neural activity in natural conditions (i.e. conditions comparable to the standard clinical patient experience) during the administration of psychedelics may further our scientific understanding of the effects and mechanisms of action. This data may facilitate the discovery of novel biomarkers enabling more personalized treatments and improved patient outcomes. In this single-blind, placebo-controlled study with a non-randomized design, we use time-domain functional near-infrared spectroscopy (TD-fNIRS) to measure acute brain dynamics after intramuscular subanesthetic ketamine (0.75 mg/kg) and placebo (saline) administration in healthy participants (n = 15, 8 females, 7 males, age 32.4 +/- 7.5 years) in a clinical setting. We found that the ketamine administration caused an altered state of consciousness and changes in systemic physiology (e.g. increase in pulse rate and electrodermal activity). Furthermore, ketamine led to a brain-wide reduction in the fractional amplitude of low frequency fluctuations (fALFF), and a decrease in the global brain connectivity of the prefrontal region. Lastly, we provide preliminary evidence that a combination of neural and physiological metrics may serve as predictors of subjective mystical experiences and reductions in depressive symptomatology. Overall, our studies demonstrated the successful application of fNIRS neuroimaging to study the physiological effects of the psychoactive substance ketamine and can be regarded as an important step toward larger scale clinical fNIRS studies that can quantify the impact of psychedelics on the brain in standard clinical settings.

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Section: Discussionsupporting

confidence: 93%

Section: Ketamine Induces Altered States Of Consciousness and Reduces...supporting

confidence: 91%

Section: Resultsmentioning

confidence: 99%

Section: Ketamine Induces Altered States Of Consciousness and Reduces...mentioning

confidence: 99%

See 2 more Smart Citations

Acute effects of subanesthetic ketamine on cerebrovascular hemodynamics in humans: A TD-fNIRS neuroimaging study

Castillo¹,

Dubois²,

Field³

et al. 2023

Preprint

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show abstract

“…In addition, here we omitted the 4 h following ketamine infusion to allow for the immediate effects to dissipate. Interestingly, a recent study also investigated the use of HR for response prediction to ketamine for depression: Similar to the here-reported results, Meyer et al (43) have found HR to be significantly higher in responders, supporting a possible predictive value of HR for (ketamine) treatment outcome and warranting further research into the relationship between low-dose ketamine and HR.…”

Section: Treatment Response Prediction Based On Hrsupporting

confidence: 87%

Twenty-Four-Hour Heart Rate Is a Trait but Not State Marker for Depression in a Pilot Randomized Controlled Trial With a Single Infusion of Ketamine

et al. 2021

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Background: Abnormalities of heart rate (HR) and its variability are characteristic of major depressive disorder (MDD). However, circadian rhythm is rarely taken into account when statistically exploring state or trait markers for depression.Methods: A 4-day electrocardiogram was recorded for 16 treatment-resistant patients with MDD and 16 age- and sex-matched controls before, and for the patient group only, after a single treatment with the rapid-acting antidepressant ketamine or placebo (clinical trial registration available on https://www.clinicaltrialsregister.eu/ with EUDRACT number 2016-001715-21). Circadian rhythm differences of HR and the root mean square of successive differences (RMSSD) were compared between groups and were explored for classification purposes. Baseline HR/RMSSD were tested as predictors for treatment response, and physiological measures were assessed as state markers.Results: Patients showed higher HR and lower RMSSD alongside marked reductions in HR amplitude and RMSSD variation throughout the day. Excellent classification accuracy was achieved using HR during the night, particularly between 2 and 3 a.m. (90.6%). A positive association between baseline HR and treatment response (r = 0.55, p = 0.046) pointed toward better treatment outcome in patients with higher HR. Heart rate also decreased significantly following treatment but was not associated with improved mood after a single infusion of ketamine.Limitations: Our study had a limited sample size, and patients were treated with concomitant antidepressant medication.Conclusion: Patients with depression show a markedly reduced amplitude for HR and dysregulated RMSSD fluctuation. Higher HR and lower RMSSD in depression remain intact throughout a 24-h day, with the highest classification accuracy during the night. Baseline HR levels show potential for treatment response prediction but did not show potential as state markers in this study.Clinical trial registration: EUDRACT number 2016-001715-21.

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Heart rate as a predictor of ketamine’s fast-acting antidepressant response

Arns

2021

Clinical Neurophysiology

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Predictive value of heart rate in treatment of major depression with ketamine in two controlled trials

Cited by 13 publications

References 38 publications

Acute effects of subanesthetic ketamine on cerebrovascular hemodynamics in humans: A TD-fNIRS neuroimaging study

Acute effects of subanesthetic ketamine on cerebrovascular hemodynamics in humans: A TD-fNIRS neuroimaging study

Twenty-Four-Hour Heart Rate Is a Trait but Not State Marker for Depression in a Pilot Randomized Controlled Trial With a Single Infusion of Ketamine

Heart rate as a predictor of ketamine’s fast-acting antidepressant response

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