Simultaneous EEG/fMRI recorded during ketamine infusion in patients with major depressive disorder

McMillan, Rebecca; Sumner, Rachael L.; Forsyth, Anna; Campbell, Doug; Malpas, Gemma; Maxwell, Elizabeth; Deng, Carolyn; Hay, John; Ponton, Rhys; Sundram, Frederick; Muthukumaraswamy, Suresh

doi:10.1016/j.pnpbp.2019.109838

Cited by 41 publications

(31 citation statements)

References 50 publications

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“…However, most of the biomarker work conducted to date uses markers collected hours to days after ketamine administration, well past the time points associated with ketamine's dissociative effects and therefore not connected to specific dissociative experiences. In contrast, real-time data collection during ketamine administration, such as during MEG or fMRI 74 , could provide insights into the activation of specific neural circuits during dissociative experiences associated with ketamine administration. At the same time, cellular and molecular studies can provide additional insights into not only the mechanisms of RAADs but also dissociation and other psychotomimetic effects.…”

Section: Dissociation or Other Psychotomimetic Effects Associated Witmentioning

confidence: 99%

The role of dissociation in ketamine’s antidepressant effects

2020

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Ketamine produces immediate antidepressant effects and has inspired research into next-generation treatments. Ketamine also has short term dissociative effects, in which individuals report altered consciousness and perceptions of themselves and their environment. However, whether ketamine’s dissociative side effects are necessary for its antidepressant effects remains unclear. This perspective examines the relationship between dissociative effects and acute and longer-lasting antidepressant response to ketamine and other N-methyl-D-aspartate (NMDA) receptor antagonists. Presently, the literature does not support the conclusion that dissociation is necessary for antidepressant response to ketamine. However, further work is needed to explore the relationship between dissociation and antidepressant response at the molecular, biomarker, and psychological levels.

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Section: Dissociation or Other Psychotomimetic Effects Associated Witmentioning

confidence: 99%

The role of dissociation in ketamine’s antidepressant effects

2020

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“…Compared to the substantial number of studies focused on ketamine‐induced brain alterations in patients with unipolar depression (Chen et al., 2019; McMillan et al., 2019; Morris et al., 2020; Nugent et al., 2019; Zacharias et al., 2020), only a few studies have investigated the functional brain alterations associated with ketamine augmentation in patients with TRBPD. Recently, Diazgranados et al conducted a 2‐week study to investigate the antidepressant effects of ketamine infusions in patients with TRBPD and found that 71% of patients with TRBPD responded to ketamine augmentation (Diazgranados et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Transient effects of multi‐infusion ketamine augmentation on treatment‐resistant depressive symptoms in patients with treatment‐resistant bipolar depression – An open‐label three‐week pilot study

et al. 2020

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Introduction While the psychiatric benefits of ketamine have been verified through clinical trials, there is limited information about ketamine augmentation in patients with treatment‐resistant bipolar depression (TRBPD). Hence, in the present study, we investigate the therapeutic efficacy and functional brain alterations associated with multi‐infusion ketamine augmentation in patients with TRBPD. Methods The present three‐week study included 38 patients with TRBPD, all of whom received a series of nine ketamine injections over the study period. The Hamilton Depression Rating Scale (HAMD) was used to assess the effects of multi‐infusion ketamine combined with mood stabilizers. Brain function was evaluated by global functional connectivity density (gFCD). Results Adjunctive treatment with multiple infusions of ketamine, when combined with a mood stabilizer, could effectively alleviate depressive symptoms for one week, yet the symptoms began to relapse during the second week. Functional brain alterations were detected via gFCD. Specifically, gFCD reductions were mainly found in the bilateral insula, right caudate nucleus, and bilateral inferior frontal gyrus, while increased gFCD was mainly located in the bilateral postcentral gyrus, subgenual anterior cingulate cortex, bilateral thalamus, and cerebellum. Although gFCD alterations were sustained for up to three weeks after the first ketamine infusion, the antidepressant effects of ketamine augmentation sharply declined from the end of the second week of treatment. Conclusions Multi‐infusion ketamine augmentation can rapidly alleviate depressive symptoms in patients with TRBPD. The clinical effects were primarily visible in the first week after treatment and partially sustained for two weeks; however, the therapeutic effects and related functional brain alterations sharply decreased from the end of the second week. Based on these findings, we demonstrated that the clinical efficacy and functional brain alterations induced by ketamine augmentation are transient.

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“…0.5 mg/kg responders had lower relative theta and alpha power at baseline summed across all electrodes, and, after treatment, they had higher theta power in Fp1 and Fp2, findings not observed in 0.2 mg/kg responders. In McMillan et al's simultaneous EEG and fMRI study 22 discussed above, from the EEG perspective, a trending relationship was observed with increased frontal theta power and antidepressant response. Yet, like their fMRI results, these were sensitive to noise correction, calling for the standardization of processing techniques, but these preliminary findings corroborates Zehong and colleagues's increased theta power in ketamine responders.…”

Section: Electroencephalography (Eeg)mentioning

confidence: 92%

“…21 Interestingly, McMillan et al recorded EEG and fMRI simultaneously during ketamine infusion and only found significant correlations with treatment response when associating the two modalities. 22 In their study, BOLD signal variance explained by high gamma power in the insula, ACC, and posterior cingulate cortex (PCC) correlated with antidepressant response, where responders had a smaller change in BOLD signal than non-responders. They were also unable to replicate Downey et al's increased sgACC BOLD signal.…”

Section: Functional Magnetic Resonance Imaging (Fmri)mentioning

confidence: 99%

Biomarkers of ketamine’s antidepressant effect: a clinical review of genetics, functional connectivity, and neurophysiology

Alario

Niciu

2021

Chronic Stress

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Major depressive disorder (MDD) is one of the leading causes of morbidity and all-cause mortality (including suicide) worldwide, and, unfortunately, first-line monoaminergic antidepressants and evidence-based psychotherapies are not effective for all patients. Subanesthetic doses of the N-methyl-D-aspartate receptor antagonists and glutamate modulators ketamine and S-ketamine have rapid and robust antidepressant efficacy in such treatment-resistant depressed patients (TRD). Yet, as with all antidepressant treatments including electroconvulsive therapy (ECT), not all TRD patients adequately respond, and we are presently unable to a priori predict who will respond or not respond to ketamine. Therefore, antidepressant treatment response biomarkers to ketamine have been a major focus of research for over a decade. In this article, we review the evidence in support of treatment response biomarkers, with a particular focus on genetics, functional magnetic resonance imaging, and neurophysiological studies, i.e. electroencephalography and magnetoencephalography. The studies outlined here lay the groundwork for replication and dissemination.

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Simultaneous EEG/fMRI recorded during ketamine infusion in patients with major depressive disorder

Cited by 41 publications

References 50 publications

The role of dissociation in ketamine’s antidepressant effects

The role of dissociation in ketamine’s antidepressant effects

Transient effects of multi‐infusion ketamine augmentation on treatment‐resistant depressive symptoms in patients with treatment‐resistant bipolar depression – An open‐label three‐week pilot study

Biomarkers of ketamine’s antidepressant effect: a clinical review of genetics, functional connectivity, and neurophysiology

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