Early symptomatic improvements as a predictor of response to repeated-dose intravenous ketamine: Results from the Canadian Rapid Treatment Center of Excellence

Lipsitz, Orly; McIntyre, Roger S.; Rodrigues, Nelson B.; Kaster, Tyler S.; Danielle, S.; Brietzke, Elisa; Gill, Hartej; Nasri, Flora; Lin, Kangguang; Subramaniapillai, Mehala; Kratiuk, Kevin; Teopiz, Kayla M.; Lui, Leanna M.W.; Lee, Yena; Ho, Roger; Shekotikhina, Margarita; Mansur, Rodrigo B.; Rosenblat, Joshua D.

doi:10.1016/j.pnpbp.2020.110126

Cited by 13 publications

(3 citation statements)

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“…Multiple clinical studies have reported the maintenance antidepressant effects of repeat sub-anesthetic dose intravenous (IV) ketamine for up to 6 weeks, with replicated large effect sizes [9,[12][13][14]. Compared to conventional antidepressants, IV ketamine is differentiated by (1) efficacy in patients with TRD, (2) a relatively rapid onset of therapeutic effect, and (3) preliminary evidence for reducing suicidality [10,15]. From a tolerability and safety perspective, an additional, albeit not treatment-limiting concern with ketamine is the potential for dissociation, as well as vasopressor effects [16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Strategies to Prolong Ketamine’s Efficacy in Adults with Treatment-Resistant Depression

et al. 2021

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Introduction Ketamine treatment is capable of significant and rapid symptom improvement in adults with treatment-resistant depression (TRD). A limitation of ketamine treatment in TRD is the relatively short duration of time to relapse (e.g., median 2–4 weeks). The objective of the systematic review herein is to identify strategies capable of prolonging the acute efficacy of ketamine in adults with TRD. Methods PubMed/MEDLINE databases were searched from inception to December 2020 for clinical studies written in English using the following key terms: ketamine, prolong, and depression. A total of 454 articles were identified from the literature search which included all clinical studies regarding prolonging the antidepressant effects of ketamine. Twenty-two articles were included: ten randomized controlled trials (RCTs), eight prospective open-label trials, one retrospective chart review, and three case reports. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used for data extraction. The primary outcome was prolonged effect, defined as statistically significant antidepressant effects following acute ketamine treatment. Results A total of 454 articles were identified, and 22 articles were included. Different treatment modalites including pharmacological interventions, manualized-based psychotherapies, electroconvulsive therapy, transcranial magnetic stimulation, and intravenous monotherapy were examined to determine their impact on the prolongation of antidepressant effects following acute ketamine treatment. No treatment modality, other than repeat-dose IV ketamine, has demonstrated ability to significantly prolong the acute efficacy of IV ketamine in TRD. Conclusion Hitherto, available open-label data and controlled trial data support repeat administration of IV ketamine as an effective strategy to prolong the efficacy of ketamine’s antidepressant effects (although not the focus of the study herein, maintenance repeat-dose esketamine treatment is proven effective in esketamine responders). There is a need to identify multimodality strategies that are safe and capable of prolonging the efficacy of ketamine in adults with TRD.

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Section: Introductionmentioning

confidence: 99%

Strategies to Prolong Ketamine’s Efficacy in Adults with Treatment-Resistant Depression

et al. 2021

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“…The abbreviated form of the Quick Inventory of Depressive Symptoms (QIDS-SR16) by Rush et al is a 16-item patientrated instrument that has been shown to be sensitive change in patients undergoing RAAD treatment (39,40). In both studies, participating patients completed the QIDS-SR16 ∼2 days after each IV ketamine infusion.…”

Section: Ids/qids-srmentioning

confidence: 99%

Recommendations for selection and adaptation of rating scales for clinical studies of rapid-acting antidepressants

Yavorsky¹,

Ballard²,

Opler³

et al. 2023

Front. Psychiatry

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The novel mechanisms of action (MOA) derived from some recently introduced molecular targets have led to regulatory approvals for rapid acting antidepressants (RAADs) that can generate responses within hours or days, rather than weeks or months. These novel targets include the N-methyl-D-glutamate receptor antagonist ketamine, along with its enantiomers and various derivatives, and the allosteric modulators of gamma-aminobutyric acid (GABA) receptors. There has also been a strong resurgence in interest in psychedelic compounds that impact a range of receptor sites including D1, 5-HT7, KOR, 5-HT5A, Sigma-1, NMDA, and BDNF. The RAADs developed from these novel targets have enabled successful treatment for difficult to treat depressed individuals and has generated a new wave of innovation in research and treatment. Despite the advances in the neurobiology and clinical treatment of mood disorders, we are still using rating instruments that were created decades ago for drugs from a different era (e.g., The Hamilton and Montgomery-Åsberg depression rating scales, HDRS, and MADRS) continue to be used. These rating instruments were designed to assess mood symptoms over a 7-day time frame. Consequently, the use of these rating instruments often requires modifications to address items that cannot be assessed in short time frames, such as the sleep and appetite items. This review describes the adaptative approaches that have been made with the existing scales to meet this need and examines additional domains such as daily activities, side effects, suicidal ideation and behavior, and role functioning. Recommendations for future studies are described, including the challenges related to implementation of these adapted measures and approaches to mitigation.

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“…Ακόμη όμως κι αν δεν παρατηρηθεί αυτή η ταχεία αρχική βελτίωση κατά την πρώτη SC χορήγηση, η πιθανότητα περαιτέρω ύφεσης της καταθλιπτικής συμπτωματολογίας εξακολουθεί να είναι αρκετά πιθανή μετά από την τέταρτη διαδοχική χορήγηση. 32 Γενικά, ασθενείς που δεν ανταποκρίνονται επαρκώς ύστερα από τη χορήγηση της πρώτης δόσης εσκεταμίνης, εξακολουθούν να έχουν σημαντικές πιθανότητες βελτίωσης ύστερα από κάθε ακόλουθη δόση που τους χορηγείται SC. 33 Οι διαπιστώσεις αυτές αφορούν κυρίως σε ασθενείς με ανθεκτική στη θεραπεία κατάθλιψη μιας και δεν υπάρχουν μέχρι τώρα αρκετά δεδομένα που να αφορούν στη ΔΚ.…”

Section: ταχεία βελτίωση ύστερα από την πρώτη υποδόρια ένεση εσκεταμίνης και η σχέση της με την περαιτέρω ύφεση της καταθλιπτικής συμπτωμunclassified

The role of ketamine in the treatment of treatment-resistant bipolar depression

Karakatsoulis¹,

Tsapakis²,

Fountoulakis³

2021

Psychiatriki

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ΠΕΡΙΛΗΨΗΗ ανθεκτικότητα στη θεραπεία που παρουσιάζει συχνά η διπολική κατάθλιψη, δημιουργεί την ανάγκη για την ανάπτυξη αποτελεσματικότερων μέσων αντιμετώπισής της. Στο πλαίσιο αυτό ερευνάται κατά τα τελευταία έτη η αποτελεσματικότητα τόσο της κεταμίνης όσο και του S-εναντιομερούς της. Η ευκολία της ενδορρινικής έναντι της ενδοφλεβίου οδού χορήγησης της εσκεταμίνης οδήγησε στην έγκρισή της (από το 2019) ως θεραπευτική επιλογή στην ανθεκτική στη θεραπεία κατάθλιψη. Στους μείζονες κινδύνους που ενέχει η θεραπεία με κεταμίνη, περιλαμβάνονται η εμφάνιση ψυχωτικού τύπου συμπτωματολογίας, η πιθανότητα κατάχρησης κι εξάρτησης ύστερα από επανειλημμένη χρήση και η παροδική αλλά μη αμελητέα μεταβολή της αρτηριακής πίεσης και του καρδιακού ρυθμού, καθώς και η δυνητική τοξικότητα για το ουροθήλιο και το ήπαρ. Οι κίνδυνοι αυτοί ελαχιστοποιούνται όταν η θεραπεία δεν υπερβαίνει το ενδεδειγμένο δοσολογικό εύρος και διενεργείται από έμπειρο υγειονομικό προσωπικό. Επιπλέον, οι δυνητικοί αυτοί κίνδυνοι φαίνεται να αντισταθμίζονται αρκούντως από την αποτελεσματικότητα της κεταμίνης-εσκεταμίνης σε ένα ευρύ φάσμα συμπτωμάτων του καταθλιπτικού συνδρόμου, μεταξύ των οποίων συμπεριλαμβάνονται η ανηδονία, το συνοδό άγχος, η γνωσιακή έκπτωση, η αυτοκτονικότητα και η γενική λειτουργικότητα. Ωστόσο, η ανασκόπηση της τρέχουσας βιβλιογραφίας αναδεικνύει την ανάγκη εκπόνησης περισσότερων μελετών ώστε να αξιολογηθεί η συμπεριφορά του φαρμάκου σε μελέτες φάσης 4 καθώς και την εστίαση της μελλοντικής έρευνας στις μεθόδους επιμήκυνσης της διάρκειας του θεραπευτικού αποτελέσματος.

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Early symptomatic improvements as a predictor of response to repeated-dose intravenous ketamine: Results from the Canadian Rapid Treatment Center of Excellence

Cited by 13 publications

References 43 publications

Strategies to Prolong Ketamine’s Efficacy in Adults with Treatment-Resistant Depression

Strategies to Prolong Ketamine’s Efficacy in Adults with Treatment-Resistant Depression

Recommendations for selection and adaptation of rating scales for clinical studies of rapid-acting antidepressants

The role of ketamine in the treatment of treatment-resistant bipolar depression

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