A response to: Repeated intranasal ketamine for treatment resistant depression: The way to go? Results from a pilot randomised controlled trial

Lee, Vincent; Archer, Shaina; Chrenek, Carson; Swainson, Jennifer

doi:10.1177/0269881118822160

Cited by 10 publications

(14 citation statements)

References 2 publications

(2 reference statements)

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“…While one RCT on intranasal ketamine 63 suggested that intranasal administration may be a viable alternative, another study 64 was aborted early due to poor tolerance to the intranasal formulation. Other reports based on clinical experience 65,66 have reported that although it remains experimental in nature, maintenance intranasal ketamine has been clinically useful in patients who have exhausted other treatment options. Studies on oral and sublingual ketamine have been the subject of a recent systematic review, 67 but the studies reviewed include wide variations in dosing and do not appear to take into account limited bioavailability of oral formulations, so may underestimate efficacy.…”

Section: Overview Of the Status Of Clinical Trials With Ketamine And mentioning

confidence: 99%

Ketamine as an antidepressant: overview of its mechanisms of action and potential predictive biomarkers

Matveychuk

Thomas

Swainson

et al. 2020

Therapeutic Advances in Psychopharmacology

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117

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Ketamine, a drug introduced in the 1960s as an anesthetic agent and still used for that purpose, has garnered marked interest over the past two decades as an emerging treatment for major depressive disorder. With increasing evidence of its efficacy in treatment-resistant depression and its potential anti-suicidal action, a great deal of investigation has been conducted on elucidating ketamine’s effects on the brain. Of particular interest and therapeutic potential is the ability of ketamine to exert rapid antidepressant properties as early as several hours after administration. This is in stark contrast to the delayed effects observed with traditional antidepressants, often requiring several weeks of therapy for a clinical response. Furthermore, ketamine appears to have a unique mechanism of action involving glutamate modulation via actions at the N-methyl-D-aspartate (NMDA) and [Formula: see text]-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, as well as downstream activation of brain-derived neurotrophic factor (BDNF) and mechanistic target of rapamycin (mTOR) signaling pathways to potentiate synaptic plasticity. This paper provides a brief overview of ketamine with regard to pharmacology/pharmacokinetics, toxicology, the current state of clinical trials on depression, postulated antidepressant mechanisms and potential biomarkers (biochemical, inflammatory, metabolic, neuroimaging sleep-related and cognitive) for predicting response to and/or monitoring of therapeutic outcome with ketamine.

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Section: Overview Of the Status Of Clinical Trials With Ketamine And mentioning

confidence: 99%

Ketamine as an antidepressant: overview of its mechanisms of action and potential predictive biomarkers

Matveychuk

Thomas

Swainson

et al. 2020

Therapeutic Advances in Psychopharmacology

Self Cite

117

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“…56 In contrast, a retrospective study of 17 patients treated clinically with up to 100 mg once or twice a week as maintenance treatment after 6 to 8 IV ketamine infusions found good tolerability and benefit in 13 patients (76%). 57 Differences in these reports likely reflect variability in treatment devices, intranasal absorption, and bioavailability of racemic ketamine. The only RCT with subcutaneous ketamine was in a small sample of geriatric patients.…”

Section: Resultsmentioning

confidence: 99%

“…46 Anecdotal reports suggest that some patients may be able to transition to intranasal or sublingual formulations of racemic ketamine for maintenance after ketamine infusions. 57…”

Section: Resultsmentioning

confidence: 99%

The Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force Recommendations for the Use of Racemic Ketamine in Adults with Major Depressive Disorder: Recommandations Du Groupe De Travail Du Réseau Canadien Pour Les Traitements De L’humeur Et De L’anxiété (Canmat) Concernant L’utilisation De La Kétamine Racémique Chez Les Adultes Souffrant De Trouble Dépressif Majeur

et al. 2020

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Objective: Patients with major depressive disorder often have limited response to first-line and second-line medications; hence, novel pharmacological treatments are needed for treatment-resistant depression (TRD). Ketamine, an N-methyl-d-aspartate (NMDA) receptor antagonist, has demonstrated rapid antidepressant effects in patients with TRD. The Canadian Network for Mood and Anxiety Treatments (CANMAT) convened a task force to review the evidence for efficacy and safety of racemic ketamine and to provide recommendations for its use in clinical practice. Methods: A systematic review was conducted with computerized search of electronic databases up to January 31, 2020 using combinations of search terms, inspection of bibliographies, and review of other ketamine guidelines and consensus statements. The level of evidence and lines of treatment were assigned according to CANMAT criteria. Recommendations were given in question–answer format. Results: Intravenous (IV) racemic ketamine given as a single infusion has Level 1 evidence for efficacy in adults with TRD. The evidence for multiple infusions, given as an acute series or as ongoing maintenance treatment, is limited to Level 3. Adverse events associated with ketamine infusions include behavioral (e.g., dissociative symptoms) and physiological (e.g., hypertension) events. There is only Level 3 or 4 evidence for non-IV formulations of racemic ketamine. Consensus recommendations are given for clinical administration of IV ketamine including patient selection, facility and personnel issues, monitoring, and maintaining response. Conclusions: Single-dose IV racemic ketamine is a third-line recommendation for adults with TRD. The need for repeated and maintenance ketamine infusions should be carefully assessed on a case-by-case basis with consideration of potential risks and benefits. Because of limited evidence for efficacy and risk for misuse and diversion, the use of oral and other formulations of racemic ketamine should be limited to specialists with ketamine-prescribing expertise and affiliations with tertiary or specialized centers.

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“…Our study sample was modest as the trial was ceased early; however, it used a blinded parallel RCT design, with rigorous attention to spray administration technique, the use of a psychoactive control, the detailed collection of safety outcomes and the evaluation of plasma ketamine concentrations. This contrasts with the report of Lee et al, in which data were collected in a clinical manner (Lee et al, 2019).…”

Section: Dear Editormentioning

confidence: 61%

A reply to comments by Lee and colleagues on: Repeated intranasal ketamine for treatment resistant depression – the way to go? Results from a pilot randomised controlled trial

et al. 2019

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A response to: Repeated intranasal ketamine for treatment resistant depression: The way to go? Results from a pilot randomised controlled trial

Cited by 10 publications

References 2 publications

Ketamine as an antidepressant: overview of its mechanisms of action and potential predictive biomarkers

Ketamine as an antidepressant: overview of its mechanisms of action and potential predictive biomarkers

A reply to comments by Lee and colleagues on: Repeated intranasal ketamine for treatment resistant depression – the way to go? Results from a pilot randomised controlled trial

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