Ketamine for chronic depression: two cautionary tales

Talbot, Jeanne; Phillips, Jennifer L.; Blier, Pierre

doi:10.1503/jpn.190073

Cited by 8 publications

(6 citation statements)

References 10 publications

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“…For some participants, hopelessness was related to the impossibility of long-term treatment because of lack of funds, which suggests that these feelings might be related both to beneficial effects of ketamine wearing off and concerns about availability of alternative treatments. Similar cases are described elsewhere, 17,35 which have contributed to suggestions that adjunctive psychosocial interventions 17 and closer monitoring of ketamine patients 35 may augment beneficial outcomes and ensure early identification of relapse. These suggestions have also been made by patients.…”

Section: Discussionsupporting

confidence: 56%

“…This is particularly important given that some authors have urged caution regarding provision of ketamine treatment getting ahead of evidence of effectiveness. 16,17 Concerns have also been expressed about the impact on patients where the treatment fails, an initial impact reverses or when patients have to cease therapy because of insufficient funds to cover the cost. 18 The current study…”

Section: Ketamine For Treatment Of Depressionmentioning

confidence: 99%

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Ketamine treatment for individuals with treatment-resistant depression: longitudinal qualitative interview study of patient experiences

et al. 2020

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Background Ketamine has recently received considerable attention regarding its antidepressant and anti-suicidal effects. Trials have generally focused on short-term effects of single intravenous infusions. Research on patient experiences is lacking. Aims To investigate the experiences over time of individuals receiving ketamine treatment in a routine clinic, including impacts on mood and suicidality. Method Twelve fee-paying patients with treatment-resistant depression (6 females, 6 males, age 21–70 years; 11 reporting suicidality and 6 reporting self-harm) who were assessed as eligible for ketamine treatment participated in up to three semi-structured interviews: before treatment started, a few weeks into treatment and ≥2 months later. Data were analysed thematically. Results Most participants hoped that ketamine would provide respite from their depression. Nearly all experienced improvement in mood following initial treatments, ranging from negligible to dramatic, and eight reported a reduction in suicidality. Improvements were transitory for most participants, although two experienced sustained consistent benefit and two had sustained but limited improvement. Some participants described hopelessness when treatment stopped working, paralleled by increased suicidal ideation for three participants. The transient nature and cost of treatment were problematic. Eleven participants experienced side-effects, which were significant for two participants. Suggestions for improving treatment included closer monitoring and adjunctive psychological therapy. Conclusions Ketamine treatment was generally experienced as effective in improving mood and reducing suicidal ideation in the short term, but the lack of longer-term benefit was challenging for participants, as was treatment cost. Informed consent procedures should refer to the possibilities of relapse and associated increased hopelessness and suicidality.

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Section: Discussionsupporting

confidence: 56%

Section: Ketamine For Treatment Of Depressionmentioning

confidence: 99%

Ketamine treatment for individuals with treatment-resistant depression: longitudinal qualitative interview study of patient experiences

et al. 2020

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“…It should also be remembered that ketamine is a potential drug of abuse, and high doses, particularly for long periods of time, can result in increased severity of the abovementioned side effects as well as severe urological side effects. 80 In addition, as pointed out in a recent paper by Talbot et al , 81 further studies on the possible risks associated with cessation of ketamine antidepressant treatment are warranted.…”

Section: Potential Adverse Effects Of Ketaminementioning

confidence: 93%

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

Matveychuk

Thomas

Swainson

et al. 2020

Therapeutic Advances in Psychopharmacology

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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“…However, to date, ECT and ketamine have not been directly compared in a large randomized trial. Despite ketamine's potential as an antidepressant intervention, the transient nature of its effects and frequent relapse of depressive symptoms that follow the cessation of infusions remain ongoing challenges [48]. This innovative trial aims to address these issues.…”

Section: Discussionmentioning

confidence: 99%

A randomized, crossover comparison of ketamine and electroconvulsive therapy for treatment of major depressive episodes: a Canadian biomarker integration network in depression (CAN-BIND) study protocol

et al. 2020

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Background: Recent evidence underscores the utility of rapid-acting antidepressant interventions, such as ketamine, in alleviating symptoms of major depressive episodes (MDE). However, to date, there have been limited head-to-head comparisons of intravenous (IV) ketamine infusions with other antidepressant treatment strategies in large randomized trials. This study protocol describes an ongoing multi-centre, prospective, randomized, crossover, non-inferiority trial comparing acute treatment of individuals meeting diagnostic criteria for a major depressive episode (MDE) with ketamine and electroconvulsive therapy (ECT) on efficacy, speed of therapeutic effects, side effects, and health care resource utilization. A secondary aim is to compare a 6-month maintenance strategy for ketamine responders to standard of care ECT maintenance. Finally, through the measurement of clinical, cognitive, neuroimaging, and molecular markers we aim to establish predictors and moderators of treatment response as well as treatment-elicited effects on these outcomes.

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Ketamine for chronic depression: two cautionary tales

Cited by 8 publications

References 10 publications

Ketamine treatment for individuals with treatment-resistant depression: longitudinal qualitative interview study of patient experiences

Ketamine treatment for individuals with treatment-resistant depression: longitudinal qualitative interview study of patient experiences

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

A randomized, crossover comparison of ketamine and electroconvulsive therapy for treatment of major depressive episodes: a Canadian biomarker integration network in depression (CAN-BIND) study protocol

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