Ketamine Anesthesia, Efficacy of Electroconvulsive Therapy, and Cognitive Functions in Treatment-Resistant Depression

Rybakowski, Janusz; Bodnar, Anna; Krzywotulski, Milosz; Chłopocka-Woźniak, M; Michalak, Michał; Rosada-Kurasińska, Jowita; Bartkowska-Śniatkowska, Alicja

doi:10.1097/yct.0000000000000317

Cited by 35 publications

(30 citation statements)

References 16 publications

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“…The largest published randomised trial so far 31 has reported that ketamine (0·3 mg/kg) as an adjunct to propofol significantly reduced the effect of ECT on a range of aspects of memory using a modified Chinese version of the Wechsler Memory Scale. By contrast, Rybakowski and colleagues, 32 in a non-randomised prospective study, found that ketamine (1–1·5 mg/kg) as an adjunct to thiopental at alternate ECT sessions worsened verbal memory and had a trend to worsen letter fluency, but did not affect executive function, visual memory, or digit span compared with thiopental alone. Similarly, results for reorientation after ECT are conflicting; one randomised trial found adjunctive ketamine (0·3 mg/kg) led to more rapid re-orientation compared with propofol alone, 33 while a randomised crossover study with ketamine (1 mg/kg) delayed reorientation compared with methohexital 34 .…”

Section: Discussionmentioning

confidence: 90%

Ketamine augmentation of electroconvulsive therapy to improve neuropsychological and clinical outcomes in depression (Ketamine-ECT): a multicentre, double-blind, randomised, parallel-group, superiority trial

Anderson

Blamire

Branton

et al. 2017

The Lancet Psychiatry

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SummaryBackgroundThe use of electroconvulsive therapy (ECT) is limited by concerns about its cognitive adverse effects. Preliminary evidence suggests that administering the glutamate antagonist ketamine with ECT might alleviate cognitive adverse effects and accelerate symptomatic improvement; we tested this in a randomised trial of low-dose ketamine.MethodsIn this multicentre, randomised, parallel-group study in 11 ECT suites serving inpatient and outpatient care settings in seven National Health Service trusts in the North of England, we recruited severely depressed patients, who were diagnosed as having unipolar or bipolar depressive episodes defined as moderate or severe by DSM-IV criteria, aged at least 18 years, and were able and willing to provide written consent to participate in the study. Patients were randomly assigned (1:1) to ketamine (0·5 mg/kg intravenous bolus) or saline adjunctive to the anaesthetic for the duration of their ECT course. Patients and assessment and ECT treatment teams were masked to treatment allocation, although anaesthetists administering the study medication were not. We analysed the primary outcome, Hopkins Verbal Learning Test-Revised delayed verbal recall (HVLT-R-DR) after four ECT treatments, using a Gaussian repeated measures model in all patients receiving the first ECT treatment. In the same population, safety was assessed by adverse effect monitoring. This trial was registered with International Standard Randomised Controlled Trial Number, number ISRCTN14689382.FindingsBetween early December, 2012, and mid-June, 2015, 628 patients were screened for eligibility, of whom 79 were randomly assigned to treatment (40 in the ketamine group vs 39 in the saline group). Ketamine (mean 5·17, SD 2·92), when compared with saline (5·54, 3·42), had no benefit on the primary outcome (HVLT-R-DR; difference in means −0·43 [95% CI −1·73 to 0·87]). 15 (45%) of 33 ketamine-treated patients compared with 10 (27%) of 37 patients receiving saline experienced at least one adverse event which included two (6%) of 33 patients who had ketamine-attributable transient psychological effects. Psychiatric adverse events were the most common in both groups (six [27%] of 22 adverse events in the ketamine group vs seven [54%] of 13 in the saline group).InterpretationNo evidence of benefit for ketamine was found although the sample size used was small; however, the results excluded greater than a small to moderate benefit with 95% confidence. The results do not support the use of adjunctive low-dose ketamine in routine ECT treatment.FundingNational Institute for Health Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme, an MRC and NIHR partnership.

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Section: Discussionmentioning

confidence: 90%

Ketamine augmentation of electroconvulsive therapy to improve neuropsychological and clinical outcomes in depression (Ketamine-ECT): a multicentre, double-blind, randomised, parallel-group, superiority trial

Anderson

Blamire

Branton

et al. 2017

The Lancet Psychiatry

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“…It is worth noting that although significant reductions in depressive symptoms were associated with pre-ECT infusions of ketamine, these improvements were minimal. In addition, a randomized, controlled trial of MDD patients who received pre-ECT ketamine (1–1.5 mg/kg at ECT sessions 2 and 3 or 1–1.5 mg/kg at ECT sessions 2, 4, 6, 8, 10) or thiopental (2–3 mg/kg for all ECT sessions) found that depressive symptom severity was lower after the last ECT session in the group that received ketamine prior to the five ECT sessions than in the group that received only thiopental for all ECT sessions [96], suggesting that a greater frequency of paired ketamine and ECT may offer more clinical benefit than a single pre-ECT ketamine infusion. In contrast, another study series compared pre-ECT infusions of ketamine (1 mg/kg), thiopental (4 mg/kg), or both agents; the investigators found that depression symptom scores improved for all groups (as assessed by the HAM-D) and no statistically significant differences were observed between groups [97].…”

Section: Glutamatergic Synergism and The Maintenance Of Ketamine’smentioning

confidence: 99%

Ketamine and Beyond: Investigations into the Potential of Glutamatergic Agents to Treat Depression

Lener

Kadriu

Zarate

2017

Drugs

117

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Clinical and preclinical studies suggest that dysfunction of the glutamatergic system is implicated in mood disorders such as major depressive disorder (MDD) and bipolar depression. In clinical studies of individuals with MDD and bipolar depression, rapid reductions in depressive symptoms have been observed in response to subanesthetic-dose ketamine, an agent whose mechanism of action involves the modulation of glutamatergic signaling. The findings from these studies have prompted the repurposing and/or development of other glutamatergic modulators for antidepressant efficacy, both as monotherapy or as an adjunct to conventional monoaminergic antidepressants. This review will highlight the evidence supporting the antidepressant effects of subanesthetic-dose ketamine as well as other glutamatergic modulators, such as D-cycloserine (DCS), riluzole, CP-101,606, CERC-301 (previously known as MK-0657), basimglurant, JNJ-40411813, dextromethorphan, nitrous oxide (N2O), GLYX-13, and esketamine.

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“…1, Table 1). [9][10][11][12][13][14][15][16][17][18] These trials comprised 602 participants with a major depressive episode (ketamine group n = 333, comparator group n = 269). One study was retained despite important methodological concerns, including contradictory statements as to whether the trial was a single-or double-blind RCT, 14 and therefore analyses were repeated excluding this trial.…”

Section: Resultsmentioning

confidence: 99%

Adjunctive ketamine in electroconvulsive therapy: Updated systematic review and meta-analysis

et al. 2017

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Electroconvulsive therapy (ECT) remains one of the most effective treatments for refractory depression. Ketamine has gained increasing attention for use during ECT in the light of evidence supporting subanaesthetic ketamine's antidepressant properties. Ketamine is a prototype rapid-acting antidepressant for which preclinical data suggest both N-methyl-D-aspartate (NMDA) receptor and non-NMDA receptor-dependent mechanisms. 1,2 In depressed humans, meta-analyses of randomised placebo-controlled trials employing intravenous ketamine provide strong evidence of antidepressant efficacy, 3,4 and other routes of administration have also garnered randomised controlled evidence of efficacy. 5 Moreover, ketamine results in widespread increases in brain-derived neurotrophic factor, 1 which is a putative mechanism underlying ECT's effects, despite conflicting evidence. 6 We previously reported a preliminary systematic review and meta-analysis of randomised controlled trials (RCTs) using ketamine in ECT, which found increased seizure duration, but not efficacy for ketamine as an adjunct. 7 However, our report involved a small number of trials and patients, and furthermore considered trials employing either a course of ECT or a single session. Few trials examined cognitive function. Moreover, a clinically important source of heterogeneity was concomitant anaesthetic administration, an important consideration as barbiturate anaesthetic compounds may counteract ketamine's antidepressant effects. 8 In light of these limitations, and given that several studies have since been published, we sought to update our systematic review and meta-analysis, focusing on RCTs involving an index course of ECT. MethodThe study was conducted following the Preferred Reporting Items for Systematic Meta-Analyses (PRISMA) guidelines, and the protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD42016043909). Search strategyWe searched Medline, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception until 30 July 2016. The search procedures are described in online supplement DS1. We also reviewed the references of included studies for unidentified RCTs. Study selectionInclusion criteria were as follows:(a) study validity: random allocation, double-blind, controlled, parallel arm design;(b) sample characteristics: a diagnosis of primary major depressive episode according to DSM-IV or ICD criteria;

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Ketamine Anesthesia, Efficacy of Electroconvulsive Therapy, and Cognitive Functions in Treatment-Resistant Depression

Abstract: The addition of ketamine may be connected with better antidepressant efficacy of ECT, compared with only thiopental anesthesia. However, patients with added ketamine had worse results on some of the indices measuring verbal memory.

Cited by 35 publications

References 16 publications

Ketamine augmentation of electroconvulsive therapy to improve neuropsychological and clinical outcomes in depression (Ketamine-ECT): a multicentre, double-blind, randomised, parallel-group, superiority trial

Ketamine augmentation of electroconvulsive therapy to improve neuropsychological and clinical outcomes in depression (Ketamine-ECT): a multicentre, double-blind, randomised, parallel-group, superiority trial

Ketamine and Beyond: Investigations into the Potential of Glutamatergic Agents to Treat Depression

Adjunctive ketamine in electroconvulsive therapy: Updated systematic review and meta-analysis

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