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

Abstract

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.

Cognitive function after electroconvulsive therapy for depression: relationship to clinical response

“…The neuropsychological assessment consisted of tests involving verbal and visual memory, attention and verbal fluency/executive function (Anderson et al, 2017a(Anderson et al, , 2017b with the key outcomes reported here.…”

Ketamine and electroconvulsive therapy pairing in depression and mood disorders

“…This finding was in sharp contrast to the rapid antidepressant effect within hours or days reported when ketamine was administered alone. Anderson et al [13] also reported that two patients in the ketamine group had transient psychological effects following ECT treatments, but no evidence of serious tolerability or safety problems with ketamine given at the dose provided in the study were found. The smaller-than-planned sample size is the most important limitation of the study.…”

“…Animal and preliminary human trials suggested that the glutamate antagonist ketamine might improve reorientation and word recall after ECT and accelerate symptomatic improvement. In a recent multicentre, randomized, parallel-group study in 11 ECT suites serving inpatient and outpatient care settings in seven National Health Service trusts in the North of England published at Lancet Psychiatry; Anderson et al [13] recruited severely depressed patients, aged 18 years and older who experienced moderate or severe unipolar or bipolar depressive episodes. Patients were randomly assigned to receive ketamine (0.5 mg/kg intravenous bolus) or saline adjunctive to the anesthetic (propofol or thiopental) for the duration of their ECT course.…”

Twenty-Four-Hour Variation of Intraocular Pressure in Primary Open-Angle Glaucoma Treated with Triple Eye Drops

“…The diagnostic criteria of POAG were as follows: normal open-angle; characteristic glaucomatous optic neuropathy with diffuse or focal optic rim thinning, cupping, or nerve fiber layer defects indicative of glaucoma and corresponding visual field changes according to Anderson and Patella criteria [21]; and presence of no other ocular, rhinological, neurological, or systemic disorders potentially causing optic nerve damage. Exclusion criteria were a history of cardiac or respiratory disorders; severe corneal disease, uveitis, or previous eye surgery; and concomitant use of any systemic medication that might affect the IOP.…”