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Intraoperative ketamine for prevention of depressive symptoms after major surgery in older adults: an international, multicentre, double-blind, randomised clinical trial.

George A. Mashour, A Ben Abdallah, K O Pryor, R El-Gabalawy, Phillip E. Vlisides, E Jacobsohn, Eric J Lenze, Hannah R. Maybrier, R A Veselis, Michael S. Avidan

British Journal of Anaesthesia November 2018 DOI: 10.1016/j.bja.2018.03.030 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Randomized controlled trial Double-blind Peer reviewed
Sample size 670
Population Patients aged 60 years or older undergoing major surgery with general anesthesia
Interventions Ketamine saline placebo
Dose 0.5 mg kg-1 (Lo-K) or 1.0 mg kg-1 (Hi-K)
Duration Assessments before operation, on postoperative day 3, and on postoperative day 30
Measures Patient Health Questionnaire-8
Topics Depression Ketamine Esketamine
Keywords Anti-depressant Surgery
Registration NCT01690988
Key findings Intraoperative subanesthetic ketamine did not prevent or improve symptoms suggestive of depression after major surgery; the proportion with such symptoms on postoperative day 3 was 17.5% with ketamine versus 14.7% with placebo, a non-significant difference. Depressive symptoms increased from 9.6% preoperatively to 16.6% on day 3 and decreased to 11.9% by day 30, with about half of affected patients having no prior depression history.

Abstract

Ketamine is a general anaesthetic with anti-depressant effects at subanaesthetic doses. We hypothesised that intraoperative administration of ketamine would prevent or mitigate postoperative depressive symptoms in surgical patients. We conducted an international, randomised clinical trial testing the effects of intraoperative administration of ketamine [0.5 mg kg-1 (Lo-K) or 1.0 mg kg-1 (Hi-K)] vs control [saline placebo (P)] in patients ≥60 yr old undergoing major surgery with general anaesthesia. We administered the Patient Health Questionnaire-8 before the operation, on postoperative day (POD) 3 (primary outcome), and on POD30 to assess depressive symptoms, a secondary outcome of the original trial. There was no significant difference on POD3 in the proportion of patients with symptoms suggestive of depression between the placebo [23/156 (14.7%)] and combined ketamine (Lo-K plus Hi-K) [61/349 (17.5%)] groups [difference = -2.7%; 95% confidence interval (CI), 5.0% to -9.4%; P=0.446]. Of the total cohort, 9.6% (64/670; 95% CI, 7.6-12.0%) had symptoms suggestive of depression before operation, which increased to 16.6% (84/505; 95% CI, 13.6-20.1%) on POD3, and decreased to 11.9% (47/395; 95% CI, 9.1-15.5%) on POD30. Of the patients with depressive symptoms on POD3 and POD30, 51% and 49%, respectively, had no prior history of depression or depressive symptoms. Major surgery is associated with new-onset symptoms suggestive of depression in patients ≥60 yr old. Intraoperative administration of subanaesthetic ketamine does not appear to prevent or improve depressive symptoms. NCT01690988.

Comparable studies

Other randomized controlled trials on ketamine for depression, most cited first.

Study Year Design Participants
Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial Patients with treatment-resistant major depression experiencing a major depressive episode 2013 Randomized controlled trial n = 73
Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study Adults with moderate to severe nonpsychotic depression and a history of nonresponse to... 2019 Phase 3, double-blind, active-controlled, multicenter randomized controlled trial n = 227
Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression Adults with treatment-resistant depression who achieved stable remission or stable... 2019 Phase 3, multicenter, double-blind, randomized withdrawal study n = 297
Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression Adults with DSM-IV-TR diagnosis of major depressive disorder and history of inadequate... 2017 Phase 2, double-blind, doubly randomized, delayed-start, placebo-controlled study n = 67
Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study Depressed patients at imminent risk for suicide 2018 Randomized controlled trial n = 68

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