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Pilot dose–response trial of i.v. ketamine in treatment-resistant depression

R. Lai, Natalie Katalinic, Paul Glue, Andrew A Somogyi, P. Mitchell, John Leyden, Simon Harper, C. Loo

The World Journal of Biological Psychiatry September 1, 2014 DOI: 10.3109/15622975.2014.922697 (opens in new tab)

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AI-extracted from the abstract
Characteristics Double-blind, placebo-controlled, crossover pilot dose-finding study Peer reviewed
Sample size 4
Population Subjects with treatment-resistant depression
Intervention Ketamine
Dose 0.1, 0.2, 0.3, 0.4 mg/kg
Duration Doses given 1 week apart; relapse assessed within a week
Measures Montgomery–Asberg Depression Rating Scale
Topics Depression Esketamine Ketamine
Key points Three of four subjects with treatment-resistant depression responded to intravenous ketamine, two at the minimum 0.1 mg/kg dose, though all relapsed within a week. The authors report that antidepressant efficacy and psychotomimetic effects both appeared dose-related, and conclude that rapid 2-minute infusion may not be a feasible clinical approach given poor tolerability.

Abstract

Abstract Objectives. Research studies have reported impressive antidepressant effects with ketamine but significant knowledge gaps remain over the best method of administering ketamine, and the relationships between dose, antidepressant response and adverse effects. Methods. In this pilot dose-finding study, the efficacy and tolerability of ketamine given by rapid intravenous (i.v.) infusion were assessed in a double-blind, placebo-controlled, crossover design, in four subjects with treatment- resistant depression. Each subject received up to four i.v. doses of ketamine (0.1, 0.2, 0.3, 0.4 mg/kg), given over 2–5 min, 1 week apart, and one randomly inserted placebo treatment. Results. Three of four subjects achieved antidepressant response (≥ 50% decrease in Montgomery–Asberg Depression Rating Scale scores), two at the minimum 0.1 mg/kg dose, though all relapsed within a week. For two subjects, the greatest improvement occurred at the highest dose received. Rapid infusion over 2 min led to significant adverse psychotomimetic effects which also increased proportionately with ketamine dosage. Conclusions. This is the first trial to present dose–response data of ketamine efficacy and psychomimetic effects in depressed subjects. Antidepressant efficacy may be dose-related. Psychotomimetic effects were dose-related. Rapid infusion over 2 min may not be a feasible clinical approach to treatment, given poor tolerability.

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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