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Comparative study of low-dose ketamine infusion and repetitive transcranial magnetic stimulation in treatment-resistant depression: A posthoc pooled analysis of two randomized, double-blind, placebo-controlled studies.

Mu-Hong Chen, Chih-Ming Cheng, Cheng-Ta Li, S. Tsai, Wei-Chen Lin, Ya-Mei Bai, T. Su

Psychiatry Research July 1, 2022 DOI: 10.1016/j.psychres.2022.114749 (opens in new tab)

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AI-extracted from the abstract
Characteristics Posthoc analysis of two randomized controlled trials Placebo-controlled Double-blind Peer reviewed
Sample size 153
Population Patients with treatment-resistant depression
Interventions Ketamine intermittent theta-burst stimulation (iTBS) 10-Hz rTMS sham stimulation normal saline
Dose 0.5 mg/kg ketamine
Duration Follow-up up to 3 months
Measures 17-item Hamilton Rating Scale for Depression (HDRS), HDRS item 3
Topics Depression Esketamine Ketamine
Key findings Low-dose ketamine infusion produced a prominent antidepressant effect at Day 7, while iTBS and 10-Hz rTMS effects accumulated from Day 7 to 14. Ketamine and iTBS were superior for suicidal symptoms. rTMS effects persisted up to 3 months, but a single ketamine infusion's effect did not last beyond one month. The authors contend both treatments should be included in treatment-resistant depression care, applied in different clinical situations.

Abstract

Background: This posthoc analysis compared the antidepressant and antisuicidal effects of low-dose ketamine infusion with those of repetitive transcranial magnetic stimulation (rTMS) on treatment-resistant depression (TRD).

Methods: In the ketamine infusion trial, 48 patients with TRD were randomized to receive a single infusion of 0.5 mg/kg ketamine or normal saline. In the rTMS trial, 105 patients were randomly assigned to intermittent theta-burst stimulation (iTBS), 10-Hz rTMS, or sham stimulation. The 17-item Hamilton Rating Scale for Depression (HDRS) was administered.

Results: The antidepressant effect was prominent at Day 7 postinfusion in the ketamine group but steadily accumulated with the treatment duration from Day 7 to 14 in the iTBS and 10-Hz rTMS groups, regardless of the level of treatment resistance (all p < .01). Low-dose ketamine infusion and iTBS exerted superior effects on suicidal symptoms (HDRS item 3) than the other three groups (p < .001). The antidepressant effect of iTBS/10-Hz rTMS may persist for up to 3 months; however, the antidepressant effect of a single low-dose ketamine infusion did not persist over a month.

Discussion: Both low-dose ketamine infusion and rTMS/TBS must be included in TRD treatment but may be applied in different clinical situations.

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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