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

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 thetaburst 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/10Hz 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.