Happiness During Low-Dose Ketamine Infusion Predicts Treatment Response: Reexploring the Adjunctive Ketamine Study of Taiwanese Patients With Treatment-Resistant Depression

Mu-Hong Chen, MD, PhDa,b,d; Wei-Chen Lin, MDa,b,d; Hui-Ju Wu, BSNb; Ya-Mei Bai, MD, PhDa,b; Cheng-Ta Li, MD, PhDa,b,d; Shih-Jen Tsai, MDa,b,d; Chen-Jee Hong, MDa,b,d; Pei-Chi Tu, MD, PhDa,b,c; Chih-Ming Cheng, MDa,b,d; and Tung-Ping Su, MDa,b,c,d,e,*

Published: November 10, 2020

Article Abstract

Background: Studies have reported that ketamine potentially increases subjective happiness in healthy volunteers. However, whether ketamine-induced happiness can predict the treatment response of ketamine infusion among patients with treatment-resistant depression (TRD) remains unknown.

Methods: Between 2012 and 2015, 71 adult patients with TRD (based on DSM-IV-TR criteria) were enrolled and randomly assigned to receive a 40-minute ketamine (0.5 mg/kg or 0.2 mg/kg) or normal saline placebo infusion. Depressive symptoms were measured using the 17-item Hamilton Depression Rating Scale. Measurements were conducted prior to infusion, at 40 and 240 minutes postinfusion, and, sequentially, on days 2 to 7 and 14 postinfusion. The visual analog scale for happiness (VASH) was used to assess happiness during infusion. The positive symptoms subscale of the Brief Psychiatric Rating Scale (BPRS-P) was used to measure the potential psychotomimetic effects of ketamine.

Results: For both the 2-factor (ketamine vs placebo) and 3-factor (ketamine 0.5 mg/kg vs 0.2 mg/kg vs placebo) models, a generalized estimating equation model indicated that infusion response type (happiness vs nonhappiness) significantly (P = .008 vs P = .002) predicted the trajectory of depressive symptoms after infusion. Changes in VASH and BPRS-P measures were not associated with each other.

Conclusions: Subjective happiness during ketamine infusion predicted the antidepressant effect of both 0.5 mg/kg and 0.2 mg/kg ketamine infusion over time. Happiness during ketamine infusion, which was not related to the psychotomimetic effect of ketamine, may be associated with the reduction of depressive symptoms during the follow-up.

Trial Registration: UMIN Clinical Trials Registry registration number: UMIN000016985

Volume: 81

Quick Links: Psychiatry

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