Predictors of response to repeated ketamine infusions in depression with suicidal ideation: An ROC curve analysis

Abstract

Background: Ketamine has rapid-acting antidepressant and antisuicidal properties, while a proportion of patients do not adequately achieve a complete response to ketamine. Our aim was to explore the applicability of using clinical factors and serum tryptophan (TRP) metabolites to predict the response to six doses of ketamine for depression with suicidal ideation.

Methods: Seventy-three depressed patients with suicidal ideation received a thrice-weekly infusion regimen of subanaesthetic doses of ketamine. Clinical symptoms were assessed by the Montgomery-Asberg Depression Rating Scale (MADRS), Beck's Scale for Suicide Ideation (SSI) and Patient Health Questionnaire-9 (PHQ-9), and serum levels of TRP, kynurenine (KYN) and kynurenic acid (KYNA) were detected by liquid chromatography-tandem mass spectrometry at baseline and day 1 (1 day after the first infusion). The potential predictors of response was evaluated using receiver operating characteristic (ROC) curve analyses.

Results: The area under the curve (AUC = 0.959) implied a good accuracy of the combination of early clinical response and day 1 KYN and KYNA levels as a predictor of acute antidepressant response. The combination of early clinical response and day 1 KYNA levels showed moderate discrimination of acute antisuicidal response with an AUC of 0.825 and short-term antidepressant response with an AUC of 0.813.

Limitations: The patients continued receiving previous medications during ketamine treatment, which may have impacted the TRP metabolites.

Conclusion: The combination of early clinical response and TRP metabolites at the early stage of repeated ketamine treatment could be considered an eligible predictor for acute- and short-term response for treating depression with suicidal ideation.

Keywords: Ketamine; Kynurenic acid; Prediction; Suicide.