The relationship between subjective effects induced by a single dose of ketamine and treatment response in patients with major depressive disorder: a systematic review

Introduction

Mathai and colleagues frame ketamine as an N‑methyl‑D‑aspartate receptor (NMDAR) antagonist with rapid antidepressant effects that are hypothesised to arise from modulation of glutamate transmission, AMPA receptor potentiation and downstream neuroplastic changes. The introduction notes ketamine's broader pharmacology, neuroimaging findings, and historical links to psychedelic research; it highlights that ketamine can occasion pronounced alterations of consciousness that resemble, in some respects, experiences induced by serotonergic psychedelics. The authors point out that while dissociative and psychotomimetic effects are routinely measured in ketamine trials (often as adverse events), it remains unclear whether and how these subjective states relate to antidepressant benefit. This systematic review therefore set out to examine empirical evidence for a relationship between single‑dose ketamine‑induced subjective experiences and subsequent change in depression scores in adults with Major Depressive Disorder (MDD). Specifically, the investigators sought studies that measured subjective effects with validated psychometric scales (for example the Clinician‑Administered Dissociative States Scale, CADSS; the Brief Psychiatric Rating Scale, BPRS; and the 5‑Dimensional Altered States of Consciousness Rating Scale, 5D‑ASC) and statistically correlated those measures with depression outcomes following a single ketamine exposure. The goal was to clarify whether hallucinogenic or dissociative states contribute meaningfully to ketamine’s antidepressant mechanism or clinical effect.