Trial PaperAnxiety DisordersDepressive DisordersMajor Depressive Disorder (MDD)Treatment-Resistant Depression (TRD)Neuroimaging & Brain MeasuresKetamine

A qualitative and quantitative account of patient’s experiences of ketamine and its antidepressant properties

In 32 people with major depressive disorder given subanaesthetic ketamine versus an active placebo, larger 24‑hour antidepressant responses correlated with psychedelic dimensions (spirituality, unity, insight) and qualitative interviews documented pervasive perceptual changes, loss of control, emotional shifts and a lasting afterglow that altered perspectives on life and treatment. These findings give preliminary evidence that the acute psychedelic experience and afterglow contribute to ketamine’s antidepressant effects and that common questionnaires may not fully capture its phenomenology.

Authors

  • Suresh Muthukumaraswamy
  • Meg Spriggs
  • Rebecca Sumner

Published

Journal of Psychopharmacology
individual Study

Abstract

Background

Ketamine is central to one of the most rapidly growing areas of neuroscientific research into novel treatments for depression. Limited research has indicated that the psychedelic properties of ketamine may play a role in its antidepressant effects.

Aim

The aim of the current study was to explore the psychedelic experiences and sustained impact of ketamine in major depressive disorder.

Methods

In the current study, ketamine (0.44 mg/kg) was administered to 32 volunteers with major depressive disorder in a crossover design with the active-placebo remifentanil, in a magnetic resonance imaging (MRI) environment. The 11-dimension altered states of consciousness questionnaire and individual qualitative interviews were used to capture the acute psychedelic experience. The Montgomery-Asberg Depression Rating Scale and further interviewing explored lasting effects. The second qualitative interview took place ⩾3 weeks post-ketamine.

Results

Greater antidepressant response (reduction in Montgomery-Asberg Depression Rating Scale at 24 h) correlated with the 11-dimension altered states of consciousness dimensions: spirituality, experience of unity, and insight. The first qualitative interview revealed that all participants experienced perceptual changes. Additional themes emerged including loss of control and emotional and mood changes. The final interview showed evidence of a psychedelic afterglow, and changes to perspective on life, people, and problems, as well as changes to how participants felt about their depression and treatments.

Conclusions

The current study provides preliminary evidence for a role of the psychedelic experience and afterglow in ketamine’s antidepressant properties. Reflexive thematic analysis provided a wealth of information on participants’ experience of the study and demonstrated the psychedelic properties of ketamine are not fully captured by commonly used questionnaires.

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Research Summary of 'A qualitative and quantitative account of patient’s experiences of ketamine and its antidepressant properties'

Introduction

Ketamine has emerged as a prominent investigational treatment for rapid-acting antidepressant effects. Earlier clinical work showed rapid symptom reduction in treatment‑resistant depression and, because ketamine produces acute alterations in consciousness, researchers have queried whether the psychedelic properties of ketamine contribute to its antidepressant action. Compared with classic serotonergic psychedelics such as psilocybin, ketamine differs in pharmacology and phenomenology, and prior studies relating ketamine's acute subjective effects to clinical benefit have been inconsistent, in part because typical scales (for example, CADSS or BPRS) emphasise dissociation or psychotomimesis rather than the richer, mystical-like features measured by instruments such as the Altered States of Consciousness (ASC) questionnaire. Sumner and colleagues designed a mixed-methods study to explore the acute psychedelic experience of sub‑anesthetic ketamine and its association with antidepressant response, and to characterise any sustained changes in perspective or mood that persist beyond the immediate therapeutic window. The study combined quantitative measurement using the 11‑dimension ASC (11D‑ASC) and clinician-rated depression scores with two rounds of qualitative interviews conducted shortly after infusion and 3–8 weeks later, using a randomised, double‑blind, active placebo–controlled crossover framework against remifentanil.

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Study Details

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