Ketamine administered biomedically or as psychedelic-assisted therapy in treatment-resistant depression: Differing efficacy based on depressive subtype or presence of childhood trauma?
Australasian Psychiatry October 13, 2026 DOI: 10.1177/10398562261494440 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Commentary Randomized Open-label Peer reviewed |
|---|---|
| Intervention | Ketamine |
| Measures | Sydney Melancholia Prototypic Index |
| Topics | Depression Esketamine Ketamine Psychedelic-assisted therapy |
| Key points | Argues that ketamine treatment for treatment-resistant depression should be examined through depressive subtypes, and reports preliminary open-label (non-randomized) findings suggesting biomedical ketamine may be superior in melancholic versus non-melancholic depression as subtyped by the Sydney Melancholia Prototypic Index. Notes that studies of ketamine as a psychedelic agent combined with psychotherapy are lacking, and proposes an empirical approach to test differential efficacy by subtype or childhood trauma. |
Abstract
ObjectiveThe ideas presented in this paper are based on a presentation at a festschrift event marking the retirement of Professor Gordon Parker from UNSW, Sydney. Drawing on Gordon's depressive subtyping approach and his critiques of a unitary view of major depressive disorder and treatment-resistant depression (TRD), we aim to (i) explore differing models of ketamine for TRD - biomedical versus 'psychedelic-assisted' therapy, and (ii) whether there may be differential efficacy in each approach based on subtype and/or childhood trauma.ConclusionPreliminary results from our study indicate in an open-label (but not randomised controlled) setting, biomedical ketamine may be superior in melancholic versus non-melancholic depression subtyped using Sydney Melancholia Prototypic Index. Studies of ketamine as a psychedelic agent combined with psychotherapy are lacking. We outline an empirical approach to determine whether ketamine with integrated psychotherapy has differential efficacy based on depressive subtype or past childhood trauma.
In the evidence
This study is part of the evidence base for 2 syntheses in the library. Here is how each one recorded it.
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Argues that ketamine's efficacy should be examined by depressive subtype and childhood trauma, reports preliminary open-label findings that biomedical ketamine may be superior in melancholic depression, and notes that studies of ketamine combined with psychotherapy are lacking.
Synthesized
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Argues that ketamine efficacy should be examined by depressive subtype, reporting preliminary open-label findings that biomedical ketamine may be superior in melancholic versus non-melancholic depression, and notes psychedelic-assisted studies are lacking.
Synthesized
Citations in the library
Cites 10
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
- Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study American Journal of Psychiatry May 21, 2019
- MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial. Nature Medicine October 1, 2023
- Ketamine Assisted Psychotherapy (KAP): Patient Demographics, Clinical Data and Outcomes in Three Large Practices Administering Ketamine with Psychotherapy Journal of Psychoactive Drugs March 15, 2019
- Psilocybin for treatment resistant depression in patients taking a concomitant SSRI medication. Neuropsychopharmacology September 1, 2023
and 5 more in the library