Dissociation Was Tied to Better Esketamine Outcomes in a Small Study
Stronger dissociation went with better depression outcomes in a new esketamine study. PsyPost reported the finding from a small Brazilian trial, where patients with higher dissociation scores were the ones more likely to respond. That runs against the common view of dissociation as a side effect to manage. The sample was 23 people, so this is a lead rather than an answer.
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| Key Takeaway | Detail |
|---|---|
| The study | Secondary exploratory analysis of up to eight weekly subcutaneous esketamine doses |
| The sample | 30 patients were eligible and 23 were analyzed, mean age 34.3 years, 65.2% female |
| The measures | CADSS for dissociation, MADRS and BDI-II for depression |
| The finding | Higher dissociation scores, and higher derealization in particular, went with response |
| What did not differ | Depersonalization and amnesia scores did not separate the two groups |
| The limits | No placebo, no blinding, escalating doses, and the authors call it exploratory |
What the Study Did
The work comes from the University of São Paulo and the Federal University of Rio Grande do Norte, with patients treated at University Hospital Onofre Lopes. It appeared in the Journal of Psychiatric Research.
Patients with treatment-resistant depression received up to eight weekly subcutaneous doses of esketamine. Clinicians scored dissociation with the CADSS after each dose.
Depression was tracked with the MADRS and the BDI-II. Responders were patients whose MADRS score fell by at least half from baseline to the end of treatment. About half the group met that bar.
What It Found
Patients who responded had significantly higher total dissociation scores across the treatment period. The p value was 0.024.
The difference was driven by derealization, the sense that the world around a patient is not real. That subscale separated the groups at p equals 0.011.
Two other parts of the experience did not separate the groups. Depersonalization came in at 0.056 and amnesia at 0.089, both short of the usual threshold.
Dissociation scores also stayed stable across the eight sessions rather than fading with repeated dosing.
What It Does Not Show
This is a comparison between two groups of patients. It does not show that a more intense session produces a better week for the same patient.
There was no placebo group and no blinding. Doses escalated during treatment, so intensity and timing move together and cannot be cleanly separated.
The authors are direct about this. They call the findings exploratory and ask for larger, dose-controlled studies before anyone draws clinical conclusions.
One Route Note for US Clinics
The esketamine here was given subcutaneously. In the United States, esketamine reaches patients as Spravato, an intranasal spray delivered under REMS monitoring.
Subcutaneous dosing is used in research settings in Brazil and elsewhere. Results from that route do not transfer directly to a Spravato program or to an IV ketamine protocol.
Why Clinicians Are Arguing About This
The answer decides what a good session looks like. If dissociation is noise, the goal is relief with as little of it as possible. If it is signal, a quiet session may be an underdosed one.
It also shapes products. Formulations designed for minimal dissociation, including an oral capsule with promising early data, are built on the assumption that the experience is separable from the benefit.
Evidence has pointed both ways. A pain study found that stronger dissociation did not mean better pain relief, and receptor work suggests more than one brain system may be involved.
What to Do With It Now
Nothing about dosing should change on the strength of 23 patients. The practical move is measurement.
Clinics that already score CADSS during monitoring can pair those scores with depression scales at set intervals. That turns an open question into something a practice can look at in its own records.
It is also a reason to keep describing the experience carefully to patients. The therapeutic role of the session is still unsettled, as our look at ketamine assisted psychotherapy evidence found.
Patients looking for supervised care can start with our directory of verified ketamine clinics.
This article is for informational purposes and is not medical advice. The study described is early, exploratory research and does not change current treatment practice.
