A study published in the Journal of Psychiatric Research indicates that patients with treatment-resistant depression who experienced improvement after subcutaneous esketamine treatment reported higher levels of dissociation compared to those who did not respond. Treatment-resistant depression is defined as depression that does not improve after at least two adequate trials of standard antidepressants. Esketamine, derived from ketamine, is increasingly being recognized as a potential treatment for this condition.
Read More
Originally developed as an anesthetic, ketamine has shown the ability to induce rapid changes in depressive symptoms, albeit with some patients experiencing temporary alterations in consciousness. This can include feelings of detachment from one’s body or thoughts, or viewing the surroundings as unreal or dreamlike, collectively referred to as dissociation. Researchers remain divided on whether dissociation is merely a side effect of ketamine treatment or if it has a role in the drug's antidepressant efficacy.
The study followed 30 adults participating in an open-label clinical trial at Onofre Lopes University Hospital in Brazil, led by Kaike Thiê da C. Gonçalves from the University of São Paulo. Of those, 23 completed all eight treatment sessions and were included in the analysis, which comprised 15 females and eight males with an average age of 34.3 years. Initially, participants received 0.5 milligrams of esketamine per kilogram of body weight, with the possibility of increasing the dose to 0.75 or 1 milligram per kilogram if there was less than a 50% reduction in depressive symptoms.
Depression levels were assessed prior to each treatment and one week following the final session. Dissociation was measured using a clinician-administered questionnaire 40 minutes after each dose. The questionnaire analyzed overall dissociation as well as specific experiences like derealization, depersonalization, and amnesia.
Out of the participants, 12 met the responder criteria, meaning their depression scores decreased by at least 50%. Those who responded to treatment exhibited higher overall dissociation scores than the non-responders. They also reported significantly greater derealization. Although depersonalization and amnesia scores were higher among responders, the differences were not statistically significant.
Interestingly, dissociation levels remained stable throughout the treatment sessions, and no significant relationship was found between an individual's dissociation levels during a particular session and their changes in depression scores. Therefore, while greater dissociation correlated with a higher likelihood of response, an individual’s dissociation level at any given session did not reliably predict their improvement.
The study suggests that dissociative experiences, particularly derealization, may serve as meaningful correlates of antidepressant outcomes. However, the researchers noted that these findings are exploratory and may inform future investigations into the relevance of altered consciousness in treatment outcomes.
Several study limitations were acknowledged, including the absence of a placebo group or blinding, and the lack of control for other medications or psychiatric conditions. Moreover, the increased doses for patients not adequately responding may have influenced dissociation scores, possibly reflecting greater cumulative drug exposure rather than a definitive biological marker of clinical improvement.
The study titled “Dissociation and Antidepressant Response to Subcutaneous Esketamine: A Clinical Study” includes contributions from multiple authors including Vagner Deuel de O. Tavares, Fernanda Palhano-Fontes, and several others.