Sympathetic activation but not dissociation linked to ketamine's sustained antidepressant effect.
Veronika Andrashko, Tomáš Novák, Miloslav Kopecek, Anna Šuláková, Vit Knop, Jiří Horáček
Therapeutic Advances in Psychopharmacology 2026 DOI: 10.1177/20451253261419636 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Post hoc analysis of an open-label study Peer reviewed |
|---|---|
| Sample size | 39 |
| Population | Patients with depression |
| Intervention | ketamine |
| Dose | 0.54 mg/kg |
| Duration | Single intravenous infusion, assessed at day 7 |
| Topics | Ketamine Esketamine |
| Keywords | Antidepressant Antipsychotics Blood pressure Dissociation |
| Key points | Higher blood pressure during ketamine infusion predicted better antidepressant response at day 7, while dissociation and psychotomimetic symptoms did not. |
Abstract
Ketamine is a rapid-acting antidepressant with robust evidence, but unclear predictors of therapeutic response. Based on previous knowledge, hemodynamic parameters and acute altered state of consciousness have been hypothesized as potential correlates of subsequent antidepressant outcome. A post hoc analysis was performed using the data from an open-label study, in which 39 patients with depression received a single intravenous infusion of ketamine (0.54 mg/kg). Antidepressant response was defined as ⩾50% reduction in the Montgomery-Åsberg Depression Rating Scale (MADRS) at day 7. Systolic and diastolic blood pressure (SBP and DBP), heart rate, Clinician-Administered Dissociative States Scale (CADSS) and Brief Psychiatric Rating Scale (BPRS) were assessed during the infusion, alongside plasma levels of ketamine and norketamine. Data were analyzed using mixed-effects models and correlation and regression techniques. Responders exhibited significantly higher SBP and DBP during ketamine infusion compared with nonresponders. The degree of dissociation or psychotomimetic symptoms during the infusion did not differ significantly between responders and nonresponders. Antipsychotic (AP) augmentation was associated with worse antidepressant outcome as well as with lower infusion-related blood pressure values. CADSS and BPRS did not differ between AP users and nonusers. None of the parameters correlated with plasma levels of ketamine or norketamine. Higher blood pressure during ketamine administration was associated with better antidepressant outcome, supporting the hypothesis concerning sympathetic activation in treatment responders. Psychological parameters (as measured by CADSS and BPRS) were not linked to subsequent outcomes and did not resolve inconsistencies in previous studies. Concomitant antipsychotic medication attenuated ketamine's antidepressant effects. EudraCT 2018-001539-39.
Comparable studies
Other non-randomized and open-label trials on ketamine, most cited first.
Citations in the library
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and 42 more in the library