Sympathetic activation but not dissociation linked to ketamine's sustained antidepressant effect.
Veronika Andrashko, Tomas Novak, Miloslav Kopecek, Anna Sulakova, Vit Knop, Jiri Horacek
Therapeutic advances in psychopharmacology January 1, 2026 Peer reviewed DOI: 10.1177/20451253261419636 via PubMed
Summary
Higher blood pressure during ketamine administration is linked to better antidepressant outcomes in patients with depression, as those who responded to treatment had significantly higher systolic and diastolic blood pressure compared to nonresponders. However, the degree of dissociation experienced did not differ between groups, and the use of antipsychotic medication was associated with worse outcomes. This suggests that sympathetic activation may play a role in treatment response.
Study at a glance
| Design | post hoc analysis |
|---|---|
| Sample size | 39 |
| Population | patients with depression receiving intravenous ketamine |
| Key finding | Responders to ketamine treatment exhibited significantly higher systolic and diastolic blood pressure during infusion compared to nonresponders. |
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.