Therapeutic advances in psychopharmacologyFeb 24, 2026

Ketamine's lasting antidepressant effect is linked to increased stress system activity but not feeling detached

Psychedelic Science Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 27, 2026

Abstract

Essence

Higher infusion blood pressure, but not dissociation, was linked to ketamine response at day 7 in patients with depression.

Evidence

This post hoc analysis used an open-label single-infusion ketamine study in 39 patients, comparing hemodynamics, CADSS/BPRS symptoms, drug levels, and MADRS response.

Caveat

The study was small, open-label, and post hoc, so blood pressure and antipsychotic-use signals are associative predictors rather than proven mechanisms.

Simplified

BACKGROUND: Ketamine is a rapid-acting antidepressant with robust evidence, but unclear predictors of therapeutic response.

OBJECTIVES: Based on previous knowledge, hemodynamic parameters and acute altered state of consciousness have been hypothesized as potential correlates of subsequent antidepressant outcome.

DESIGN: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSION: Higher blood pressure during ketamine administration was associated with better antidepressant outcome, supporting the hypothesis concerning 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.

TRIAL REGISTRATION: EudraCT 2018-001539-39.

Key numbers

16.2 mmHg

Increase in Systolic Blood Pressure

Mean difference in SBP between responders and nonresponders at 10 minutes.

12.1 mmHg

Increase in Diastolic Blood Pressure

Mean difference in DBP between responders and nonresponders at 10 minutes.

17 of 39

Response Rate

Number of responders out of total patients treated.

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Ketamine's lasting antidepressant effect is linked to increased stress system activity but not feeling detached

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