Blood pressure elevation with ketamine and esketamine in depression: a systematic review and meta-analysis of randomised trials
Karim Haffar
Open Science Framework November 2, 2026 preprint DOI: 10.17605/osf.io/csarj (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review protocol Randomized |
|---|---|
| Population | Adults with depression, including treatment-resistant depression |
| Interventions | Ketamine Esketamine |
| Topics | Depression Esketamine Ketamine |
| Key findings | The protocol proposes to examine whether ketamine or esketamine, by any route, elevates blood pressure in adults with depression compared with placebo or an active control, with mean change in systolic and diastolic blood pressure as the primary outcome and the proportion with clinically significant hypertension as the secondary outcome. No findings are reported because screening has not started. |
Abstract
Review title: Blood pressure elevation with ketamine and esketamine in depression: a systematic review and meta-analysis of randomised trials Type and method of review: Meta analysis Stage of review at time of this submission: Review ongoing — the protocol has been finalised and the peer-reviewed search prepared; formal screening not yet started. Review question: In Adults with depression (including treatment-resistant depression), what is the effect of Ketamine or esketamine (any route) compared with Placebo or active control on Blood pressure elevation (mean change in systolic and diastolic BP) (primary); proportion with clinically significant hypertension (secondary)? Searches: The following sources will be searched: Europe PMC (PubMed, MEDLINE & preprints), PubMed / MEDLINE, Embase, Cochrane CENTRAL, Scopus, Google Scholar. Additional records may be imported from other databases. No date or language restrictions are applied unless otherwise stated. The search strategy underwent peer review (PRESS) before execution. Condition or domain being studied: Adults with depression (including treatment-resistant depression) Participants / population: Adults with depression (including treatment-resistant depression) Intervention(s), exposure(s): Ketamine or esketamine (any route) Comparator(s) / control: Placebo or active control Types of study to be included: Inclusion criteria: Adults with major depressive disorder or treatment-resistant depression; Ketamine (intravenous, intramuscular, oral) or esketamine (intranasal); Compared with placebo or an active control; Randomised controlled trials reporting blood pressure outcomes; Full-text article published in English. Exclusion criteria: Anaesthetic or analgesic use of ketamine only; Non-randomised studies; Reviews, editorials, letters, case reports or conference abstracts; Overlapping samples (the largest or most recent report is kept) Main outcome(s): Blood pressure elevation (mean change in systolic and diastolic BP) (primary); proportion with clinically significant hypertension (secondary) Data extraction (selection and coding): Two reviewers will independently screen titles/abstracts and full texts, blinded to each other’s decisions, and extract data in duplicate using a standardised, piloted form. Disagreements will be resolved by discussion or a third reviewer. Risk of bias (quality) assessment: The risk of bias of each included study will be assessed independently by two reviewers using a study-design-appropriate tool. Disagreements will be resolved by consensus. Risk of bias in the review itself will be appraised with ROBIS. Strategy for data synthesis: Results will be synthesised narratively. Where studies are sufficiently homogeneous, effect estimates will be pooled in a meta-analysis using a fixed- or random-effects model as indicated by heterogeneity (I²). The certainty of the evidence will be rated using GRADE.
Comparable studies
Other systematic reviews and meta-analyses on esketamine for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Comparative efficacy of racemic ketamine and esketamine for depression: a systematic review and meta-analysis Adults with unipolar or bipolar major depression | 2020 | Systematic review and meta-analysis | n = 1,877 |
| The acute antisuicidal effects of single-dose intravenous ketamine and intranasal esketamine in individuals with major depression and bipolar disorders: A systematic review and meta-analysis. Participants in randomized controlled trials of ketamine for suicidal ideation | 2020 | Systematic review and meta-analysis | n = 197 |
| Efficacy of Esketamine Augmentation in Major Depressive Disorder Patients with major depressive disorder who are treatment-resistant or acutely suicidal | 2020 | Systematic review and meta-analysis | n = 774 |
| Esketamine Treatment for Depression in Adults: A PRISMA Systematic Review and Meta-Analysis. Patients with treatment-resistant major depressive disorder | 2025 | Systematic review and meta-analysis | |
| EFFICACY AND SAFETY OF RACEMIC KETAMINE AND ESKETAMINE FOR DEPRESSION: A SYSTEMATIC REVIEW AND META-ANALYSIS Adults with unipolar or bipolar major depression | 2022 | Systematic review and meta-analysis | n = 2,903 |