Ketamine and Esketamine for Suicidal Ideation: A Stratified Evidence Synthesis Across Intravenous, Intranasal, and Injection Routes (2016–2026)
SSRN Electronic Journal preprint DOI: 10.2139/ssrn.6979838 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review and meta-analysis Randomized |
|---|---|
| Sample size | 2,220 |
| Population | Patients with suicidal ideation |
| Interventions | Ketamine Esketamine Buprenorphine |
| Topics | Esketamine Ketamine |
| Key findings | Intravenous ketamine produces rapid, independent anti-suicidal effects within 40 minutes, with 63% full ideation remission by Day 3 versus 32% for placebo. |
Abstract
This white paper reports a stratified evidence synthesis of 31 peer-reviewed studies (2016–2026) examining ketamine and esketamine as rapid-acting treatments for suicidal ideation. Studies were classified by administration route — intravenous racemic ketamine (14 primary studies, N=1,258), intranasal esketamine/Spravato (6 primary studies, N=844), and injection routes combining intramuscular and subcutaneous delivery (4 studies, N=118) — and analyzed using a random-effects model with pre-specified heterogeneity thresholds. The intravenous track yielded moderate heterogeneity (I²=58%) and a high-certainty pooled verdict: IV ketamine produces rapid, independent anti-suicidal effects within 40 minutes, with 63% full ideation remission by Day 3 versus 32% for placebo, extendable through buprenorphine follow-on or maintenance infusion. The intranasal track yielded massive heterogeneity (I²=84%), triggering meta-regression that identified three load-bearing confounders: a hospitalization floor effect masking drug-specific signal in registration trials, single-item measurement insensitivity, and baseline treatment refractoriness. When these confounders are removed — in outpatient settings and CBT-augmented protocols — esketamine's anti-suicidal signal emerges clearly and extends to 18 weeks. The injection track shows promising acute results but lacks randomized controlled trial evidence. The underlying dataset is publicly available on Zenodo (DOI: 10.5281/zenodo.20802538).
Comparable studies
Other systematic reviews and meta-analyses on esketamine, most cited first.