05 April 2026 : Review article
Ketamine or Esketamine in Special Populations of Patients With Treatment-Resistant Depression
Łukasz Grabarczyk ABCDEFG 1*, Sophia Rebekka Wolfermann AB 2, Hubert Oniszczuk
F 3, Paweł Radkowski ABCDEF 4,5
DOI: 10.12659/MSM.950601
Med Sci Monit 2026; 32:e950601
Table 1 Comparison of ketamine and esketamine [130].
| Aspect | Ketamine | S-ketamine (Esketamine) |
|---|---|---|
| Chemical structure | Racemic mixture of R(−) and S(+) enantiomers | S(+) enantiomer of ketamine |
| Approved use | Anesthetic, analgesic | Anesthetic, analgesic; treatment-resistant depression (Spravato)* |
| Off-label use | Treatment-resistant depression and suicidal ideation | |
| Routes of administration | ||
| Intravenous | 0.5–1.0 mg/kg (over 40–60 min), twice weekly for 2 weeks | |
| Intramuscular | Unvalidated; likely similar to intravenous | |
| Subcutaneous | Unvalidated; likely similar to intravenous | |
| Oral | 100–250 mg, 2–3 times per week | |
| Sublingual | Unvalidated; likely similar to oral | |
| Intranasal | 50–150 mg, twice weekly | 56–84 mg, twice weekly for 4 weeks |
| Transdermal | Unvalidated | |
| Bioavailability after administration | ||
| Intravenous | 100% | |
| Intramuscular | 90–95% | |
| Subcutaneous | 90–95% | |
| Oral | 10–20% | |
| Sublingual | 20–30% | |
| Intranasal | 30–50% | |
| Transdermal | 10–50% | |
| Clinical considerations | Higher likelihood of psychotomimetic adverse effects | Greater potency |
| * Approved in combination with an oral antidepressant after failure of ≥2 prior treatments. | ||