Intravenous esketamine in pediatric Rett syndrome: An open-label, early phase 1 pilot study.
Huiping Li, Shu Liu, Caimei Lin, Yuchao Wu, Xiuping Wu, Yukun Huang, Yajun Wu, Xiubin Tong, Xiu Xu
Molecular therapy. Methods & clinical development March 13, 2025 DOI: 10.1016/j.omtm.2025.101413 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Pilot study Open-label Peer reviewed |
|---|---|
| Sample size | 3 |
| Population | Girls with classic Rett syndrome aged 5-10 years |
| Intervention | Esketamine |
| Duration | 5 weeks (once per week for 5 weeks) |
| Topics | Esketamine |
| Keywords | N-methyl-d-aspartate receptor antagonist Rett syndrome Efficiency Safety Medical research Neurology treatment Pediatric medicine Rare diseases Drug therapy |
| Citations | 5 |
| Key points | Intravenous esketamine was generally well tolerated and showed minimal improvements in behavioral and motor assessments in three girls with Rett syndrome. |
Abstract
Rett syndrome (RTT) is a severe neurodevelopmental disorder. N-Methyl-d-aspartate receptor (NMDAR) antagonism has shown therapeutic potential in preclinical RTT models. We performed a pilot study to explore whether intravenous esketamine, an NMDAR antagonist, alleviates the symptoms of pediatric RTT. This was a prospective, single-arm, single-site, open-label, early phase 1 pilot study. Three girls with classic RTT aged 5-10 years were enrolled. Esketamine was intravenously administrated once per week for 5 weeks. The efficacy assessments included RTT-related questionnaires and video electroencephalograms (VEEGs). Prespecified adverse events (AEs) were monitored using clinical observations and standard laboratory tests. The treatment with intravenous esketamine was generally well tolerated and safe, with some patients experiencing mild AEs, including self-alleviating nausea, vomiting, and irritability. Three participants showed minimal improvements in their Clinical Global Impression Scale-Improvement, Rett Syndrome Behavior Questionnaire, and Revised Motor Behaviors Assessment Scale scores. However, individual differences were observed in the efficacy measures. VEEGs indicated gradual increases in posterior dominant rhythm peak frequency throughout the intervention. This pilot study highlights the potential of esketamine treatment for improving behavioral dysfunction in patients with RTT. Investigating the appropriate dosage form of esketamine may enhance its beneficial effects in RTT with fewer undesirable features.
Comparable studies
Other non-randomized and open-label trials on esketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Esketamine Nasal Spray Plus Oral Antidepressant in Patients With Treatment-Resistant Depression Adults (≥ 18 years) with treatment-resistant depression | 2020 | Phase 3, open-label, multicenter, long-term study | n = 802 |
| Long-Term Safety and Maintenance of Response With Esketamine Nasal Spray in Participants With Treatment-Resistant Depression: Interim Results of the SUSTAIN-3 Study Adults with treatment-resistant depression | 2023 | Open-label, long-term extension study | n = 1,148 |
| Safety and efficacy with esketamine in treatment-resistant depression: long-term extension study. Adults with treatment-resistant depression who participated in ≥1 of 6 phase 3 parent... | 2025 | Open-label, single-arm long-term extension study | n = 1,148 |
| Efficacy and Safety of Intranasal Esketamine in Patients With Treatment-Resistant Depression and Comorbid Chronic Post-traumatic Stress Disorder: Open-Label Single-Arm Pilot Study Patients with treatment-resistant major depressive disorder and comorbid post-traumatic... | 2022 | Open-label, single-arm, retrospective pilot study | n = 11 |
| Managing Esketamine Treatment Frequency Toward Successful Outcomes: Analysis of Phase 3 Data Patients with treatment-resistant depression | 2020 | Post-hoc analysis of an open-label, long-term study | n = 778 |
Citations in the library
Cited by 3
- Esketamine Exposure Affects Neurodevelopment and Glutamate-NMDAR Signaling in Zebrafish Larvae. Journal of Biochemical and Molecular Toxicology May 1, 2026
- Effect of the Preoperative Application of Esketamine on Stress Indicators in Paediatric Patients Undergoing Bronchoalveolar Lavage Under General Anaesthesia. British journal of hospital medicine (London, England : 2005) June 25, 2025
- Therapeutic potential of classic and non-classic psychedelics in neurodevelopmental disorders: Opportunities and challenges Pharmacological Research August 26, 2026
Cites 7
- Intravenous Esketamine in Adult Treatment-Resistant Depression: A Double-Blind, Double-Randomization, Placebo-Controlled Study Biological Psychiatry November 4, 2015
- Molecular mechanisms underlying the antidepressant actions of arketamine: beyond the NMDA receptor Molecular Psychiatry May 7, 2021
- Ketamine in neuropsychiatric disorders: an update. Neuropsychopharmacology January 2024
- Oral ketamine may offer a solution to the ketamine conundrum Psychopharmacology December 1, 2023
- N-Methyl-D-Aspartate Receptors, Ketamine, and Rett Syndrome: Something Special on the Road to Treatments? Biological Psychiatry May 1, 2016
and 2 more in the library