(Es)ketamine in functional neurological disorder: a systematic review
Bruce Tamilson, Michael Chitolie, Jan Coebergh, Niruj Agrawal, Norman Poole, Matt Butler, Richard Kanaan, Timothy R. Nicholson
Frontiers in Psychiatry July 20, 2026 DOI: 10.3389/fpsyt.2026.1872389 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Case report Peer reviewed |
|---|---|
| Interventions | ketamine esketamine |
| Topics | Esketamine Ketamine |
| Keywords | Functional/dissociative seizures Conversion disorder |
| Key findings | The current evidence base is insufficient to establish the efficacy of (Es)ketamine for functional neurological disorder, though improvements in functional symptoms have been reported across several presentations. |
Abstract
Background and aimFunctional neurological disorder (FND) is a common and disabling condition for which effective treatments remain limited. Clinical outcomes are often variable, particularly in chronic and comorbid presentations. Ketamine and esketamine are increasingly used across a range of neuropsychiatric conditions. This review aimed to synthesise the existing evidence regarding their use in FND.MethodsA systematic review of PubMed, PsycINFO and Google Scholar was conducted up to December 2025. Studies reporting clinical outcomes following (Es)ketamine administration in functional neurological symptoms were included. Owing to substantial clinical and methodological heterogeneity, findings were synthesised narratively.ResultsThirteen studies were identified, predominantly comprising case reports and small case series. Across the included studies, some patients were reported to experience improvement in functional motor symptoms, functional dissociative seizures, and other functional presentations following ketamine or esketamine administration. Interpretation of these findings is limited by the uncontrolled nature of the evidence base, heterogeneity of diagnoses and outcomes, and the potential influence of publication and expectancy bias. Adverse effects were variably reported and were generally described as transient in supervised clinical settings.ConclusionThe current evidence base is limited to predominantly uncontrolled and highly heterogeneous studies and is insufficient to establish the efficacy of (Es)ketamine for FND. Although improvements in functional symptoms have been reported across several FND presentations, it remains unclear whether these reflect direct effects on functional symptoms, indirect benefits arising from psychiatric improvement, or other non-specific therapeutic factors. While no firm conclusions regarding efficacy can be drawn, the existing data suggest that further investigation is justified, and prospective controlled trials are needed to clarify the potential role of (Es)ketamine in FND.
Comparable studies
Other systematic reviews and meta-analyses on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis Depressed patients with suicidal ideation at baseline | 2017 | Systematic review and individual participant data meta-analysis | n = 167 |
| Ketamine use: a review Ketamine users | 2011 | Systematic review | |
| Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression Participants with major depression in placebo-controlled, double-blind, randomized... | 2015 | Systematic review and meta-analysis | |
| Ketamine and postoperative pain – a quantitative systematic review of randomised trials Surgical patients from 25 countries | 2004 | Systematic review | n = 2,839 |
| Side-effects associated with ketamine use in depression: a systematic review. Patients with depression | 2018 | Systematic review |
Citations in the library
Cites 30
- Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation American Journal of Psychiatry March 17, 2021
- Ketamine Assisted Psychotherapy (KAP): Patient Demographics, Clinical Data and Outcomes in Three Large Practices Administering Ketamine with Psychotherapy Journal of Psychoactive Drugs March 15, 2019
- Efficacy and safety of adjunctive therapy using esketamine or racemic ketamine for adult treatment-resistant depression: A randomized, double-blind, non-inferiority study. Journal of Affective Disorders November 14, 2019
- The potential of ketamine for posttraumatic stress disorder: a review of clinical evidence. Therapeutic Advances in Psychopharmacology 2023
- Psychedelic treatment of functional neurological disorder: a systematic review Therapeutic Advances in Psychopharmacology 2020
and 25 more in the library