(Es)ketamine in functional neurological disorder: a systematic review

Functional neurological disorder (FND) is a common and disabling condition with limited effective treatments. This systematic review synthesized evidence on ketamine and esketamine use in FND. Thirteen studies were identified, mostly case reports and small case series. Some patients showed improvement in functional motor symptoms, functional dissociative seizures, and other presentations after receiving ketamine or esketamine. However, interpretation is limited by uncontrolled study designs, heterogeneous diagnoses and outcomes, and potential publication and expectancy bias. Adverse effects were variably reported but generally transient in supervised settings. The evidence is insufficient to establish efficacy, though the data suggest that further prospective controlled trials are justified.

Study at a glance

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.